[The clinical characteristics of 497 children with congenital pseudarthrosis of the tibia].

Objective: To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center. Methods: This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children with CPT who were treated at Department of Orthopedics, the Children's Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t-test or χ2 tests. Results: Among 497 children with CPT, there were 305 males (61.4 %) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6 %). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157);χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) (χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 cases (63.3%), followed by type Ⅱ in 100 cases (19.7%), type Ⅲ in 54 cases (10.7 %) and type Ⅰ in 32 cases (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 cases (2.8 %), in the middle third in 185 cases (36.5 %), and in the distal third in 308 cases (60.8 %). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range: 0 to 12 surgeries); 76 children (15.3 %) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases), refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times;t=14.93,P<0.01). Conclusions: Crawford type Ⅳ is the most common type of CPT in children. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

[The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured. Results: After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) (P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) (P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0-15 989) (P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 (P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions: The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

[Poor sleep quality contributes to occurrence of posttraumatic stress disorder in trauma patients].

OBJECTIVE: To evaluate the impact of poor sleep quality on occurrence of post-traumatic stress disorder (PTSD) in trauma patients. METHODS: We prospectively recruited 256 trauma patients hospitalized in 4 general hospitals in Zunyi during the period from October, 2021 to November, 2022, and 226 of the participants completed the PTSD survey and assessment. The patients' sleep quality within a month before trauma was estimated using Pittsburgh Sleep Quality Index (PSQI), and their sleep quality within 7 days after admission was monitored by smart bracelet sleep monitoring; the PTSD Checklist-Civilian Version (PCL-C) was used to detect the occurrence of PTSD during the follow-up. RESULTS: The detection rate of PTSD in the patients was 19.47% at 1 month and 17.61% at 3 months after trauma. The patients who developed PTSD had poorer sleep quality before the trauma, as shown by significantly higher PSQI scale scores (P < 0.001), than those without PTSD, and they showed a sleep abnormality rate as high as 72.73% prior to PTSD onset. Within 7 days after admission, the patients developing PTSD had lower sleep quality scores with more frequent night awakenings (P < 0.05). A 1 month and 3 months after trauma, the patients with PTSD had significantly higher PSQI scores than those without PTSD (P < 0.05). CONCLUSION: PTSD is more likely to occur in trauma patients with poor sleep quality before trauma.

[A Mendelian randomization study on the relationship between insomnia and osteoporosis].

Objective: To explore the relationship between insomnia and osteoporosis. Methods: Mendelian randomization (MR) analysis were used in this study. The single nucleotide polymorphisms (SNPs) related to insomnia from genome-wide association analysis research data were selected as the instrumental variables by using inverse variance weighted (IVW), MR-Egger regression, weighted median method, maximum likelihood, penalized weighted median estimator, and Mendelian randomization robust adjusted profile score (MR-RAPS) to determine the causal relationship between insomnia and osteoporosis. Odds ratio (OR) and 95% confidence interval (CI) values were used to evaluate the association between insomnia and osteoporosis. Cochran's Q-test was used to detect heterogeneity of SNPs, MR-Egger regression was used to test for level pleiotropy, and the leave-one-out method was used to test sensitivity, MR pleiotropy residual sum and outlier (MR-PRESSO) method and radial MR were used to detect erroneous outliers. Results: The screening criteria were set based on the three major assumptions of MR; finally, 31 SNPs were included in the MR analysis. The results of MR causal effect analysis using the IVW method showed that insomnia increased the risk of osteoporosis by about 0.7% (OR=1.007, 95%CI 1.001-1.014, P=0.044); heterogeneity testing showed heterogeneity between SNPs (Q=57.91, P<0.001); and the MR- Egger intercept test did not indicate horizontal pleiotropy in this study (intercept value=3.807×10-5, P=0.888). Leave-one-out method showed that no single SNP had a significant impact on the overall results. No abnormal SNP was detected according to the MR-PRESSO results (P=0.059), and radial MR did not detect any outliers. Conclusion: Mendelian randomization analysis showed that insomnia can increase the risk of osteoporosis.

[Soil microorganisms and physicochemical properties in marshlands along the Yangtze River basin at different types of land use and their effects on distribution of Oncomelania hupensis snails].

