Detecting pulmonary malignancy against benign nodules using noninvasive cell-free DNA fragmentomics assay.

BACKGROUND: Early screening using low-dose computed tomography (LDCT) can reduce mortality caused by non-small-cell lung cancer. However, ∼25% of the 'suspicious' pulmonary nodules identified by LDCT are later confirmed benign through resection surgery, adding to patients' discomfort and the burden on the healthcare system. In this study, we aim to develop a noninvasive liquid biopsy assay for distinguishing pulmonary malignancy from benign yet 'suspicious' lung nodules using cell-free DNA (cfDNA) fragmentomics profiling. METHODS: An independent training cohort consisting of 193 patients with malignant nodules and 44 patients with benign nodules was used to construct a machine learning model. Base models using four different fragmentomics profiles were optimized using an automated machine learning approach before being stacked into the final predictive model. An independent validation cohort, including 96 malignant nodules and 22 benign nodules, and an external test cohort, including 58 malignant nodules and 41 benign nodules, were used to assess the performance of the stacked ensemble model. RESULTS: Our machine learning models demonstrated excellent performance in detecting patients with malignant nodules. The area under the curves reached 0.857 and 0.860 in the independent validation cohort and the external test cohort, respectively. The validation cohort achieved an excellent specificity (68.2%) at the targeted 90% sensitivity (89.6%). An equivalently good performance was observed while applying the cut-off to the external cohort, which reached a specificity of 63.4% at 89.7% sensitivity. A subgroup analysis for the independent validation cohort showed that the sensitivities for detecting various subgroups of nodule size (<1 cm: 91.7%; 1-3 cm: 88.1%; >3 cm: 100%; unknown: 100%) and smoking history (yes: 88.2%; no: 89.9%) all remained high among the lung cancer group. CONCLUSIONS: Our cfDNA fragmentomics assay can provide a noninvasive approach to distinguishing malignant nodules from radiographically suspicious but pathologically benign ones, amending LDCT false positives.

Dietary sodium sulphate supplementation during mid-to-late gestation improves placental angiogenesis, bile acid metabolism, and serum amino acid concentrations of sows.

Sulphate plays a vital role in the growth and development of the foetus. Sodium sulphate (Na2SO4) is utilised as a dietary protein nutrient factor and helps replenish sulphur elements in livestock and poultry. Therefore, this study aimed to investigate the effects of Na2SO4 supplementation in mid to late pregnancy on bile acid metabolism, amino acid metabolism, placental vascular development and antioxidant capacity of sows. At day 1 of gestation (G1), a total of twenty-six primiparous sows were carefully chosen and randomised into two groups: (1) control group, (2) Na2SO4 group (1.40 g/kg). Blood samples and placentas from sows were collected to measure biochemistry parameters, antioxidant indexes, placental vascular density, and indicators related to bile acid metabolism and amino acid concentrations, respectively. We found that dietary supplementation with Na2SO4 had a tendency for a reduction of incidence of stillborn at farrowing. Further observation showed that sows supplemented with Na2SO4 had decreased total bile acid level in cord blood, and increased placental gene expression of sulphotransferase and organic anion transport peptide. Na2SO4 supplementation increased catalase and total superoxide dismutase activity in cord blood, decreased placental malondialdehyde content, and enhanced placental protein expression of Sirtuin 1. Moreover, Na2SO4 consumption resulted in increased vascular density of placental stroma and elevated amino acid levels in sows and cord blood. Furthermore, maternal Na2SO4 consumption reduced serum urea concentrations of sows and umbilical cord blood at G114. In addition, dietary supplementation with Na2SO4 activated the protein expression of the placental mechanistic target of rapamycin complex 1. Collectively, these findings indicated that maternal supplementation with Na2SO4 during mid-to-late gestation elevated foetal survival via improving placental angiogenesis, bile acid metabolism and amino acid utilisation.

