Screening of 1.17 million newborns for inborn errors of metabolism using tandem mass spectrometry in Shanghai, China: A 19-year report.

BACKGROUND: Inborn errors of metabolism (IEMs) frequently result in progressive and irreversible clinical consequences if not be diagnosed or treated timely. The tandem mass spectrometry (MS/MS)-based newborn screening (NBS) facilitates early diagnosis and treatment of IEMs. The aim of this study was to determine the characteristics of IEMs and the successful deployment and application of MS/MS screening over a 19-year time period in Shanghai, China, to inform national NBS policy. METHODS: The amino acids and acylcarnitines in dried blood spots from 1,176,073 newborns were assessed for IEMs by MS/MS. The diagnosis of IEMs was made through a comprehensive consideration of clinical features, biochemical performance and genetic testing results. The levels of MS/MS testing parameters were compared between various IEM subtypes and genotypes. RESULTS: A total of 392 newborns were diagnosed with IEMs from January 2003 to June 2022. There were 196 newborns with amino acid disorders (50.00%, 1: 5910), 115 newborns with organic acid disorders (29.59%, 1: 10,139), and 81 newborns with fatty acid oxidation disorders (20.41%; 1:14,701). Phenylalanine hydroxylase deficiency, methylmalonic acidemia and primary carnitine deficiency were the three most common disorders. Some hotspot variations in eight IEM genes (PAH, SLC22A5, MMACHC, MMUT, MAT1A, MCCC2, ACADM, ACAD8), 35 novel variants and some genotype-biochemical phenotype associations were identified. CONCLUSIONS: A total of 28 types of IEMs were identified, with an overall incidence of 1: 3000 in Shanghai, China. Our study offered clinical guidance for the implementation of MS/MS-based NBS and genetic counseling for IEMs in this city.

A high-quality assembled genome of a representative peach landrace, 'Feichenghongli', and analysis of distinct late florescence and narrow leaf traits.

BACKGROUND: Peach (Prunus persica L. Batsch) is one of the most popular fruits worldwide. Although the reference genome of 'Lovell' peach has been released, the diversity of genome-level variations cannot be explored with one genome. To detect these variations, it is necessary to assemble more genomes. RESULTS: We sequenced and de novo assembled the genome of 'Feichenghongli' (FCHL), a representative landrace with strict self-pollination, which maintained the homozygosity of the genome as much as possible. The chromosome-level genome of FCHL was 239.06 Mb in size with a contig N50 of 26.93 Mb and only 4 gaps at the scaffold level. The alignment of the FCHL genome with the reference 'Lovell' genome enabled the identification of 432535 SNPs, 101244 insertions and deletions, and 7299 structural variants. Gene family analysis showed that the expanded genes in FCHL were enriched in sesquiterpenoids and triterpenoid biosynthesis. RNA-seq analyses were carried out to investigate the two distinct traits of late florescence and narrow leaves. Two key genes, PpDAM4 and PpAGL31, were identified candidates for the control of flower bud dormancy, and an F-box gene, PpFBX92, was identified as a good candidate gene in the regulation of leaf size. CONCLUSIONS: The assembled high-quality genome could deepen our understanding of variations among diverse genomes and provide valuable information for identifying functional genes and improving the molecular breeding process.

Construction of Co2 P-Ni3 S2 /NF Heterogeneous Structural Hollow Nanowires as Bifunctional Electrocatalysts for Efficient Overall Water Splitting.

Designing efficient and stable transition metal-based catalysts for electrocatalytic water splitting is vital for the development of hydrogen production. Herein, a facile synthetic strategy is developed to fabricate transition metal-based heterogeneous structural Co2 P-Ni3 S2 hollow nanowires supported on nickel foam (Co2 P-Ni3 S2 /NF). Owing to the multiple active sites provided by transition metal compounds, large surface area of the unique hollow nanowire morphology, and the synergistic effect of Co2 P-Ni3 S2 heterostructure interfaces, Co2 P-Ni3 S2 /NF requires ultralow overpotentials of 110, 164 mV for HER and 331.7, 358.3 mV for OER at large current densities of 100, 500 mA cm-2 in alkaline medium, respectively. Importantly, the two-electrode electrolyzer assembled by Co2 P-Ni3 S2 /NF displays a cell voltage of 1.54 V at 10 mA cm-2 and operates stably over 24 h at 100 mA cm-2 , which performs better than reported transition metal-based bifunctional electrocatalysts. This work presents a successful fabrication of transition metal-based bifunctional HER/OER electrocatalysts at large-current density and brings new inspiration for developing applicable energy conversion materials.

