Humans ; Arthritis, Psoriatic/drug therapy* ; Interleukin-17 ; Interleukin Inhibitors ; Antirheumatic Agents/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Interleukin-23/therapeutic use*

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

BACKGROUND:Studies have shown that nucleotide binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,interleukin-18,and interleukin-1β levels can induce an inflammatory cascade response to release inflammatory factors,affect metabolic stress,and damage endothelial cells involved in the development and progression of diabetic foot ulcers,which can provide a reference for early infections. OBJECTIVE:To investigate the predictive effect of peripheral blood mononuclear cell NLRP3 inflammasome,interleukin-18 and interleukin-1β levels on early infection after flap repair of diabetic foot ulcers. METHODS:A total of 147 patients with diabetic foot ulcers were selected and divided into infection group and non-infection group according to whether they were infected within 1 week after operation.Logistic regression was used to analyze the relationship between NLRP3 inflammasome,interleukin-18 and interleukin-1β levels in peripheral blood mononuclear cells and early postoperative infections,and to evaluate their predictive values. RESULTS AND CONCLUSION:In 147 patients with diabetic foot ulcers,35 cases(23.81%)were infected within 1 week after operation,and 47 strains of pathogenic bacteria were isolated,including 25 strains of Gram-positive bacteria(53.19%)and 22 strains of Gram-negative bacteria(46.81%).Univariate analysis showed that Wagner grade,presence of comorbid diabetic nephropathy,operation time,peripheral blood NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,interleukin-18 and interleukin-1β levels were risk factors for early postoperative infections(all P＜0.05).Multivariate analysis suggested that Wagner grade,NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,high interleukin-18,interleukin-1β were independent risk factors(all P＜0.05).Receiver operator characteristic curve results showed that the area under the receiver operator characteristic curve of NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,interleukin-18 and interleukin-1β for early postoperative infections in patients with diabetic foot ulcers was 0.823,0.705,0.676,0.811 and 0.853,respectively,and the area under the curve of combined predictive efficacy was 0.915.To conclude,patients with diabetic foot ulcers are mainly affected by Gram-positive bacteria,and the levels of NLRP3 inflammasome,interleukin-18 and interleukin-1β in peripheral blood mononuclear cells are independent risk factors for early postoperative infections.The combined prediction efficacy of these indicators is better and deserves further in-depth study.

BACKGROUND:This study aims to explore whether Xuebijing(XBJ)can improve intestinal microcirculation dysfunction in sepsis and its mechanism. METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ+axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate)were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(P13K),phosphorylated P13K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt)in the small intestine was analyzed via Western blotting. RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total P13K,and p-Akt/total Akt in the rat small intestine. CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

Brucellosis,a worldwide epidemic bacterial zoonotic infectious disease caused by bacteria of the genus Brucella,jeopardizes livestock production and poses a major threat to public health safety.Among the various components of Brucella,the outer membrane proteins play crucial roles as the primary immune and protective antigens.These proteins are closely asso-ciated with Brucella's virulence,regulation of the immune response,and ability to survive and multiply within host cells.This article summarizes recent research progress in the primary outer membrane proteins of Brucella,and offers a synthesized view of the current knowledge landscape.Understanding the antigenic characteristics of Brucella outer membrane proteins may sub-stantially contribute to the establishment of new diagnostic methods and the design of new vaccines,thus potentially leading to more effective prevention strategies against brucellosis.The review provides a reference for future studies and may aid in brucel-losis control efforts.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Background::Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year 2050.Methods::Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (<55 years and ≥55 years), country, world region, and level of Human Development Index (HDI) for 185 countries. The predicted incidence and mortality burden for 2050 was calculated based on demographic projections.Results::In 2022, an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred worldwide. The age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were higher in women (ASIR: 13.60 per 100,000; ASMR: 0.53 per 100,000) than in men (ASIR: 4.60 per 100,000; ASMR: 0.35 per 100,000). The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes, with relatively similar ASMR across regions. Among 185 countries, China had the largest number of TC cases (accounting for 56.77% of total cases) and TC-related deaths (accounting for 24.35% of global TC-related deaths), with the highest ASIR in men (13.30 per 100,000). Worldwide, approximately 64.63% of TC cases occurred in populations under 55 years old, while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and above. If the rates stay the same as in 2022, it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050, indicating a 34.15% and 89.58% increase, respectively.Conclusions::TC is a highly frequent cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.