Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

OBJECTIVE To establish a ultra-high-performance liquid chromatography-mass spectrum/mass spectrum(UPLC-MS/MS) method for the determination of anlotinib in human plasma and assessment of clinical application. METHODS Zanubrutinib was used as internal standard and the extraction process was performed through protein precipitation method using acetonitrile, followed by separation on an Ultimate XB-C18(100 mm×2.1 mm, 3.0 μm) column using acetonitrile and 10 mmol·L−1 ammonium acetate-0.1% formic acid step-elution gradient. The flow rate was 0.6 mL·min−1 and injection volume was 5 μL. The mass analysis was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, and the mass spectrometer was set at m/z 408.1→339.1 for anlotinib and m/z 472.2→290.1 for internal standard, respectively. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability of the method and clinical application were investigated. RESULTS The method was validated over the concentration range of 1.0−100.0 ng·mL−1, with R2=0.998 4. The precision RSD was<9%, the recovery and matrix effect were 104.81%−107.32% and 102.54%−105.26%, respectively, and this method had good stability and was not affected by matrix effect. The method had been used for determined 52 advanced non-small cell lung cancer patients treated with anlotinib. The trough plasma concentration (Ctrough) was measured on day 43 after initiation of anlotinib treatment. Anlotinib Ctrough were higher than lower limit of quantitation (1.0 ng·mL−1) from 52 patients. The plasma concentration of anlotinib Ctrough was (11.38±4.29)ng·mL−1 with 37.66% coefficients of variation, which were shown large inter-patient variability. CONCLUSION This method is high sensitivity, specificity and accurate, and suitable for determination of anlotinib in human plasma.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Objective : To analyze the clinical characteristics of patients with abdominal type allergic purpura(HSP), to improve their diagnostic level, and to explore the risk factors for gastrointestinal bleeding in HSP patients. Methods : A retrospective analysis was conducted on the clinical manifestations, laboratory data, imaging, endoscopic, and pathological characteristics of 98 patients with abdominal type HSP. Based on the occurrence of gastrointestinal bleeding, 98 patients were divided into a bleeding group and a non-bleeding group, and the risk factors for gastrointestinal bleeding in HSP patients were analyzed. Results : Abdominal HSP often presented with abdominal pain, vomiting, vomiting blood, black stools, and bloody stools. Imaging often showed edema and thickening of the duodenum and jejunum, as well as enlargement of surrounding lymph nodes. Under endoscopy, the descending part of the duodenum and jejunum mucosa were commonly congested and edematous with erosion, and ulcers were seen in the distal ileum. Pathology commonly involved acute and chronic inflammation of the mucosa with congestion, edema, and local erosion. Patients with gastrointestinal bleeding had significantly higher levels of white blood cell count(WBC), neutrophil count(NEUT), C-reactive protein(CRP), D-dimer(D-D), and fibrinolytic products(FDP) compared to non-bleeding patients(P<0.05), while levels of red blood cell count(RBC), hemoglobin(HGB), and albumin(ALB) were significantly lower than those of non bleeding patients(P<0.05). Logistic regression analysis showed that decreased ALB and increased FDP were independent risk factors for gastrointestinal bleeding in patients with abdominal HSP(P<0.05). The areas under the ROC curves of ALB and FDP were(AUC=0.877, 95%CI:0.794-0.960,P<0.01) and(AUC=0.806, 95%CI:0.722-0.890,P<0.01), respectively. The maximum value of the Jordan index for ALB was 0.734, with sensitivity and specificity of 89.6% and 83.9%, respectively, and had a critical value of 38.2 g/L. The maximum value of the Jordan index for FDP was 0.577, with sensitivity and specificity of 64.2% and 93.5%, respectively, and had a critical value of 18.14 μg/ml. There was no statistically significant difference in the ROC curves between ALB and FDP. Conclusion For HSP with abdominal pain as the initial symptom, imaging and endoscopic examination are helpful for early diagnosis. Decreased ALB and elevated FDP are independent risk factors for gastrointestinal bleeding in adult patients with abdominal HSP.