OBJECTIVE: To investigating the microbial communities and physicochemical properties of soil and distribution of Oncomelania hupensis snails in marshlands along the Yangtze River basin at different types of land use, and to examine the effects of soil microorganisms and physicochemical properties on snail distribution, so as to provide insights into snail control and schistosomiasis prevention in marshland along the Yangtze River basin. METHODS: Marshlands with four types of land use were selected along the Yangtze River basin on April 2021, including poplar forest-crops integrated planting, reed areas, agricultural cultivation lands and ditches. The distribution of snails and physicochemical properties of soil were investigated in marshlands with different types of land use, and the V3 to V4 regions of the bacterial 16S ribosomal RNA (16S rRNA) gene, fungal internal transcribed spacer-1 (ITS1) gene and algal ribulose-bisphosphate carboxylase (rbcL) gene in soils were subjected to high-throughput sequencing. The occurrence of frames with living snails and density of living snails were compared in marshland with different types of land use. The associations of soil microorganisms and physicochemical properties with the density of living snails were examined using Pearson correlation analysis, and the contributions of soil microorganisms and physicochemical properties to the density of living snails were evaluated using variance partitioning analysis. RESULTS: In marshlands with four types of land use, the greatest occurrence of frames with living snails [(4.94 ± 2.14)%] and density of living snails [(0.070 ± 0.026) snails/0.1 m2] were seen in ditches, and the lowest were found in [(1.23 ± 1.23)%] agricultural cultivation lands [(0.016 ± 0.019) snails/0.1 m2]. A total of 2 phyla, 5 classes, 8 orders, 9 families and 11 genera of algae were detected in soils at four types of land use, with Chlorophyta as the dominant phylum and Pseudoneochloris as the dominant genus. A total of 44 phyla, 134 classes, 281 orders, 338 families and 516 genera of bacteria were detected in soils at four types of land use, with Proteobacteria and Acidobacteriota as the dominant phyla and uncultured Acidobacterium, MND1, Mitrospira, Haliangium and Sphingomonas as dominant genera. A total of 11 phyla, 41 classes, 108 orders, 223 families and 408 genera of fungi were detected in soils at four types of land use, with phyla Ascomycota, Basidiomycota and Mortierellomycota presenting high relative abundances and genera Cladorrhinum, Mortierella and Humicola presenting high relative abundances. Pearson correlation analysis revealed that the density of living snails correlated negatively with the relative abundance of Proteobacteria (r = -0.965, P < 0.05) and soil electronic conductivity (r = -0.962, P < 0.05) and positively with soil moisture (r = 0.951, P < 0.05). Variance partitioning analysis demonstrated that the physicochemical properties and microorganisms of soil contributed 69% and 10% to the density of living snails, respectively. CONCLUSIONS: The diversity of microbial communities varies in soils at different types of land use in marshland along the Yangtze River basin, and the physicochemical properties and microorganisms of soils may affect the distribution of O. hupensis snails.

Chemodiversity of dissolved organic matter exports from subtropical humid catchment driven by hydrological connectivity.

The quantity and quality of dissolved organic matter (DOM) exported from source areas are closely related to hydrological linkage between source areas and streams, that is hydrological connectivity. However, understanding of how hydrological connectivity regulates the export of catchment DOM components remains inadequate. In this study, high-frequency monitoring of groundwater and runoff from subtropical humid catchment was conducted for 20 months, and hydrological connectivity was quantitatively characterized by considering both surface and subsurface hydrological processes. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was utilized to investigate the DOM molecular composition. Results showed that over half of the areas in the catchment could not persistently establish hydrological connectivity with the stream during the rainfall. The average proportion of lignin was the highest in DOM components, followed by tannin and proteins. Additionally, both modified aromaticity index and double bond equivalence reached maximums at peak discharge, reflecting terrestrial materials could increase DOM aromaticity and unsaturated degree. Partial least square-structural equation modeling revealed significantly direct effects of rainfall, antecedent conditions, and hydrological connectivity on dissolved organic carbon (DOC) export. Furthermore, nonlinear relationships were observed between hydrological connectivity and DOC, tannin, and condensed aromatics. Specifically, the instantaneous DOC flux increased dramatically when the hydrological connectivity strength exceeded 0.14; tannin and condensed aromatics exhibited a rapid increase with rising connectivity strength, but remained stable at connectivity strength above 0.25. However, hydrological connectivity showed no significant correlation with unstable components (such as lipids, protein, amino sugars, and carbohydrates). These results provide new insights into hydrological controls on the quantity and quality of DOM export and contribute to developing appropriate catchment management strategies for carbon storage.