[Analysis of genetic etiology of 234 deaths in the pediatric intensive care unit with suspected genetic diseases].

Objective: To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics. Methods: This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children's Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson's chi-square test or Fisher's exact probability method were used to compare the clinical characteristics between the groups. Results: A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions: Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.

[Advances in the use of bevacizumab for the treatment of respiratory papilloma].

Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.

[Clinical, imaging, and pathological characteristics of 35 cases of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome].

Objective: To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to improve the diagnosis of this rare disease. Methods: A retrospective case series was conducted to collect the clinical data and results of genetic testing, muscle biopsy, and imaging studies including computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) of 35 patients with MELAS admitted to the Nanjing Drum Tower Hospital from 2012 to 2021. Descriptive statistical analysis including mean, standard deviation, and frequency percentage were carried out. Results: The average age of onset of the patients was 30.2±2.3 years; the prevalence of family history was 20%. The two main initial symptoms were limb weakness and convulsions. The clinical manifestations of the neuromuscular system were proximal muscle weakness and exercise intolerance. The endocrine system is the most affected outside the neuromuscular system, with diabetes being the most common condition. Among the five patients who underwent brain CT, four showed hypodense lesions and two had calcified lesions. Brain MRI in 26 patients showed that the lesions more often affected the parietal lobe, basal ganglia, temporal lobe, occipital lobe, and frontal lobe than the infratentorial areas. Twelve of these individuals exhibited different levels of brain atrophy. Among the 10 patients who underwent 1H-MRS, nine showed a decrease in N-acetylaspartate (NAA) levels, eight exhibited abnormal lactate elevation (Lac peaks), whereas six had both reduced NAA levels and the presence of Lac peaks. Thirty-one patients underwent genetic testing; among them, 25 were found to have the mt.3243A>G mutation, while the remaining six exhibited rare gene alterations. Muscle biopsies were performed in 21 patients, and 15 showed abnormal mitochondrial proliferation manifested by ragged red fibers and defective oxidative phosphorylation manifested by cytochrome C oxidase (COX) enzyme-deficient muscle fibers. Conclusion: The clinical manifestations of MELAS syndrome are variable and complex, and early atypical symptoms could be missed or misdiagnosed. A detailed clinical history, imaging MRS analysis, muscle biopsy, and genetic testing are necessary to confirm the accurate diagnosis of MELAS.

[Biological threats to global malaria elimination II Deletion in the malaria rapid diagnostic test target Plasmodium falciparum histidine-rich protein 2/3 genes].

The global malaria epidemic is still severe. Because of simple procedures, rapid detection and accuracy results, rapid diagnostic test (RDT) has become the most important and the most widely used diagnostic tool for malaria prevention and control. However, deletions in the RDT target Plasmodium falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes may cause false-negative results of RDT, which has been included as one of the four biological threats to global malaria elimination. This article reviews the applications of RDT in the global malaria diagnosis, analyzes the threats and challenges caused by Pfhrp2/3 gene deletion, proposes methods for monitoring Pfhrp2/3 gene deletion, and summarizes the causes and countermeasures of negative RDT detections, so as to provide insights into consolidation of malaria elimination achievements in China and contributions to global malaria elimination.

[Advances in the detection of arousal in obstructive sleep apnea].

Obstructive sleep apnea (OSA) is primarily characterized by intermittent nocturnal hypoxia and sleep fragmentation. Arousals interrupt sleep continuity and lead to sleep fragmentation, which can lead to cognitive dysfunction, excessive daytime sleepiness, and adverse cardiovascular outcome events, making arousals important for diagnosing OSA and reducing the risk of complications, including heart disease and cognitive impairment. Traditional arousal interpretation requires sleep specialists to manually score PSG recordings throughout the night, which is time consuming and has low inter-specialist agreement, so the search for simple, efficient, and reliable arousal detection methods can be a powerful tool to clinicians. In this paper, we systematically reviewed different methods for recognizing arousal in OSA patients, including autonomic markers (pulse conduction time, pulse wave amplitude, peripheral arterial tone, heart rate, etc.) and machine learning-based automated arousal detection systems, and found that autonomic markers may be more beneficial in certain subgroups, and that deep artificial networks will remain the main research method for automated arousal detection in the future.