Clinical characteristics and genotypes of 201 patients with mucopolysaccharidosis type II in China: A retrospective, observational study.

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage disease caused by a disease-associated variant in the IDS gene, which encodes iduronate 2-sulfatase (IDS). We aimed to characterize the clinical characteristics and genotypes of the largest cohort of Chinese patients with MPS II and so gain a deeper understanding of natural disease progression. Patients with confirmed MPS II and without treatment were included. The disease was classified as severe in patients with neurological impairment, and as attenuated in patients aged >6 years without neurological impairment. Of the 201 male patients, 78.1% had severe MPS II. Cognitive regression occurred before age 6 years in 94.3% of patients. Of 122 IDS variants identified, 37 were novel. Among the large gene alteration types identified, only the frequency of IDS-IDS2 recombination was significantly higher in severe versus attenuated MPS II (P = 0.032). Some identified point variants could inform the understanding of genotype-phenotype correlations. In conclusion, this study showed that classification of the disease as attenuated should only be made in patients aged >6 years. Our findings expand the understanding of the genotype-phenotype relationship, inform the diagnostic process, and provide an indication of the likely prognosis.

Body temperature and infection in critically ill patients on continuous kidney replacement therapy.

PURPOSE: Continuous kidney replacement therapy (CKRT) is an increasingly common intervention for critically ill patients with kidney failure. Because CKRT affects body temperature, detecting infections in patients on CKRT is challenging. Understanding the relation between CKRT and body temperature may facilitate earlier detection of infection. METHODS: We retrospectively reviewed adult patients (≥ 18 years) admitted to the intensive care unit at Mayo Clinic in Rochester, Minnesota, from December 1, 2006, through November 31, 2015, who required CKRT. We summarized central body temperatures for these patients according to the presence or absence of infection. RESULTS: We identified 587 patients who underwent CKRT during the study period, of whom 365 had infections, and 222 did not have infections. We observed no statistically significant differences in minimum (P = .70), maximum (P = .22), or mean (P = .55) central body temperature for patients on CKRT with infection vs. those without infection. While not on CKRT (before CKRT initiation and after cessation), all three body temperature measurements were significantly higher in patients with infection than in those without infection (all P < .02). CONCLUSION: Body temperature is insufficient to indicate an infection in critically ill patients on CKRT. Clinicians should remain watchful for other signs, symptoms, and indications of infection in patients on CKRT because of expected high infection rates.

Mucopolysaccharidosis type IIIC in chinese mainland: clinical and molecular characteristics of ten patients and report of six novel variants in the HGSNAT gene.

BACKGROUND: Mucopolysaccharidosis type IIIC (MPS IIIC; Sanfilippo syndrome C) is a rare lysosomal storage disease caused by mutations in the heparan-α-glucosaminide N-acetyltransferase (HGSNAT) gene, resulting in the accumulation of heparan sulfate. MPS IIIC is characterized by severe neuropsychiatric symptoms and mild somatic symptoms. METHODS: Our study analyzed the clinical presentation and biochemical characteristics of ten Chinese MPS IIIC patients from eight families. Whole exome sequencing was applied to identify the variants in HGSNAT gene. In one patient with only one mutant allele identified firstly, whole genome sequencing was applied. The pathogenic effect of novel variants was evaluated in silico. RESULTS: The mean age at the onset of clinical symptoms was 4.2 ± 2.5 years old, and the mean age of diagnosis was 7.6 ± 4.5 years old, indicating a delay of diagnosis. The most common onset symptoms were speech deterioration, and the most frequent presenting symptoms are speech deterioration, mental deterioration, hyperactivity and hepatomegaly, sequentially. All mutant alleles of 10 patients have been identified. There were eleven different HGSNAT variants, and the most common one was a previously reported variant c.493 + 1G > A. There were six novel variants, p.R124T, p.G290A, p.G426E, c.743 + 101_743 + 102delTT, c.851 + 171T > A and p.V582Yfs*18 in our cohort. Extraordinarily, two deep intron variants were identified in our cohort, with the variant c.851 + 171T > A identified by whole genome sequencing. CONCLUSION: This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients, which would assist in the early diagnosis and genetic counselling of MPS IIIC.