[Silent pulmonary shadows].

An elderly woman with a 1-year history of pulmonary shadows was admitted because of intermittent cough and sputum production for 2 months. Chest computed tomography (CT) scans showed bilateral consolidations and ground-glass opacities, with areas of low attenuation inside consolidative opacities on the mediastinal window. Previous history of radiotherapy for nasopharyngeal carcinoma and long-term use of a compound menthol nasal drops provided were important clues to the diagnosis. CT scan-guided needle lung biopsy and bronchoalveolar lavage were performed, and lipid-laden macrophages were confirmed in both bronchoalveolar lavage and lung tissue. Final diagnosis of exogenous lipoid pneumonia was made on the basis of her risk factors for aspiration, history of oil exposure, and classic radiological and histopathological features. Symptoms improved after discontinuation of causative exposure. It is important for clinicians to raise awareness of exogenous lipoid pneumonia and other aspiration lung diseases.

[Fabrication of a coral-like barium titanate nano-piezoelectric coating and its effect on promoting osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro].

Objective: To investigate the biocompatibility of coral-like barium titanate nano-piezoelectric coatings and the influence of ultrasound-excited piezoelectric effect on the early osteogenic differentiation. Methods: The barium titanate nano-piezoelectric coating (the coating group) was prepared on the surface of titanium metal by anodic oxidation, hydrothermal reaction and high-temperature annealing, and polished titanium specimens were used as control group. The surface morphology, composition, and crystal phase and hydrophilicity of the two groups of titanium specimens were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy and contact angle meter. The piezoelectric properties of the materials were characterized by piezoresponse force microscopy. Rat bone marrow mesenchymal stem cells (BMSC) were cultured and identified and seeded the surface of titanium specimens in two groups. The cells seeded on blank culture plates were used as blank group. After low intensity pulsed ultrasound intervention, cell proliferation and live/dead staining were detected to evaluate cytocompatibility of the coatings. Alkaline phosphatase (ALP) activity of each group was detected by ALP staining kit, and the expression of osteogenesis-related genes [integrin, bone morphogenetic protein 2 (BMP-2), Runt-related transcription factor 2 (RUNX2)] was detected by real-time fluorescent quantitative PCR (RT-qPCR) to evaluate the effect of the coating on promoting the early osteogenic differentiation of BMSC. Results: The surface of titanium specimens in the coating group showed a uniform coral-like morphology, and the diameter of the coral tentacles was 70-100 nm. The main component was tetragonal barium titanate. The surface hydrophilicity of the coating group (water contact angle 10.12°± 0.93°) was significantly better than that of the control group (water contact angle 78.32°±0.71°) (F= 10 165.91, P<0.001). The coating has a stable piezoelectric property with a piezoelectric constant of about 5 pC/N. Cell experiments showed that, with or without ultrasound, the cell proliferation activity of the coating group was significantly lower than that of the blank group and the control group on the third day (P<0.05). On the fifth day, with or without ultrasound, there was no significant difference in cell proliferation activity between the three groups (P>0.05). After 7 days of culture, the ALP activity of the coating group was significantly higher than that of the blank group and the control group (P<0.05). The results of RT-qPCR showed that the mRNA expression of integrin and BMP-2 in the coating group with ultrasound was significantly higher than that in the other groups with ultrasound, and was higher than that of the coating group without ultrasound (P<0.05). The expression of integrin mRNA in the control group with ultrasound was significantly higher than that in the control group without ultrasound (P<0.05). The expression of RUNX2 mRNA in the coating group with ultrasound was significantly higher than that in the coating group without ultrasound (P<0.05). Conclusions: The coral-like barium titanate nano-piezoelectric coating exhibits favorable biocompatibility and stable piezoelectric property, and facilitates the early osteogenic differentiation of BMSC under the excitation of low-intensity pulsed ultrasound.