Objective To explore the correlation between the variability of blood potassium level and risk of renal insufficiency(RI)in elderly heart failure(HF)patients with chronic systolic dys-function.Methods A total of 157 consecutive elderly patients with chronic HF admitted in De-partment of Cardiovascular Medicine of Wuhu First People's Hospital from January 2020 to No-vember 2022 were included,and according to whether RI occurred or not,they were divided into the RI group(36 cases)and the non-RI group(121 cases).Their general data and blood potassium variability was collected and recorded,and all of them were followed up for 6 months.Multivariate logistic regression analysis was applied for the correlation between blood potassium variability and RI in the elderly patients with chronic HF.Results The range of change,maximum fluctuation rate and coefficient of variation for blood potassium were significantly higher in the RI group than the non-RI group(P＜0.01).Multivariate logistic regression analysis showed that length of hospi-tal stay(OR=1.174,95％CI:1.067-1.292,P=0.001),age(OR=1.939,95％CI:1.309-2.872,P=0.001),albumin level(OR=0.866,95％CI:0.751-0.997,P=0.046),and range of change(OR=1.774,95％CI:1.519-2.071,P=0.016),maximum fluctuation rate(OR=1.631,95％CI:1.265-2.167,P=0.001)and coefficient of variation of blood potassium(OR=1.670,95％CI:1.212-2.230,P=0.002)were independent influencing factor for RI in the patients.Logistic re-gression analysis indicated that the range of serum potassium change≥0.80,the maximum fluctu-ation rate ≥0.40,and the coefficient of variation of serum potassium ≥8.20 were closely correla-ted with RI in elderly patients with chronic HF(P＜0.01).Conclusion High variability of blood potassium level is a risk factor for RI in elderly patients with chronic HF.

OBJECTIVE To explore the application of HL60-pNL3.2 reporter gene assay in pyrogen detection of live attenuated varicella vaccine, inactivated influenza vaccine and lyophilized live attenuated hepatitis A vaccine. METHODS According to the publication draft named as "in vitro pyrogen test(reporter gene assay)" in Chinese Pharmacopoeia, maximum valid dilution(MVD) of three kinds of vaccines was calculated, and the interference test was conducted to explore whether these vaccines interfere with the pyrogen determination. According to the general rule 9101 from Chinese Pharmacopoeia 2020, the assay in the pyrogen detection of the three vaccines was validated, using the methods to determine the pyrogen content of three vaccines. RESULTS The MVD of live attenuated varicella vaccine, inactivated influenza vaccine and lyophilized live attenuated hepatitis A vaccine respectively were 1 000, 200 and 1 000 times. The recovery rates of endotoxin(LPS) in the three kinds of vaccine were between 52.5% and 110.1%. The methodological validation results showed that the method could be used for the determination of pyrogens in three vaccines, and the correlation coefficient(R2) between LPS concentration and its chemical light intensity(RLU value) was > 0.98, the recovery rates were between 76.4% and 192.8% when LPS concentration was between 1 and 250 EU·mL–1. The coefficient of variation of measured results was less than 25% when LPS concentration was more than 5 EU·mL–1. The limit of detection and the limit of quantitation were between 0.05 and 0.13 EU·mL–1. Then, the pyrogen of these vaccines was determined by HL60-pNL3.2 reporter gene assay, and the pyrogen concentration all was less than contaminant limit concentration. CONCLUSION HL60-pNL3.2 reporter gene assay has the advantages of no animal, simple and rapid operation, with wide pyrogen spectrum and can quantitative pyrogen, which can be used to detect pyrogen of live attenuated varicella vaccine, inactivated influenza vaccine and lyophilized live attenuated hepatitis A vaccine.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Amino acid surfactants (AAS) have excellent properties such as low toxicity,antibacterial,mildness,and corrosion resistance. In recent years,they have been widely applied in the field of daily chemicals,food and pharmaceutical industry. It is pointed out that the structure at molecular level largely affects the physical and chemical properties of AAS materials. In this work,the structures of solid-state N-lauroyl-L-alanine (NLLA) including intermolecular interactions,molecular local dynamics and molecular assembly were investigated by a variety of solid-state nuclear magnetic resonance (SSNMR) techniques. Based on 2D 1H-1H double quantum-single quantum (2D 1H-1H DQ-SQ),1H-1H DQ sideband pattern and molecular simulation,it was found that there was a stable intermolecular hydrogen bond formed between the carboxyl units of two NLLA molecules. Combined with the study of 2D frequency switched Lee—Goldberg heteronuclear correlation (2D 13C-1H FSLG-HETCOR) and 13C T1,another type of hydrogen bond was probed,which existed between amide units of neighboring molecules. In addition,the conformation of alkyl chain ends was investigated. According to 1D 13C{1H}cross polarization/magic angle spinning (CP/MAS) and 2D 13C-1H FSLG-HETCOR spectra,it was revealed that the alkyl-chain ends had both gauche and trans conformations. Moreover,the trans conformation showed two distinct 13C chemical shifts,originated from two NLLA molecular assembly forms. Accordingly,two NLLA molecular assembly structures were suggested which were transoid form and cisoid form. This work provided a SSNMR investigation strategy for characterizing the molecular local structure and dynamics of AAS materials,which helped task of researching and developing materials with improved chemical and physical properties.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]