Discrepancy between perceptions and acceptance of clinical decision support Systems: implementation of artificial intelligence for vancomycin dosing.

BACKGROUND: Artificial intelligence (AI) tools are more effective if accepted by clinicians. We developed an AI-based clinical decision support system (CDSS) to facilitate vancomycin dosing. This qualitative study assesses clinicians' perceptions regarding CDSS implementation. METHODS: Thirteen semi-structured interviews were conducted with critical care pharmacists, at Mayo Clinic (Rochester, MN), from March through April 2020. Eight clinical cases were discussed with each pharmacist (N = 104). Following initial responses, we revealed the CDSS recommendations to assess participants' reactions and feedback. Interviews were audio-recorded, transcribed, and summarized. RESULTS: The participants reported considerable time and effort invested daily in individualizing vancomycin therapy for hospitalized patients. Most pharmacists agreed that such a CDSS could favorably affect (N = 8, 62%) or enhance (9, 69%) their ability to make vancomycin dosing decisions. In case-based evaluations, pharmacists' empiric doses differed from the CDSS recommendation in most cases (88/104, 85%). Following revealing the CDSS recommendations, we noted 78% (69/88) discrepant doses. In discrepant cases, pharmacists indicated they would not alter their recommendations. The reasons for declining the CDSS recommendation were general distrust of CDSS, lack of dynamic evaluation and in-depth analysis, inability to integrate all clinical data, and lack of a risk index. CONCLUSION: While pharmacists acknowledged enthusiasm about the advantages of AI-based models to improve drug dosing, they were reluctant to integrate the tool into clinical practice. Additional research is necessary to determine the optimal approach to implementing CDSS at the point of care acceptable to clinicians and effective at improving patient outcomes.

Pentagalloyl Glucose: A Review of Anticancer Properties, Molecular Targets, Mechanisms of Action, Pharmacokinetics, and Safety Profile.

Pentagalloyl glucose (PGG) is a natural hydrolyzable gallotannin abundant in various plants and herbs. It has a broad range of biological activities, specifically anticancer activities, and numerous molecular targets. Despite multiple studies available on the pharmacological action of PGG, the molecular mechanisms underlying the anticancer effects of PGG are unclear. Here, we have critically reviewed the natural sources of PGG, its anticancer properties, and underlying mechanisms of action. We found that multiple natural sources of PGG are available, and the existing production technology is sufficient to produce large quantities of the required product. Three plants (or their parts) with maximum PGG content were Rhus chinensis Mill, Bouea macrophylla seed, and Mangifera indica kernel. PGG acts on multiple molecular targets and signaling pathways associated with the hallmarks of cancer to inhibit growth, angiogenesis, and metastasis of several cancers. Moreover, PGG can enhance the efficacy of chemotherapy and radiotherapy by modulating various cancer-associated pathways. Therefore, PGG can be used for treating different human cancers; nevertheless, the data on the pharmacokinetics and safety profile of PGG are limited, and further studies are essential to define the clinical use of PGG in cancer therapies.

Investigation of GALNS variants and genotype-phenotype correlations in a large cohort of patients with mucopolysaccharidosis type IVA.