[Clinical characteristics of children with severe SARS-CoV-2 infection in Yunnan].

Objective: To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality. Methods: This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results: The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups (P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×109/L, 479 (298, 594) vs. 268 (124, 424) µg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) µg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases (OR=0.01, 95%CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) (OR=3.31, 95%CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) (OR=1.56, 95%CI 1.05-2.32, P=0.029) and D dimer (OR=1.49, 95%CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95%CI 0.79-0.94), 0.89 (95%CI 0.84-0.95) and 0.87 (95%CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions: Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.

[Current status and prospects of genetic research on membranous nephropathy].

Primary membranous nephropathy (PMN) is one of the most frequent pathological subtypes of nephrotic syndrome in adults. The use of genome-wide association study (GWAS) technology has propelled the transition from conventional medicine to precision medicine, offering a fresh perspective for comprehending the pathogenesis of PMN and individual variations in greater detail. Furthermore, GWAS will aid in clinical translation, laying a firm foundation for the precise diagnosis and treatment of PMN.

[A case of silicosis complicated with non-tuberculous mycobacterium pulmonary disease].

Non-tuberculosis mycobacterium (NTM) refers to a general term for a large group of mycobacteria, excluding the mycobacterium tuberculosis and mycobacterium leprae, which is an opportunistic pathogen. NTM pulmonary disease and pulmonary tuberculosis have very similar clinical and imaging manifestations. Ordinary sputum tests can not distinguish between mycobacterium tuberculosis and NTM accurately, and it needs to be differentiated through detection methods such as mycobacterium culture medium, high-performance liquid chromatography, and molecular biology. During the diagnosis of occupational pneumoconiosis, a sandblasting and polishing worker's lung CT showed dynamic changes in infiltrating shadows and cavities in the right lung. A sputum drug sensitivity test showed NTM infection, but the patient refused treatment. After 20 months, the CT examination of the lung showed further enlargement of infiltrating shadows and cavities, and NTM bacterial identification showed intracellular mycobacterial infection. Amikacin, moxifloxacin, azithromycin, and ethambutol combined antibacterial treatment were given. Currently, the patient is still under treatment.

[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.

Estragole Ameliorates CFA Induced Rheumatoid Arthritis Symptoms in Wistar Rats by Inhibiting JAK-2/STAT-3 Pathway.

The present study was conducted to scrutinize the pharmacological effect of Estragole (ESG) against CFA-induced arthritis in rats. The rats underwent induction of arthritis using the administration of CFA and after that, the rats were randomly divided into five different groups, where three groups correspond to diverse dosages of ESG, and the other two were control and CFA-arthritic control. Results of the study suggested that ESG in a dose-dependent manner, improves body weight and arthritis score of rats as evidenced by reduction of hind-paw volume. ESG also improved the antioxidant status of rats by reducing MDA levels and enhancing the concentration of endogenous antioxidants SOD and GPx. The level of pro-inflammatory cytokines was also found to be reduced in the case of ESG treated group as compared to CFA-group. In a western blot analysis, ESH showed downregulation of p-JAK-2/STAT-3. The study provided concrete evidence for the protective effect of ESG against rheumatoid arthritis in rats.

Epidemiology of healthcare-associated Pseudomonas aeruginosa in intensive care units: are sink drains to blame?

BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of healthcare-associated infection (PA-HAI) in the intensive care unit (ICU). AIM: To describe the epidemiology of PA-HAI in ICUs in Ontario, Canada, and to identify episodes of sink-to-patient PA transmission. METHODS: This was a prospective cohort study of patients in six ICUs from 2018 to 2019, with retrieval of PA clinical isolates, and PA-screening of antimicrobial-resistant organism surveillance rectal swabs, and of sink drain, air, and faucet samples. All PA isolates underwent whole-genome sequencing. PA-HAI was defined using US National Healthcare Safety Network criteria. ICU-acquired PA was defined as PA isolated from specimens obtained ≥48 h after ICU admission in those with prior negative rectal swabs. Sink-to-patient PA transmission was defined as ICU-acquired PA with close genomic relationship to isolate(s) previously recovered from sinks in a room/bedspace occupied 3-14 days prior to collection date of the relevant patient specimen. FINDINGS: Over ten months, 72 PA-HAIs occurred among 60/4263 admissions. The rate of PA-HAI was 2.40 per 1000 patient-ICU-days; higher in patients who were PA-colonized on admission. PA-HAI was associated with longer stay (median: 26 vs 3 days uninfected; P < 0.001) and contributed to death in 22/60 cases (36.7%). Fifty-eight admissions with ICU-acquired PA were identified, contributing 35/72 (48.6%) PA-HAIs. Four patients with five PA-HAIs (6.9%) had closely related isolates previously recovered from their room/bedspace sinks. CONCLUSION: Nearly half of PA causing HAI appeared to be acquired in ICUs, and 7% of PA-HAIs were associated with sink-to-patient transmission. Sinks may be an under-recognized reservoir for HAIs.