[Exploration of the clinical transformation application of the artificial intelligence diagnosis system for bladder cancer based on cystoscopy].

This study aims to explore the possibility and bottleneck of clinical translation for an artificial intelligence (AI) diagnosis system for bladder cancer based on cystoscopy.We retrospectively collected videos of 101 bladder cancer patients from January to November 2023, at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among these patients, with a median age of 63 years and 81.0% were male. The bladder cancer AI diagnosis system was utilized for diagnosis, and the accuracy of diagnoses from the videos was assessed. Additionally, a surgical evaluation scale was formulated to evaluate the quality of the videos, simulating clinical usage.The final test results showed a system sensitivity of 97.8%, a positive predictive value of 81.7%, specificity of 54.2%, and a negative predictive value of 92.3%. Furthermore, the surgical evaluation scale scores ranged from 3.96 to 4.69, indicating the feasibility of clinical application for this system.This study further quantitatively validated the accuracy of an artificial intelligence system using cystoscopy videos and assessed the potential for clinical application.

[Investigation on the cognitive level of Mpox among MSM population in Shenzhen and analysis of the influencing factors in 2023].

From June 16 to 30, 2023, men who have sex with men (MSM) who had visited Voluntary Counseling Testing (VCT) clinics in the Luohu, Futian and Nanshan districts of Shenzhen were included in this study to analyze their awareness of Mpox and the influencing factors. The mean age of the 262 MSM was (34.78±8.94) years, with the majority being unmarried (75.2%) and 79.0% confirmed to be infected with HIV. The awareness rates for five primary indicators, current status of Mpox, pathogen and source of infection, mode of transmission, population susceptibility, clinical manifestations and treatment were 68.4%, 84.7%, 60.3%, 87.8%, and 52.5%, respectively. The awareness rates for five secondary indicators, earliest transmission location (44.7%), main mode of transmission (54.2%), role of masks (46.9%), drug accessibility (46.6%), and self-limiting nature (38.2%) were all below 60%. The MSM population in Shenzhen perceived their likelihood of being infected (2.76±1.32) and discriminated against (3.87±1.26) as relatively low. The logistic analysis showed that the high school or vocational school education (OR:3.094, 95%CI:1.180-9.299), college or above education (OR:5.360, 95%CI:2.159-15.501), and higher scores on questions affecting learning or work (OR:2.196, 95%CI:1.409-3.599) were promoting factors for Mpox awareness, while higher scores on questions concerning the possibility of Mpox mortality (OR:0.591, 95%CI:0.432-0.791) was the hindering factor for Mpox awareness.

[Clinical characteristics and surgical management outcomes of glaucoma secondary to congenital ectropion uveae: a preliminary analysis of penetrating Schlemm's canaloplasty].