Mucopolysaccharidosis type IVA (MPS IVA) is a rare autosomal recessive disorder resulting from the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) caused by pathogenic variants in the GALNS gene. A systematic analysis for genotype-phenotype correlation is essential due to hundreds of variants generating different levels of residual GALNS activity and causing a wide degree of clinical manifestation effects. Here, we retrospectively analyzed clinical and genetic data of 108 unrelated patients with MPS IVA to investigate the variants spectrum of GALNS and assess their clinical effects. In this cohort, 82 patients were classified as severe, 14 as intermediate, and 12 as mild. One hundred and one GALNS variants were identified, of which 47 were novel. Most patients with at least one GALNS null variant were classified as severe phenotype (92%, 33/36). Missense variants mapped to different residues of GALNS protein resulted in different phenotypes in patients with MPS IVA. Ninety-two percent of patients with two missense variants mapped to buried residues were classified as severe (92%, 24/26), while at least one missense variant mapped to surface residues was identified in patients with biallelic missense variants presenting intermediate MPS IVA (78%, 7/9) and presenting mild MPS IVA (86%, 6/7). Our study contributes to a better understanding of the molecular spectrum of GALNS variants and their clinical implications. Based on the data herein reported, we generated a systematic flowchart correlating the GALNS variants to assist in phenotype prediction and classification of patients with MPS IVA.

Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.

Niemann-Pick disease Types A and B (NPA/B) are autosomal recessive disorders caused by variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. This study aimed to describe and characterize a cohort of 118 patients diagnosed with NPA/B based on clinical, biochemical, and molecular findings, and to identify sound correlations between laboratory findings and clinical presentations. Decreased peripheral leukocyte acid sphingomyelinase activity levels and increased plasma 7-ketocholesterol levels were significantly correlated with disease onset and severity of the clinical course. We identified 92 different sequence SMPD1 variants, including 41 novel variants, in 118 NPA/B patients (19 NPA, 24 intermediate type, 75 NPB). The most prevalent mutation was p.Arg602His, which accounted for 9.3% of the alleles. Patients homozygous for p.Arg602His or p.Asn522Ser showed a late-onset form of the NPB phenotype. The homozygous SMPD1 variant p.Tyr500His correlated with the early-onset NPB clinical form. Additionally, homozygous variants p.His284SerfsX18, p.Phe465Ser, and p.Ser486Arg were associated with the neuronopathic NPA clinical form. The homozygous variant p.Arg3AlafsX74 was associated with the intermediate clinical form. Our study contributes to the understanding of the natural history of NPA/B and assists in the development of efficacious treatments for patients afflicted with this devastating lysosomal storage disorder.

Simultaneous Use of Hypertonic Saline and IV Furosemide for Fluid Overload: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the efficacy of the simultaneous hypertonic saline solution and IV furosemide (HSS+Fx) for patients with fluid overload compared with IV furosemide alone (Fx). DATA SOURCES: Electronic databases (MEDLINE, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, and WOS) were searched from inception to March 2020. STUDY SELECTION: Randomized controlled trials on the use of HSS+Fx in adult patients with fluid overload versus Fx were included. DATA EXTRACTION: Data were collected on all-cause mortality, hospital length of stay, heart failure-related readmission, along with inpatient weight loss, change of daily diuresis, serum creatinine, and 24-hour urine sodium excretion from prior to post intervention. Pooled analysis with random effects models yielded relative risk or mean difference with 95% CIs. DATA SYNTHESIS: Eleven randomized controlled trials comprising 2,987 acute decompensated heart failure patients were included. Meta-analysis demonstrated that HSS+Fx was associated with lower all-cause mortality (relative risk, 0.55; 95% CI, 0.46-0.67; p < 0.05; I2 = 12%) and heart failure-related readmissions (relative risk, 0.50; 95% CI, 0.33-0.76; p < 0.05; I2 = 61%), shorter hospital length of stay (mean difference, -3.28 d; 95% CI, -4.14 to -2.43; p < 0.05; I2 = 93%), increased daily diuresis (mean difference, 583.87 mL; 95% CI, 504.92-662.81; p < 0.05; I2 = 76%), weight loss (mean difference, -1.76 kg; 95% CI, -2.52 to -1.00; p < 0.05; I2 = 57%), serum sodium change (mean difference, 6.89 mEq/L; 95% CI, 4.98-8.79; p < 0.05; I2 = 95%), and higher 24-hour urine sodium excretion (mean difference, 61.10 mEq; 95% CI, 51.47-70.73; p < 0.05; I2 = 95%), along with decreased serum creatinine (mean difference, -0.46 mg/dL; 95% CI, -0.51 to -0.41; p < 0.05; I2 = 89%) when compared with Fx. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from low to moderate. CONCLUSIONS: Benefits of the HSS+Fx over Fx were observed across all examined outcomes in acute decompensated heart failure patients with fluid overload. There is at least moderate certainty that HSS+Fx is associated with a reduction in mortality in patients with acute decompensated heart failure. Factors associated with a successful HSS+Fx utilization are still unknown. Current evidence cannot be extrapolated to other than fluid overload states in acute decompensated heart failure.