Association between trajectories of systolic blood pressure and frailty outcome in middle-aged and older adults.

OBJECTIVES: The association between blood pressure and frailty outcome in the middle-aged and older population remains controversial. This study aimed to examine the relationship between trajectories of systolic blood pressure (SBP) and new-onset frailty. DESIGN: Cohort study with a 7-year follow-up. SETTING AND PARTICIPANTS: Data were derived from 4 waves (2011, 2013, 2015 and 2018) of the China Health and Retirement Longitudinal Study and 6168 participants aged ≥45 years were included in the study. METHODS: The frailty index (FI) was constructed based on 40 scored items, with FI ≥ 0.25 defined as frailty. We identified the 5-year trajectory of SBP by latent class trajectory modeling. The association between SBP trajectories and frailty was explored based on hazard ratios (HR) by four Cox proportional hazards models. Furthermore, we also investigated the relationship between mean SBP and systolic blood pressure variability (SBPV) and frailty. RESULTS: 6168 participants were included in this study with a mean age of 59 years. We identified five trajectories based on SBP, which are maintained low-stable SBP (T0), moderate-stable SBP (T1), remitting then increasing SBP (T2), increasing then remitting SBP (T3), and remaining stable at high SBP levels (T4). During the 7-year follow-up period, frailty outcome occurred in 1415 participants. After adjusting for other confounders, the two trajectories labeled "T2" and "T4" were associated with a higher risk of frailty compared with T0. In addition, elevated SBP and increased SBPV were associated with risk of frailty. CONCLUSIONS: Higher risk of frailty occurred in two trajectories, remitting then increasing and remaining stable at high SBP levels, were associated with a relatively higher risk of frailty.

Subsurface hydrological connectivity controls nitrate export flux in a hilly catchment.

Subsurface runoff represents the main pathway of nitrate transport in hilly catchments. The magnitude of nitrate export from a source area is closely related to subsurface hydrological connectivity, which refers to the linkage of separate regions of a catchment via subsurface runoff. However, understanding of how subsurface hydrological connectivity regulates catchment nitrate export remains insufficient. This study conducted high-frequency monitoring of shallow groundwater in a hilly catchment over 17 months. Subsurface hydrological connectivity of the catchment over 38 rainfall events was analyzed by combining topography-based upscaling of shallow groundwater and graph theory. Moreover, cross-correlation analysis was used to evaluate the time-series similarity between subsurface hydrological connectivity and nitrate flux during rainfall events. The results showed that the maximum subsurface hydrological connectivity during 32 out of 38 rainfall events was below 0.5. Although subsurface flow paths (i.e., the pathways of lateral subsurface runoff) exhibited clear dynamic extension and contraction during rainfall events, most areas in the catchment did not establish subsurface hydrological connectivity with the stream. The primary pattern of nitrate export was flushing (44.7%), followed by dilution (34.2%), and chemostatic behavior (21.1%). A threshold relationship between subsurface hydrological connectivity and nitrate flux was identified, with nitrate flux rapidly increasing after the subsurface connectivity strength exceeded 0.121. Moreover, the median value of cross-correlation coefficients reached 0.67, which indicated subsurface hydrological connectivity exerts a strong control on nitrate flux. However, this control effect is not constant and it increases with rainfall amount and intensity as a power function. The results of this study provide comprehensive insights into the subsurface hydrological control of catchment nitrate export.

In ovo injection of AZD6244 suppresses feather follicle development by the inhibition of ERK and Wnt/ß-catenin pathways in goose embryos (Anser cygnoides).