Objective: To investigate the clinical characteristics and treatment outcomes of glaucoma secondary to congenital ectropion uveae (CEU) using penetrating Schlemm's canaloplasty. Methods: This was a retrospective case series study. Medical records of patients diagnosed with glaucoma secondary to CEU and undergoing penetrating Schlemm's canaloplasty at the Eye Hospital of Wenzhou Medical University between August 2020 and December 2021 were collected. Clinical characteristics including the extent and location of iris ectropion, type of glaucoma, were analyzed. Follow-up visits were conducted at 1, 3, 6 months, and 1 year postoperatively. Visual acuity, intraocular pressure (IOP), anterior segment and fundus condition, filtering bleb morphology, use of IOP-lowering medications, ultrasound biomicroscopy results, and other indicators were analyzed to summarize surgical outcomes. Results: Six cases (6 eyes) of glaucoma secondary to CEU were included, all unilateral, with 3 left eyes and 3 right eyes; median age was 10.0 (5.3, 28.8) years; including 3 males and 3 females. Preoperative IOP was (31.7±10.0) mmHg (1 mmHg=0.133 kPa), and the preoperative number of IOP-lowering medications used was 2.0 (2.0, 3.2). The extent of iris ectropion in the 6 cases ranged from 270 ° to 360 °, with peripheral anterior synechiae corresponding to the location of iris ectropion, and angle closure with the degree of synechiae extending beyond Schwalbe's line. No surgical complications occurred in any of the 6 cases postoperatively. At 1 month postoperatively, the IOP was (16.4±3.2) mmHg, with a median of 0.0 (0.0, 1.5) medications used. At 3 months postoperatively, the IOP was (14.8±6.0) mmHg, with a median of 0.0 (0.0, 2.2) medications used. At 6 months postoperatively, the IOP was (18.1±6.1) mmHg, with a median of 0.0 (0.0, 0.5) medications used. Among them, 5 patients had a follow-up period of 1 year postoperatively, all achieving controlled IOP without the use of IOP-lowering medications, with an average IOP of (15.5±3.1) mmHg. No obvious filtering bleb formation was observed at the surgical site in all patients. Conclusions: Glaucoma secondary to CEU manifests primarily as closed-angle glaucoma, with a correspondence between the closure range of anterior iris adhesions in the angle and the extent of iris ectropion. Penetrating Schlemm's canaloplasty demonstrates favorable and stable efficacy for its treatment.

Associations of ambient temperature and total cloud cover during pregnancy with newborn vitamin D status.

OBJECTIVES: We aimed to estimate the effects of temperature and total cloud cover before birth on newborn vitamin D status. STUDY DESIGN: Prospective birth cohort. METHODS: This study included 2055 mother-newborn pairs in Wuhan, Hubei province, China. The data of temperature and total cloud cover from 30 days before birth were collected, and cord blood 25-hydroxyvitamin D [25(OH)D] were determined. Restricted cubic spline regression models, multiple linear regression models, and logistic regression models were applied to estimate the associations. RESULTS: A "J" shaped curve was observed between temperature and vitamin D status, and an inverse "J" shaped curve was observed between total cloud cover and vitamin D status. Compared to the fourth quartile (75-100th percentile, Q4) of average temperature (30 days before birth), the odds ratio (OR) for Q1 (0-25th percentile) associated with the vitamin D deficiency occurrence (<20 ng/mL) was 3.63 (95% CI, 1.54, 8.65). Compared to Q1 of the average total cloud cover (30 days before birth), the OR associated with the occurrence of vitamin D deficiency was 2.38 (95% CI, 1.63, 3.50) for the Q4. CONCLUSIONS: Low temperature and high cloud cover before delivery were significantly associated with an increased probability of vitamin D deficiency in newborns. The findings suggested that pregnancy women lacking sufficient sunlight exposure still need vitamin D supplement to overcome the potential vitamin D deficiency status.

[Effect of SHP-1 knockout in airway epithelial cells on emphysema phenotype in chronic obstructive pulmonary disease in mice].