Identification of predominant GNPTAB gene mutations in Eastern Chinese patients with mucolipidosis II/III and a prenatal diagnosis of mucolipidosis II.

Mucolipidosis II α/ß, mucolipidosis III α/ß, and mucolipidosis III γ are autosomal recessive disorders belonging to the family of lysosomal storage disorders caused by deficiency of the UDP-N-acetylglucosamine, a lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) localized in the Golgi apparatus, which is essential for normal processing and packaging of soluble lysosomal enzymes with initiating the first step of tagging lysosomal enzymes with mannose-6-phosphate (M6P). Mucolipidosis II and III are caused by mutations in the GNPTAB and GNPTG genes, and patients with these diseases are characterized by short stature, skeletal abnormalities, and developmental delay. In this study we report 38 patients with mucolipidosis II and III enrolled in Eastern China during the past 8 years. The diagnosis was made based on clinical characteristics and measurement of plasma lysosomal enzyme activity. Sanger sequencing of GNPTAB and/or GNPTG for all patients and real-time quantitative PCR were performed to confirm the diagnosis. In addition, 11 cases of prenatal mucolipidosis II were diagnosed based on measurement of the enzyme activity in amniotic fluid supernatant and genetic testing of cultured amniotic cells. Based on molecular genetic tests, 30 patients were diagnosed with mucolipidosis II α/ß, 6 were diagnosed with III α/ß and 2 were diagnosed with III γ. Thirty-seven different GNPTAB gene mutations were identified in 29 patients with mucolipidosis II α/ß and six patients with III α/ß. These mutations included 22 new mutations (p.W44X, p.E279X, p.W416X, p.W463X, p.Q802X, p.Q882X, p.A34P, p.R334P, p.D408N, p.D534N, p.Y997C, p.D1018V, p.L1025S, p.L1033P, c.88_89delAC, c.890_891insT, c.1150_1151insTTA, c.1523delG, c.2473_2474insA, c.2980_2983delGCCT, c.3094delA, and deletion of exon 9). Four new GNPTG gene mutations were identified (c.13delC, p.Y81X, p.G126R and c.609+1delG) in two mucolipidosis III γ patients. Among the 11 cases of prenatal diagnosis, four were mucolipidosis II fetuses, three were heterozygous, and the remaining four were normal fetuses. This study expands the mutation spectrum of the GNPTAB and GNPTG genes and contributes to specific knowledge of mucolipidosis II/III in a population from Eastern China.

Biochemical, molecular and outcome analysis of eight chinese asymptomatic individuals with methyl malonic acidemia detected through newborn screening.

Methyl malonic academia (MMA) is characterized by abnormal accumulation of methyl malonic acid in body fluids. Patients usually have a variety of clinical symptoms including recurrent vomiting, metabolic acidosis, developmental delay, seizure, or death. However, a few cases where the patients have no symptom are also reported. Here, we conducted clinical, biochemical, and molecular analysis of eight Chinese patients identified through newborn screening between 2003 and 2013. All the patients had significantly higher blood propionylcarnitine (C3) concentrations, ratio of propionylcarnitine/acetylcarnitine (C3/C2); and their urine methyl malonic acid and methylcitric acid (MCA) excretions were remarkably higher than normal at diagnosis and during follow-ups. In addition, five different known mutations were identified in seven of the eight patients in either MUT or MMACHC. All these mutations were expected to produce defective proteins that would result in decreased or even total loss of methyl malonyl-CoA mutase activity. However, normal outcomes were found in all patients in physical growth, intellectual performance and cerebral MRI analysis at diagnosis (range, 14-53 days) and during follow-ups (range, 1.8-10 years). Our study is the first report of Chinese MMA patients with increased secretion of methyl malonic acid and molecular defects in MUT or MMACHC yet remain asymptomatic.

Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

BACKGROUND: Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. METHODS: Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. RESULTS: Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. CONCLUSIONS: In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants.

[Clinical characteristics and analysis of mass spectrometric data in patients with ornithine transcarbamylase deficiency].

OBJECTIVE: To explore the clinical manifestations and biochemical characteristics of patients with ornithine transcarbamylase deficiency (OTCD) so as to increase the clinician awareness for this disease. METHODS: The clinical manifestations, blood ammonia levels, citrulline levels, urinary orotic acid and uracil levels were analyzed for 40 patients with OTCD from 2005 to 2013. And comparisons were made with 25 healthy children. RESULTS: Among them, the median age of onset was 1.4 years (3 days-29 years). The major clinical manifestations were feeding difficulties, persistent vomiting, convulsions, unconsciousness and hyperammonemia, etc. The blood levels of citrulline in these patients were significantly lower than those of the control group (6.35 (1.84-21.11) vs 13.65 (10.23-24.52) µmol/L, P < 0.05) . The urinary levels of orotic acid and uracil in these patients were significantly higher than those in the control group (167.77 (1.21-1 650.45) vs 0.25 (0-2.32) mmol/molCr, 52.67 (3.50-338.64) vs 0.69 (0-2.87) mmol/molCr, P < 0.05) . CONCLUSION: For patients with hyperammonemia, the decreased levels of citrulline in blood tested by tandem mass spectrometry and increased orotic acid and uracil in urine on gas chromatography-mass spectrometry may aid the diagnosis OTCD.

The scientometric characteristics of cheilitis researched by multidisciplinary specialists: A comparative study.

Background/purpose: Cheilitis is a relatively common lip disease with many etiologies and causes including concomitant mucocutaneous or systemic diseases, which needs multidisciplinary communication. The purpose of this study was to compare the scientometric characteristics of cheilitis publications by multidisciplinary specialists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into three groups (dermatologists, stomatologists, and other scholars). Results: There were 478 and 241 papers on cheilitis published by dermatologists and stomatologists, respectively. The total citation count was 5838 and the h index was 36 for cheilitis publications by dermatologists, and the total count was 2983 and the h index was 27 for cheilitis publications by stomatologists. Interestingly, we observed that dermatologists preferentially concerned contact cheilitis/dermatitis and plasma cell cheilitis, while stomatologists preferentially concerned cheilitis-related lip neoplasms including squamous cell carcinoma, dysplasia, and precancerous conditions. The most common disorder researched by both dermatologists and stomatologists was actinic cheilitis. The keywords such as patch test, cosmetic, edema, drug efficacy, toothpaste, lipstick, allergens, and granulomatous inflammation were common in dermatologists' publications; while the keywords such as protein expression, metabolism, risk factor, prevalence, malignant transformation, and carcinogenesis were common in stomatologists' publications. Conclusion: This study for the first time reported the scientometric characteristics of cheilitis as an interdisciplinary disease researched by specialists. It highlights that cheilitis-related specialists through reciprocal collaboration and communication will improve the patients' outcomes.

SPINK1 is a Potential Diagnostic and Prognostic Biomarker for Sepsis.