1. Feathers are an important product from poultry, and the state of feather growth and development plays an important role in their economic value.2. In total, 120 eggs were selected for immunoblotting and immunolocalisation experiments of ERK and ß-catenin proteins in different developmental stages of goose embryos. The ERK protein was highly expressed in the early stage of goose embryo development, while ß-catenin protein was highly expressed in the middle stage of embryo development.3. The 120 eggs were divided into four treatment groups, including an uninjected group (BLANK), a group injected with 100 µl of cosolvent (CK), a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 5 mg/kg AZD6244 containing cosolvent (AZD5) and a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 15 mg/kg AZD6244 containing cosolvent (AZD15). The eggs were injected on the ninth day of embryonic development (E9). Samples were collected at E21.5 to observe feather width, feather follicle diameter, ERK and Wnt/ß-catenin pathway protein expression.4. The AZD5 and AZD15 doses were within the embryonic safety range compared to the BLANK and CK groups and had no significant effect on the survival rate and weight at the inflection point, but significantly reduced the feather width and feather follicle diameter (p < 0.05). The AZD6244 treatment inhibited ERK protein phosphorylation levels and blocked the Wnt/ß-catenin pathway, which in turn significantly down-regulated the expression levels of FZD4, ß-catenin, TCF4 and LEF1 (p < 0.05), with an inhibitory effect in the AZD15 group being more significant. The immunohistochemical results of ß-catenin and p-ERK were consistent with Western blot results.5. The small molecule inhibitor AZD6244 regulated the growth and development of feather follicles in goose embryos by the ERK and Wnt/ß-catenin pathways.

[Diagnostic value of high frequency oscillation in localization of type â ¡ focal cortical dysplasia epilepsy].

Retrospective analysis was conducted on 9 patients with type Ⅱ focal cortical dysplasia (FCD) who underwent stereo-electroencephalography (SEEG) implantation in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University from November 2020 to February 2023. The onset area, onset time, and frequency of high-frequency oscillations (HFO) were analyzed and the correlation of HFOs with interictal, preictal, and ictal periods. SEEG recordings of 80-500 Hz HFOs were observed in both interictal and ictal periods in 9 patients, with 6 patients exhibiting fast ripples (FR) in the range of 250-500 Hz. Surgical resection of the seizure onset area and FR-generating electrodes was performed, and postoperative follow-up for over 2 years indicated Engel I in 5 cases. 6 patients showed continuous discharge during the preictal period, and the distribution index of continuous discharge was positively correlated with seizure frequency. HFOs in the range of 80-500 Hz were present in all four seizure onset patterns during the ictal period. The onset area and FR-emitting electrode were surgically removed in 6 patients with continuous discharge and overlapping HFOs during the preictal period, with 5 cases of Engel I. Type Ⅱ FCD discharges exhibited complexity, high discharge indices, and a close association with HFOs. Compared with the spike wave, the electrode range of HF is more limited, and the incidence of HF before attack is significantly increased, which is closely correlated with the onset area. The simultaneous occurrence of HFO and the spike waves has higher diagnostic value than the individual occurrence, effectively enhancing surgical efficacy.

[Clinical and genetic analysis of a patient with HUPRA syndrome due to missense variants of SARS2 gene and literature review].

Objective: To explore the clinical manifestations and genotype of an infant with hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis syndrome (HUPRAS). Methods: Clinical data of the patient were collected. Peripheral blood samples from the patient and his parents were acquainted for whole exome sequencing. The filtrated variants were verified by Sanger sequencing. The pathogenicity of the variants was predicted by bioinformatic tools. Results: The patient is a male infant of 6 months old, carrying two missense variants in the SARS2 allele: a paternal inherited c.1205G>A (p. Arg402His) and a maternal inherited c.680G>A (p. Arg227Gln). The two variants were in extremely low population frequencies. The pathogenetic prediction tools categorized them as deleterious. Arg402 and Arg227 were highly conserved in evolution. The variants led to changes in the hydrogen bonds and hydrophobicity of seryl-tRNA synthetase encoded by SARS2. Conclusions: c.1205G>A (p. Arg402His) and c.680G>A (p. Arg227Gln) are the possible causative variants of the HUPRA syndrome.