Objective: To construct and characterize conditional Src homology region 2 protein tyrosine phosphatase 1 (SHP-1) knockout mice in airway epithelial cells and to observe the effect of defective SHP-1 expression in airway epithelial cells on the emphysema phenotype in chronic obstructive pulmonary disease (COPD). Methods: To detect the expression of SHP-1 in the airway epithelium of COPD patients. CRISPR/Cas9 technology was used to construct SHP-1flox/flox transgenic mice, which were mated with airway epithelial Clara protein 10-cyclase recombinase and estrogen receptor fusion transgenic mice (CC10-CreER+/+), and after intraperitoneal injection of tamoxifen, airway epithelial SHP-1 knockout mice were obtained (SHP-1flox/floxCC10-CreER+/-, SHP-1Δ/Δ). Mouse tail and lung tissue DNA was extracted and PCR amplified to discriminate the genotype of the mice; the knockout effect of SHP-1 gene in airway epithelial cells was verified by qRT-PCR, Western blotting, and immunofluorescence. In addition, an emphysema mouse model was constructed using elastase to assess the severity of emphysema in each group of mice. Results: Airway epithelial SHP-1 was significantly downregulated in COPD patients. Genotyping confirmed that SHP-1Δ/Δ mice expressed CC10-CreER and SHP-1-flox. After tamoxifen induction, we demonstrated the absence of SHP-1 protein expression in airway epithelial cells of SHP-1Δ/Δ mice at the DNA, RNA, and protein levels, indicating that airway epithelial cell-specific SHP-1 knockout mice had been successfully constructed. In the emphysema animal model, SHP-1Δ/Δ mice had a more severe emphysema phenotype compared with the control group, which was manifested by disorganization of alveolar structure in lung tissue and rupture and fusion of alveolar walls to form pulmonary alveoli. Conclusions: The present study successfully established and characterized the SHP-1 knockout mouse model of airway epithelial cells, which provides a new experimental tool for the in-depth elucidation of the role of SHP-1 in the emphysema process of COPD and its mechanism.

[The influencing factors on the spinal sagittal alignment and global balance status of degenerative thoracolumbar kyphosis].

Objective: To explore the effect of degenerative thoracolumbar kyphosis (DTLK) on the sagittal alignment of the spine, as well as the impact on spinal parameters and imbalance secondary to thoracolumbar kyphosis. Methods: A case-control study. A total of 128 DTLK patients who aged over 50 years [thoracolumbar kyphosis (TLK)>15°] treated in Peking University People's Hospital from January 2018 to December 2021 (DTLK group) were retrospectively included in this study. Other 73 contemporaneous patients with lumbar spinal stenosis or disc herniation without thoracolumbar kyphosis (TLK=0°±15°) were enrolled into the control group. The following parameters were obtained on spine X-ray: TLK, thoracic kyphosis (TK), lumbar lordosis (LL) and sagittal vertical axis (SVA). In addition, the osteoporosis (OP) was evaluated by dual-emission X-ray absorptiometry (DXA), and the L5/S1 disc signal grading (Pfirrmann grading) was evaluated on MRI. Based on the age, the Lafage formula SVA=2× (age-55)+25 was used to distinguish balance/imbalance, and the DTLK patients were divided into balanced and an imbalanced group, the characteristics and influencing factors of the loss of sagittal balance in this population were clarified, and the interaction among various parts of the spine under a state of balance was analyzed too. Results: The TK (30.0°±13.5° vs 24.2°±7.4°) and TLK (26.6°±9.7° vs 6.0°±6.6°) in the DTLK group were both larger than those in control group while LL was smaller (34.4°±17.7° vs 44.2°±10.3°) (all P<0.001). TK was correlated to TLK (r=0.234, P=0.008) and LL (r=0.539, P<0.001) in DTLK group. LL loss was positively correlated to L5/S1 disc signal reduction (r=0.253, P=0.044). LL loss [RR=1.04(1.01-1.08)] and OP [RR=3.97(1.09, 14.50)] were influencing factors for the occurrence of imbalance in DTLK patients. The influencing factors for TK in DTLK balance group were LL (ß=0.572, P<0.001) and age (ß=0.351, P=0.045). The positive influencing factor for TK in imbalanced group is LL (ß=0.209, P=0.015), and the impact is weaker than balanced group. Conclusions: Loss of LL and osteoporosis are more likely to cause imbalance and kyphosis in DTLK patients. In DTLK balance group, the proximal spine is regulated by lumbar spine, and the synergistic effect between the two parts maintains balance.

A high resolution reaction microscope with universal two-region time-focusing method.

This paper presents a novel reaction microscope designed for ion-atom collision investigations, established at the Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China. Its time-of-flight (TOF) spectrometer employs an innovative flight-time focusing method consisting of two acceleration regions, providing optimal time focusing conditions for charged fragments with diverse initial velocities. The TOF spectrometer's axis intentionally tilts by 12° relative to the ion beam direction, preventing potential obstructions from the TOF grid electrodes. The introduced focusing method allows for a flexible time-focusing TOF spectrometer design without restricting the length ratio of the two regions. In addition, this configuration in our case significantly suppresses noise on the recoil ion detector produced by residual gas in the ion beam trajectory, which is a considerable challenge in longitudinal spectrometers. In a test experiment on the single electron capture reaction involving 62.5 keV/u He2+ ions and a helium atomic beam, the recoil longitudinal momentum resolution achieved 0.068 atomic units. This novel configuration and successful test run show excellent precision for ion-atom collision studies.

Elevated venous lactate level as an early predictive marker of organ failure in acute pancreatitis: a retrospective study.

OBJECTIVE: The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP). PATIENTS AND METHODS: Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups. RESULTS: Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820. CONCLUSIONS: In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure.

Characterisation of the mitochondrial genome and phylogenetic analysis of Toxocara apodemi (Nematoda: Ascarididae).

We first sequenced and characterised the complete mitochondrial genome of Toxocara apodeme, then studied the evolutionary relationship of the species within Toxocaridae. The complete mitochondrial genome was amplified using PCR with 14 specific primers. The mitogenome length was 14303 bp in size, including 12 PCGs (encoding 3,423 amino acids), 22 tRNAs, 2 rRNAs, and 2 NCRs, with 68.38% A+T contents. The mt genomes of T. apodemi had relatively compact structures with 11 intergenic spacers and 5 overlaps. Comparative analyses of the nucleotide sequences of complete mt genomes showed that T. apodemi had higher identities with T. canis than other congeners. A sliding window analysis of 12 PCGs among 5 Toxocara species indicated that nad4 had the highest sequence divergence, and cox1 was the least variable gene. Relative synonymous codon usage showed that UUG, ACU, CCU, CGU, and UCU most frequently occurred in the complete genomes of T. apodemi. The Ka/Ks ratio showed that all Toxocara mt genes were subject to purification selection. The largest genetic distance between T. apodemi and the other 4 congeneric species was found in nad2, and the smallest was found in cox2. Phylogenetic analyses based on the concatenated amino acid sequences of 12 PCGs demonstrated that T. apodemi formed a distinct branch and was always a sister taxon to other congeneric species. The present study determined the complete mt genome sequences of T. apodemi, which provide novel genetic markers for further studies of the taxonomy, population genetics, and systematics of the Toxocaridae nematodes.

[Marked improvement in rheumatoid lung nodules after treatment with tocilizumab combined with glucocorticoids and leflunomide: a case report and literature review].

Rheumatoid arthritis (RA), a chronic autoimmune disorder, is characterized by erosive inflammation of bone and cartilage, leading to progressive joint destruction. Pulmonary involvement occurs in approximately 60% of RA patients, manifests most commonly as interstitial lung disease and, less commonly, as rheumatoid lung nodules. Here, we report a 50-year-old woman, non-smoker, with recurrent cough and sputum of 7 years' duration, accompanied by a chest CT showing multiple cavitary nodules in both lungs. She had been treated empirically at several medical centers and was finally diagnosed with rheumatoid lung nodules. Marked improvement in rheumatoid lung nodules was observed after treatment with tocilizumab in combination with glucocorticoids and leflunomide. The aim of this study was to improve clinicians' understanding of rheumatoid lung nodules by analyzing the clinical features, diagnosis, and treatment of this case, and reviewing the relevant medical literature.

Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.