Purpose: There are no satisfactory diagnostic biomarkers for sepsis. Accordingly, this study screened biomarkers valuable for sepsis diagnosis and prognosis using data-independent acquisition (DIA) combined with clinical data analysis. Patients and Methods: Serine protease inhibitor Kazal-type 1 (SPINK1) is a differentially expressed protein that was screened using DIA and bioinformatics in sepsis patients (n = 22) and healthy controls (n = 10). The plasma SPINK1 levels were detected using an enzyme-linked immunosorbent assay (ELISA) in an expanded population (sepsis patients, n = 52; healthy controls, n = 10). The diagnostic value of SPINK1 in sepsis was evaluated using receiver operating characteristic (ROC) curve analysis based on clinical data. The prognostic value of SPINK1 for sepsis was evaluated using correlation and survival analyses. Results: DIA quality control identified 78 differential proteins (72 upregulated and six downregulated), among which SPINK1 was highly expressed in sepsis. The ELISA results suggested that SPINK1 expression was significantly elevated in the sepsis group (P < 0.05). ROC analysis of SPINK1 yielded an area under the curve (AUC) of 0.9096. Combining SPINK1 with procalcitonin (PCT) for ROC analysis yielded an AUC of 1. SPINK1 expression was positively correlated with the Sequential Organ Failure Assessment (SOFA) score (r = 3497, P = 0.0053) and APACHE II score (r = 3223, P = 0.0106). High plasma SPINK1 protein expression was negatively correlated with the 28-day survival rate of patients with sepsis (P = 0.0149). Conclusion: The plasma of sepsis patients contained increased SPINK1 protein expression. Combining SPINK1 with PCT might have a high diagnostic value for sepsis. SPINK1 was associated with the SOFA score, APACHE II score, and the 28-day survival rate in patients with sepsis.

Knowledge, attitude, and practice towards bacterial multidrug-resistance and structural equation modeling analysis among intensive care unit nurses and physicians.

BACKGROUND: The intensive care unit (ICU) is a department with a high risk of MDR bacteria, and ICU nurses and physicians play critical roles in bacterial multidrug resistance (MDR) prevention. OBJECTIVES: To explore the knowledge, attitudes, and practice (KAP) towards bacterial MDR among ICU nurses and physicians. METHODS: A self-designed questionnaire was administered to collect data. Structural equation modeling (SEM) was applied to assess the associations among study variables. RESULTS: A total of 369 questionnaires were collected; 43 questionnaires were excluded due to self-contradictory on the trap question or the obviously repeated pattern. Finally, 326 (88.35%) valid questionnaires were included in the analysis. The knowledge, attitudes, and practice were 13.57 ± 1.69 (90.47%, possible range: 0-15), 38.75 ± 2.23 (96.88%, possible range: 8-40), and 47.40 ± 3.59 (94.80%, possible range: 10-50). The SEM showed that knowledge had a direct effect on attitude with a direct effect value of 0.61 (P < 0.001) and a direct negative effect on practice with a direct effect value of -0.30 (P = 0.009). The direct effect of attitude on practice was 0.89 (P < 0.001); the indirect effect of knowledge through attitude on practice was 0.52 (P < 0.001). Job satisfaction had a direct effect on attitude and practice, with an effect value of 0.52 (P = 0.030) and 0.75 (P = 0.040). Being a physician (OR = 0.354, 95%CI: 0.159-0.790, P = 0.011), 5-9.9 years of practice (OR = 4.534, 95%CI: 1.878-8.721, P < 0.001), and ≥ 10 years of practice (OR = 3.369, 95%CI: 1.301-8.721, P = 0.012) were independently associated with good knowledge. The attitude scores (OR = 1.499, 95%CI: 1.227-1.830, P < 0.001), male gender (OR = 0.390, 95%CI: 0.175-0.870, P = 0.022), and 5-9.9 years of experience (OR = 0.373, 95%CI: 0.177-0.787, P = 0.010) were independently associated with proactive practice. CONCLUSION: Nurses and physicians in the ICU showed good knowledge, positive attitudes, and proactive practice toward bacterial MDR. Nurses and physicians' knowledge had a direct effect on their attitude, while attitude might directly influence the practice and also play a mediating role between knowledge and practice. Job satisfaction might directly support the positive attitude and practice toward bacterial MDR.

An interpretable machine learning model for predicting 28-day mortality in patients with sepsis-associated liver injury.

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction.