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General paresis is a rare type of syphilis characterized by progressive cognitive impairment and psychiatric syndromes. It is often misdiagnosed because of its rarity and similarity with other diseases. We aimed to comprehensively investigate the clinical, radiological, pathological, and prognostic features of general paresis, and compare it with other dementias. Between August 2019 and January 2024, patients were recruited from a Memory Clinic Setting of National Center for Neurological Disorders in China. Participants underwent clinical evaluation, laboratory testing, and imaging, and were followed after treatment. Comparative analysis was conducted on clinical features and neuropsychiatric assessments, while brain image features were investigated using linear regression models and SuStaIn models. Seventy-eight patients were included, with 90% being male. The median duration from symptom onset to the first diagnostic visit was 15 months. Sixty-three patients were followed for an average of 1.4 years. Cognitive impairment emerged as the most common symptom, with half of the patients co-existed with motor symptoms. Impairment across all cognitive domains accompanied by positive psychiatric symptoms raised suspicion for general paresis, and distinguishing it from Alzheimer's disease, frontotemporal dementia, and anti-LGI1 encephalitis-related dementia. Common imaging abnormalities in general paresis included whole brain atrophy and cortical hypointensity. The hippocampal-predominant and hippocampal-sparing atrophy subtypes were identified. Autoimmune responses in general paresis were demonstrated through the detection of autoimmune encephalitis antibodies in 11% of patients. Pathological amyloid changes were observed in 26% of patients, while elevated total tau levels were found in 30%. Seventy percent of patients showed improvement following treatment, with a reduction in the number of symptoms observed across all cases. This study identifies specific clinical syndromes and radiological features of general paresis and refines the understanding of its prognosis. We provide clues to distinguish general paresis from other dementias, facilitating early diagnosis and treatment. The role of novel pathological changes in general paresis needs to be further studied., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Exposure to chemical pollutants and their effects on the gut microbiome during early life are scarce, especially the effects of mixed exposures. Plasma pollutants levels were measured using gas chromatography -triple quadrupole mass spectrometer (GC-MS/MS) among 304 infants in the neonatal ward at Hunan Children's hospital, China, and gut microbiota was derived from 16S rRNA sequencing. We assessed exposure and alpha diversity using generalized linear models, and variation in beta diversity (Bray-Curtis), taxa abundance (MaAsLin2), and employed Bayesian kernel machine regression (BKMR) to investigate the association of pollutants mixture with alpha diversity and taxa. PBDE-99 was positively associated with the Chao1 index (β = 4.29, 95%CI:1.54,7.03). Exposure to the pesticides trifluralin, γ-BHC, and methidathion significantly affected beta diversity (all P FDR < 0.05). PBDE-100, β-BHC, phosalone, methiamitron, fenpropathrin, δ-BHC, and o,p'-DDT were associated with changes in taxa abundance, including negative associations [e.g., Staphylococcus, Bacteroides, Bifidobacterium, and Corynebacterium] and positive associations [e.g., Acinetobacter and Pseudomonas]. An interaction between o,p'-DDT and δ-BHC on Pseudomonas was also found in BKMR models. Our findings suggest that chemical pollutants are associated with gut microbiome changes in hospitalized infants, providing new insights into the mechanisms of chemical pollutants toxicity. Further validation is necessary to confirm these associations and explore their long-term health effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: The triangular fibrocartilage complex (TFCC) plays an important role in distal radioulnar joint (DRUJ) stabilization, and is frequently torn. In particular, when conservative treatment fails, surgical treatment is needed., Methods: In this retrospective study, fourteen individuals with TFCC foveal tears and DRUJ instability were admitted to the department and treated with arthroscopic-assisted modified "double loop suture" transosseous repair between January 2021 and 2023. During surgery, an osseous tunnel was established, and two nickel-based alloy loops and a 2-0 polydioxanone II (PDS II) suture were used to achieve anatomic repair of the tear. All patients received supervised rehabilitation exercises after surgery., Results: The patients were followed for an average of 15 months. The mean visual analog scale (VAS) score, which was used to assess the pain intensity experienced by patients using their affected hand, significantly decreased from 5 (95% CI 4-6) points preoperatively to 2 (95% CI 1-3) points at the final follow-up (p < 0.05). The grip strength and Disabilities of the Arm, Shoulder, and Hand (DASH) score before surgery were 17 (95% CI 13-22) kg and 35 (95% CI 26-44) points, respectively, compared with 21 (95% CI 16-25) kg and 16 (95% CI 9-22) points at the final follow-up (p < 0.05). The median Patient-Rated Wrist Evaluation (PRWE) score was 28 (IQR 21, 48) before surgery, which then significantly decreased to 10 (IQR 6, 15) at the final follow-up. The mean flexion‒extension range of the wrist significantly increased from 111 (95% CI 100-122) degrees before surgery to 116 (95% CI 106-126) degrees postsurgery (p < 0.05), and the mean pronation‒supination range of the forearm significantly improved from 125 (95% CI 110-140) degrees to 135 (95% CI 121-149) degrees at the final follow-up assessment (p < 0.05). None of the assessed individuals exhibited DRUJ instability, as evaluated by the ballottement test or developed surgery-related complications such as postoperative infection, injury to the dorsal branch of the ulnar nerve or iatrogenic ulnar styloid fracture caused by the establishment of an osseous tunnel., Conclusion: Arthroscopic-assisted modified "double loop suture" is a secure and efficient approach for achieving anatomic repair of TFCC foveal tears, with satisfactory functional improvement and DRUJ stability restoration., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures performed in research involving human participants are in accordance with the ethical standards of the institutional and/or National Research Councils and the 1964 Declaration of Helsinki and its later amendments or similar ethical standards. This study was provided by the Ethical Committee (Department of Medical Affairs) of Norinco Gerenal Hospital, Xi′an, China on 30 November 2021.Ethics Review number: 2021xm007. Confirm that informed consent has been obtained from all subjects and/or their legal guardians. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and accompanying images. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: Early diagnosis of intensive care unit-acquired weakness (ICUAW) is crucial for improving the outcomes of critically ill patients. Hence, this study was designed to identify predisposing factors for ICUAW and establish a predictive model for the early diagnosis of ICUAW., Methods: This prospective observational multicenter study included septic patients from the comprehensive ICUs of West China Hospital of Sichuan University and 10 other hospitals between September and November 2023. Inclusion criteria were as follows: age over 18 years; expected ICU stay longer than 3 days; and voluntary informed consent. Patients were classified into ICUAW (MRC score < 48) and non-ICUAW (MRC score ≥ 48) groups based on muscle strength assessments. The analyzed key predictive factors encompassed demographic data, SOFA and APACHE II scores, inflammatory markers (PCT, IL-6, and CRP), and ultrasound measurements of muscle thickness and cross-sectional area. Logistic regression analysis was conducted for variable selection and nomogram model construction., Results: A total of 116 septic patients were included, comprising 77 males and 39 females (mean age: 56.94 ± 19.90 years). A nomogram model predicting ICUAW probability was developed, which involved vastus intermedius diameter, rectus femoris cross-sectional area, IL-6, and CRP. The AUC of the composite diagnostic ROC curve was 0.966 (95%CI: 0.936 - 0.996), with a sensitivity of 88% and a specificity of 95.8%., Conclusions: Conclusively, a nomogram model is constructed for diagnosing ICUAW in septic patients, which is simple and rapid and allows for visual representation, with excellent diagnostic capability., Competing Interests: Declarations. Ethics approval and consent to participate: The research protocol received approval from the Biomedical Ethics Review Committee of West China Hospital of Sichuan University (Approval Number 2023 − 1422). Written informed consent was obtained from all patients. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

To evaluate the effect of bronchoalveolar lavage (BAL) on the clinical prognosis of children with macrolide drug-resistant Mycoplasma pneumoniae pneumonia (MRMPP) in a retrospective cohort study based on propensity score matching (PSM).A retrospective cohort study based on propensity score matching retrospectively collected the clinical data of hospitalized patients diagnosed with mycoplasma macrolide drug-resistant pneumonia (MRMPP) in Respiratory Department of Hunan Children's Hospital from January 2020 to August 2023. According to whether bronchoalveolar lavage (BAL) was performed during hospitalization, the children were divided into BAL group and non-BAL group, and the baseline information of the two groups was matched by propensity scores, and the clinical prognosis was compared. A total of 302 children were screened, and 150 cases were successfully matched, including 59 cases in the BAL group and 91 cases in the non-BAL group. The results showed that the differences between the non-BAL group and the BAL group before PSM( P <0.05) were significantly different in age [(4.60±2.97)years vs (5.41±3.02) years, t =-2.273, P =0.024], shortness of breath (9.4% vs 22.5%, χ 2 =9.864, P =0.002), and radiographic manifestations [lung interstitial changes (29.8% vs 15.3%, χ 2 =8.009, P =0.005), lung consolidation (17.3% vs 55.9%, χ 2 =48.457, P <0.001), spotted flaky infiltrates (52.4% vs 27.9%, χ 2 =17.056, P <0.001)], bacterial infection (3.2% vs 9.2%, χ 2 =4.845, P =0.028), duration of azithromycin or doxycycline use [4(2, 5) days vs 5(3, 6) days, Z =-2.374, P =0.018], White Blood Cell Count at admission [7.94 (6.25, 10.34)×10 9 /L vs 7.21 (5.65, 9.01)×10 9 /L, Z =-2.445, P =0.014], D Dimer [0.58 (0.44, 0.83) μg/ml vs 0.80 (0.52, 1.12) μg/ml, Z =-3.154, P =0.002], but there was no significant difference between the two groups in the above indexes after PSM ( P >0.05). The duration of hospitalization, cough relief, disappearance of rales and fever in the BAL group was shortened in the BAL group compared with that in the non-BAL group [5 (4, 7) days vs 7 (5, 8) days, Z =-2.373, P =0.018], and the difference was statistically significant ( P <0.05). Linear regression analysis of PSM cohort study showed that BAL was negatively correlated with fever time (β=-4.369, 95% CI :-8.600--0.138, P <0.05). In conclusion, BAL can shorten the fever time of MRMPP, and early BAL in addition to conventional treatment has a positive effect on the prognosis of children.

The gut microbiota is closely related to infant health. However, the impact of environmental factors on the gut microbiota has not been widely investigated, particularly in vulnerable populations such as infants admitted to the neonatal intensive care unit (NICU). This study investigated the association between exposure to 12 metals and the composition of the gut microbiota in infants admitted to the NICU. Metal concentrations were determined in serum samples obtained from 107 infants admitted to the NICU at Hunan Children's hospital, China. Gut microbiota data were derived from 16S rRNA sequencing using stool samples. Generalized linear regression (GLR) models and Bayesian kernel machine regression (BKMR) analyses were used to estimate the associations between metals and both alpha-diversity indices and bacterial taxa. The GLR models showed that tin correlated negatively with the Shannon index (β = -0.55, 95% conficence interval [CI]: -0.79, -0.30, P FDR < 0.001) and positively with the Simpson index (β = 0.26, 95% CI: 0.13, 0.39, P FDR < 0.001). The BKMR analysis yielded similar results, showing that tin had the largest posterior inclusion probability for both the Shannon (0.986) and the Simpson (0.796) indices. Tin, cadmium, mercury, lead, and thallium were associated with changes in one or more taxa at the genus level. The BKMR analysis also revealed a negative correlation between metal mixtures and Clostridium&#95;sensu&#95;stricto, and tin contibuted mostly to the negative correlation. Early postnatal exposure to metals were associated with differences in the microbiome among infants admitted to the NICU. However, as the study was cross-sectional, these relationships must be confirmed in further studies., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background Neoadjuvant chemotherapy (NCT) is gaining acceptance for the management of locally advanced rectal cancer (LARC) in patients without negative prognostic factors. However, the value of MRI in evaluating tumor response after NCT remains unclear. Purpose To investigate the accuracy of MRI in assessing pathologic complete response in participants with LARC who underwent surgery after NCT without radiation. Materials and Methods A retrospective imaging substudy was conducted within two consecutive prospective clinical trials: the expanded phase II trial (from December 2017 to May 2021) and the COPEC trial (comparison of tumor response to two or four cycles of neoadjuvant chemotherapy alone, ongoing from August 2021). All included participants received four cycles of capecitabine combined with oxaliplatin (or CAPOX) before surgery. Three radiologists who were blinded to the clinicopathologic data independently evaluated the tumor response using five methods, namely, MR tumor regression grade (MR-TRG) alone, diffusion-weighted imaging (DWI) alone, DWI-modified MR-TRG (DWImodMR-TRG), MRI complete response, and radiologic neoadjuvant response score. With pathologic assessment serving as the reference standard, the positive and negative predictive values, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined to evaluate the accuracy and performance of these models. The AUCs of the models were compared using the DeLong test. Results A total of 224 participants were included, comprising 119 from the expanded phase II trial (median age, 61 years [IQR, 53-67]; 89 male) and 105 from the COPEC trial (median age, 59 years [IQR, 53-67]; 65 male). MR-TRG, DWI, DWImodMR-TRG, MRI complete response, and the radiologic neoadjuvant response score were associated with pathologic complete response. DWImodMR-TRG achieved the highest AUC of 0.90 (95% CI: 0.85, 0.95), with a specificity of 89% (162 of 182) and a negative predictive value of 93% (162 of 174). Conclusion MRI-based models were accurate for determining pathologic complete response in participants with LARC following NCT. DWI improved the predictive performance of MRI-based assessment. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Santiago and Shur in this issue.

Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic-parasympathetic activity. The strongest signal in the primary GWAS, the ADAMTS8 locus, was replicated in three independent datasets (N = 1,685-4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association for ADAMTS8, and Mendelian randomization showed lower ADAMTS8 expression with larger hypothalamic volumes. The current study advances our understanding of complex structure-function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The aim was to investigate the association between mixed exposure to phthalates and serum thyroid function among US adolescents. The study used 2007-2008 survey data from the National Health and Nutrition Examination Survey (NHANES). Data on urinary phthalates metabolites and serum thyroid function indicators were collected. The weighted multivariable linear regression models and Bayesian kernel machine regression (BKMR) analyses were used to analyze the relationship between phthalates metabolites and thyroid function. A total of 356 adolescents aged 12-19 years were included in the analysis. Linear regression models showed that mono-(carboxyisoctyl) phthalate (MCOP) was positively correlated with total triiodothyronine (TT3) (β = 0.045, 95% confidence interval [CI] 0.022, 0.068) and thyroid stimulating hormone (TSH) (β = 0.1461, 95% CI 0.059, 0.232), while mono-(carboxyisononyl) phthalate (MCNP) was negatively correlated with TSH (β = - 0.119, 95% CI - 0.196, - 0.042). BKMR analyses showed phthalate metabolites mixtures have significantly positive overall effect on TT3. Exposure to phthalate mixtures might be positively correlated with increased TT3 serum level in US adolescents. The study provided evidence for the association between mixed phthalates exposure and thyroid health in adolescent population., (© 2023. The Author(s).)

Background: A unified clinical definition of feeding intolerance (FI) is urged for better management of enteral nutrition (EN) in critically ill patients. We aimed to identify optimum clinical FI definitions based on reported evidence., Methods: We searched clinical studies comparing FI with non-FI with a clear definition, summarized the evidence by random-effect meta-analyses, and rated the certainty of evidence by the Grading of Recommendations Assessment, Development and Evaluation frameworks., Results: Five thousand five hundred twenty-five records were identified, of which 26 eligible studies enrolled 25,189 adult patients. Most patient-centered outcomes were associated with FI overall. Low to very low certainty evidence established FI defined as large gastric residual volume (GRV) ≥ 250 ± 50 mL combined with any other gastrointestinal symptoms (GIS) had a significant association with high mortalities in particular all-cause hospital mortality (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.40-2.57), the incidence of pneumonia (OR 1.54, 95% CI 1.13-2.09) and prolonged length of hospital stay (mean difference 4.20, 95% CI 2.08-6.32), with a moderate hospital prevalence (41.49%, 95% CI 31.61-51.38%). 3-day enteral feeding (EF) delivered percentage < 80% had a moderate hospital prevalence (38.23%, 95% CI 24.88-51.58) but a marginally significant association with all-cause hospital mortality (OR 1.90, 95% CI 1.03-3.50)., Conclusions: In critically ill adult patients receiving EN, the large-GRV-centered GIS to define FI seemed to be superior to 3-day EF-insufficiency in terms of both close associations with all-cause hospital mortality and acceptable hospital prevalence (Registered PROSPERO: CRD42022326273)., Trial Registration: The protocol for this review and meta-analysis was registered with PROSPERO: CRD42022326273. Registered 10 May 2022., (© 2023. The Author(s).)

Background: The correlations between genetic risk for Alzheimer's disease (AD) with comprehensive brain regions at a regional scale are still not well understood. We aim to explore whether these associations vary across different age stages., Methods: This study used large existing genome-wide association datasets to calculate polygenic risk score (PRS) for AD in two populations from the UK Biobank (N ~ 23 000) and Adolescent Brain Cognitive Development Study (N ~ 4660) who had multimodal macrostructural and microstructural magnetic resonance imaging (MRI) metrics. We used linear mixed-effect models to assess the strength of the association between AD PRS and multiple MRI metrics of regional brain structures at different stages of life., Results: Compared to those with lower PRSs, adolescents with higher PRSs had thinner cortex in the caudal anterior cingulate and supramarginal. In the middle-aged and elderly population, AD PRS had correlations with regional structure shrink primarily located in the cingulate, prefrontal cortex, hippocampus, thalamus, amygdala, and striatum, whereas the brain expansion was concentrated near the occipital lobe. Furthermore, both adults and adolescents with higher PRSs exhibited widespread white matter microstructural changes, indicated by decreased fractional anisotropy (FA) or increased mean diffusivity (MD)., Conclusions: In conclusion, our results suggest genetic loading for AD may influence brain structures in a highly dynamic manner, with dramatically different patterns at different ages. This age-specific change is consistent with the classical pattern of brain impairment observed in AD patients., (© 2023. The Author(s).)

Phthalates are widely used as plasticizer or fragrance ingredients in various consumer products worldwide. However, evidence for the overall effects of mixed exposure to phthalate on kidney function has not been widely investigated. The purpose of this article was to assess the association of urine phthalate metabolite levels and kidney injury parameters in adolescents. We used data from the combined 2007-2016 National Health and Nutrition Examination Survey (NHANES). We fitted weighted linear regressions and Bayesian kernel machine regressions (BKMR) models to explore the association of urinary phthalate metabolites with four parameters of kidney function after adjusting for covariates. Weighted linear regression models showed that MiBP (β = 8.057; P FDR = 0.016) was significantly positively associated with eGFR and MEP (β = -0.799; P FDR < 0.001) was significantly negatively correlated with BUN. BKMR analysis showed that the higher the concentration of phthalate metabolite mixture, the higher eGFR in adolescents. Based on the results of these two models, our findings revealed that mixed exposure to phthalates was associated with elevated eGFR in adolescents. However, as the study is cross-sectional, reverse causality is possible, and altered kidney function may impact the concentration of phthalate metabolites in urine., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To accelerate the onset of systemic lupus erythematosus in C57BL/6 mice by injecting cadmium chloride nanoemulsion and shorten the traditional modeling time., Methods: Pristane cadmium chloride nanoemulsion was prepared, and 66 C57BL/6 mice were randomly divided into four groups. The pristane group was intraperitoneally injected with 0.6 mL of pristane blank nanoemulsion, the model group was injected with 0.6 mL of pristane cadmium chloride nanoemulsion, the Cadmium chloride control group was injected with 0.6 mL of cadmium chloride nanoemulsion, and the control group was injected with the same amount of 0.9% sodium chloride solution. Urine protein content, anti-dsDNA antibody content, Th1 cell/Th2 cell ratio, and kidney staining were detected in each group., Results: The model group began to develop disease in the 4th week, the anti-dsDNA antibody level reached 566.71 ± 1.44 ng/L, and the proteinuria reached 245.38 ± 30.54 ng/mL. The model group showed an onset at least 5 weeks earlier than that in the pristane group. There was no significant difference in anti-dsDNA antibody content between Cadmium chloride control group and blank group. At the 12th week, the Th1/Th2 cell ratio in the model group significantly decreased, and the pathological changes in the kidneys were consistent with the typical manifestations of lupus in mouse models., Conclusion: These results suggest that cadmium chloride promotes earlier onset of pristane-induced systemic lupus erythematosus in a C57BL/6 mouse model.

Background: The cerebellum is recognized as being involved in neurocognitive and motor functions with communication with extra-cerebellar regions relying on the white matter integrity of the cerebellar peduncles. However, the genetic determinants of cerebellar white matter integrity remain largely unknown., Methods: We conducted a genome-wide association analysis of cerebellar white matter microstructure using diffusion tensor imaging data from 25,415 individuals from UK Biobank. The integrity of cerebellar white matter microstructure was measured as fractional anisotropy (FA) and mean diffusivity (MD). Identification of independent genomic loci, functional annotation, and tissue and cell-type analysis were conducted with FUMA. The linkage disequilibrium score regression (LDSC) was used to calculate genetic correlations between cerebellar white matter microstructure and regional brain volumes and brain-related traits. Furthermore, the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework was employed to identify the shared genetic basis between cerebellar white matter microstructure and common brain disorders., Results: We identified 11 genetic loci (P < 8.3 × 10 -9 ) and 86 genes associated with cerebellar white matter microstructure. Further functional enrichment analysis implicated the involvement of GABAergic neurons and cholinergic pathways. Significant polygenetic overlap between cerebellar white matter tracts and their anatomically connected or adjacent brain regions was detected. In addition, we report the overall genetic correlation and specific loci shared between cerebellar white matter microstructural integrity and brain-related traits, including movement, cognitive, psychiatric, and cerebrovascular categories., Conclusions: Collectively, this study represents a step forward in understanding the genetics of cerebellar white matter microstructure and its shared genetic etiology with common brain disorders., Competing Interests: Declaration of Competing Interest Authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: The aims of this study were to evaluate the levels of preretinal oxygen tension in patients with diabetes who did not have hypertension by using three-dimensional spoiled gradient-recalled (3D-SPGR) echo sequence imaging and to explore the correlation between diabetic retinopathy (DR) and changes in preretinal oxygen tension., Method: This study involved 15 patients with type 2 diabetes without hypertension, who were divided into a diabetic retinopathy (DR) group (n = 10 eyes) and a diabetic non-retinopathy (NDR) group (n = 20 eyes), according to the results of a fundus photography test. Another healthy control group (n = 14 eyes) also participated in the study. The preretinal vitreous optic disc area, nasal side, and temporal side signal intensity of the eyes was assessed before and after oxygen inhalation with the use of 3D-SPGR echo magnetic resonance imaging (MRI). The signal acquisition time was 10, 20, 30, 40, and 50 min after oxygen inhalation., Results: The results showed that, in the DR and NDR groups, the preretinal vitreous oxygen tension increased rapidly at 10 min after oxygen inhalation and peaked at 30-40 min, and the increased slope of the DR group was higher than that of the NDR group. The oxygen tension of the preretinal vitreous gradually increased after oxygen inhalation, and the difference between the DR and NDR groups and the control group was statistically significant (P < 0.05). The preretinal vitreous oxygen tension was higher in the optic disc, temporal side, and nasal side in the NDR group than in the control group, and the difference was statistically significant (P < 0.05). The maximum slope ratios of the optic disc and the temporal side of the DR group were greater than those of the control group, and the difference was statistically significant (P < 0.05)., Conclusion: Three-dimensional-SPGR echo MRI sequencing technology is useful for detecting preretinal oxygen tension levels in patients with diabetes. It can be used as one of the functional and imaging observation indicators for the early diagnosis of DR., (© 2022. The Author(s).)

Objective: Oxaliplatin-induced neuropathy is a significant complication of cancer therapy. We aimed at investigating the risk factors of oxaliplatin-induced neuropathy (OIPN) and providing evidence to enhance its prevention., Materials and Methods: PubMed, Medline, Web of Science, Embase, China Knowledge Resource Integrated Database, and the Wanfang Database were searched comprehensively for observational studies investigating the prevalence and risk factors of OIPN from inception to November 30, 2021. The Newcastle-Ottawa Scale was used by two independent reviewers to assess methodological quality. When applicable, we used meta-analysis to determine mean differences and odds ratios for continuous and nominal scaled data., Results: We included 20 studies involving 10,900 participants for analysis. Factors associated with OIPN risk identified by meta-analysis were age, gender, diabetes, anemia, hypomagnesaemia, alcohol consumption, body mass index, body surface area, cumulative oxaliplatin dose and the number of chemotherapy cycles. Factors not associated with OIPN risk included smoking history and chemotherapy regimen., Conclusions: This meta-analysis identified multiple variables associated with OIPN. The recognition of modifiable risk factors is an urgent priority to improve prevention and treatment outcomes.

Brown adipose tissue (BAT) plays a key role in thermogenesis during acute cold exposure. However, it remains unclear how BAT is prepared to rapidly turn on thermogenic genes. Here, we show that damage-specific DNA binding protein 1 (DDB1) mediates the rapid transcription of thermogenic genes upon acute cold exposure. Adipose- or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes. These mice develop hypothermia when subjected to acute cold exposure at 4 °C and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation. Mechanistically, DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b (P-TEFb) to release promoter-proximally paused RNA polymerase II (Pol II), thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure. Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge., Competing Interests: Tong-Jin Zhao holds the position of Editorial Board Member for Life Metabolism, and is blinded from reviewing or making decisions for the manuscript., (© The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.)

Sexual violence and physical fighting are independent risk factors for suicidal behaviors among adolescents. However, whether the concurrence of these two risk factors increases the risk of suicidal behaviors among ideators, and by how much that risk increases are unknown. This study analyzed data from the 2019 National Youth Risk Behavior Surveys. Students who reported having seriously considered attempting suicide in the past year were included (n = 1755). The associations between physical fighting/sexual violence status and the risk of suicide attempt/plan/attempt requiring medical intervention were estimated. The concurrence of physical fighting and sexual violence substantially increased the relative risk of attempted suicide (adjusted relative risk, adRR = 1.99, 95% CI 1.72, 2.29) and attempted suicide requiring medical intervention (adRR = 4.07, 95% CI 2.84, 5.85; subgroup analyses: among women, adRR = 3.33, 95% CI 2.14, 5.17; among men, adRR = 6.25, 95% CI 3.32, 12.28). Among students who had experienced concurrent physical fighting and sexual violence, more suicide-attempt-associated health-risk behaviors were reported by men (median = 14) than women (median = 12) (p = 0.0023). The concurrence of physical fighting and sexual violence among adolescent suicide ideators was shown to be significantly associated with an increased risk of attempted suicide. A wide variety of health-risk behaviors were shown to cluster with the concurrence of physical fighting and sexual violence. This was especially the case among men, consistent with their higher rate of attempted suicide requiring medical intervention., (© 2022. The Author(s).)

Introduction: To analyze the risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock, we had done the retrospective cross-sectional study, which would facilitate the early identification of high-risk patients., Materials and Methods: Datas were retrospectively reviewed from 160 patients, suffering from obstructive urosepsis associated with urolith between December 2013 and December 2019. There were 49 patients complicating by severe sepsis (severe sepsis group), 12 patients complicating by septic shock (septic shock group), and 99 patients without progressing to severe sepsis or septic shock (sepsis group). The data covered age, gender, BMI (body mass index), time interval from ED (emergency department) to admission, WBC count (white blood cell count), NLR (neutrophil/lymphocyte ratio), HGB (hemoglobin), etc. Datas were analyzed by univariate analyses and multivariate logistic regression analysis. The corresponding nomogram prediction model was drawn according to the regression coefficients., Results: Univariate analysis showed that the differences of age, the time interval from ED to admission, history of diabetes mellitus, history of CKI (chronic kidney disease), NLR, HGB, platelet count, TBil (total bilirubin), SCr (serum creatinine), ALB (albumin), PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio), PCT (procalcitonin), and positive rate of pathogens in blood culture were statistically significant (P < 0.05). Multivariatelogistic regression analysis showed that age, SCr, and history of CKI were independent risk factors for progression to severe sepsis, or septic shock (P < 0.05)., Conclusions: Aged ≥ 65 years, SCr ≥ 248 mol/L, and history of CKI were independent risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock. We need to pay more attention to these aspects, when coming across the patients with urolithic sepsis., (© 2022. The Author(s).)

Background: Immunoglobulin (Ig) G4-related disease (IgG4-RD) is an autoimmune disease associated with chronic and progressive inflammation and fibrosis. It is difficult to differentiate IgG4-RD involving the kidney from infectious diseases and malignancy on imaging., Case Summary: We report the case of a 51-year-old Chinese man whose abdominal computed tomography scan showed diffuse bilateral enlargement of the kidneys and perirenal fat, thickening of the renal pelvic walls, and hydronephrosis of the right kidney. Relevant laboratory test results showed a serum creatinine level of 464 μmol/L. The patient was diagnosed with acute renal failure and was started on intermittent hemodialysis. Further tests revealed high serum IgG4 levels (20.8 g/L) and an enlarged right submaxillary lymph node. Biopsy and histopathological examination of the enlarged node led to the diagnosis of IgG4-RD. After corticosteroid therapy, his serum creatinine level quickly decreased to near normal levels., Conclusion: IgG4-RD affecting the renal pelvis or perirenal fat is rare, with atypical imaging features. Multidisciplinary consultation is critical for accurate diagnosis and treatment of this disease. Suspected cases should undergo biopsy to avoid misdiagnosis., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Phosphate disturbances are relatively common in hospitalized patients, especially in critically ill patients. The abnormal phosphate levels may indicate an abnormal body condition. However, little is known about the association between elevated serum phosphate and outcome in critically ill elderly patients. Therefore, the purpose of the present study was to investigate the association between early elevated phosphate and mortality in critically ill elderly patients., Methods: The present study was a retrospective cohort study based on the medical information mart for intensive care IV (MIMIC-IV) database. Patients with age ≥60 years old were enrolled in the present study. The primary outcome in the present study was ICU mortality. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the association between early elevated phosphate and ICU mortality in critically ill elderly patients., Results: Twenty-four thousand two hundred eighty-nine patients were involved in this analysis and 2,417 patients died in ICU. The median age of involved patients was 78.4 (67.5, 82.9) years old. The median level of serum phosphate in the survivor group was 3.6 (3.0, 4.3) mg/dL, and the median level of serum phosphate in the non-survivor group was 4.4 (3.4, 5.8) mg/dL. The level of serum phosphate in the non-survivor group was significantly higher than the survivor group (4.4 vs. 3.6, P<0.001). The multivariate Cox proportional hazard regression demonstrated that elevated phosphate was an independent risk factor for ICU mortality, after adjustment for other covariates (HR=1.056, 95%CI: 1.028-1.085, P<0.001)., Conclusions: In critically ill elderly patients, early elevated phosphate was significantly associated with increased ICU mortality., (© 2022. The Author(s).)

Objective: To investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and the pathological classification of idiopathic orbital inflammatory pseudotumors (IOIPs)., Methods: Nineteen patients who were diagnosed with IOIPs (a total of 24 affected eyes) between November 2018 and December 2020 were included in the study. All the patients underwent magnetic resonance imaging orbital plain scans and IVIM-DWI multiparameter scans before an operation. The true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were obtained. Based on histopathology, the lesions were divided into three types: lymphocytic infiltration, fibrosclerotic, and mixed. The correlation between IVIM-DWI parameters and pathological classification was tested with the histopathological results as the gold standard. The data were analyzed using SPSS version 17.0, with P < 0.05 defined as significant., Results: Among the 19 patients (24 eyes) affected by IOIP, there were no significant differences between IOIP pathological classification and gender or age (P > 0.05). There were statistically significant differences between the D and f values for different pathological types of IOIP and IVIM parameters (P < 0.05), and there was no significant difference in D* value between the different pathological types (P > 0.05)., Conclusion: The D and f values showed correlation with different types of IOIP, and the sensitivity of the D value was higher than that of the f value. The D* value showed no significant distinction between pathological types of IOIP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pu, Liang, He, Shao, Zhou, Xiang, Li, Li and Ji.)

Coral-derived microorganisms have been historically proven to be prolific sources of bioactive secondary metabolites. Twelve benzopyranone and/or xanthone derivatives, including a new benzopyranone with an uncommon carboxyl group at C-8, coniochaetone K ( 1 ), were obtained from the Beibu Gulf-derived coral symbiotic fungus Cladosporium halotolerans GXIMD 02502. Their structures were determined by extensive spectroscopic data interpretation and comparison with literature values. The absolute configuration of 1 was accomplished by comparison of specific optical rotation as well as quantum chemical ECD calculations. The in vitro cytotoxicity of compounds 1 - 12 against two human prostatic cancer cell lines, C4-2B and 22RV1, were evaluated. And compounds 1 , 3 , 6 - 8 , and 10 - 11 demonstrated significant cytotoxicity with inhibitions ranging from 55.8% to 82.1% at the concentration of 10  μ M.

Background: Evidence of glucocorticoids on viral clearance delay of COVID-19 patients is not clear., Methods: In this systematic review and meta-analysis, we searched for studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, and ClinicalTrials.gov from 2019 to April 20, 2021. We mainly pooled the risk ratios (RRs) and mean difference (MD) for viral clearance delay and did subgroup analyses by the severity of illness and doses of glucocorticoids., Results: 38 studies with a total of 9572 patients were identified. Glucocorticoids treatment was associated with delayed viral clearance in COVID-19 patients (adjusted RR 1.52, 95% CI 1.29 to 1.80, I 2  = 52%), based on moderate-quality evidence. In subgroup analyses, risk of viral clearance delay was significant both for COVID-19 patients being mild or moderate ill (adjusted RR 1.86, 95% CI 1.35 to 2.57, I 2  = 48%), and for patients of being severe or critical ill (adjusted RR 1.59, 95% CI 1.23 to 2.07, I 2  = 0%); however, this risk significantly increased for patients taking high doses (unadjusted RR 1.85, 95% CI 1.08 to 3.18; MD 7.19, 95% CI 2.78 to 11.61) or medium doses (adjusted RR 1.86, 95% CI 0.96 to 3.62, I 2  = 45%; MD 3.98, 95% CI 3.07 to 4.88, I 2  = 4%), rather those taking low doses (adjusted RR 1.38, 95% CI 0.94 to 2.02, I 2  = 59%; MD 1.46, 95% CI -0.79 to 3.70, I 2  = 82%)., Conclusions: Glucocorticoids treatment delayed viral clearance in COVID-19 patients of taking high doses or medium doses, rather in those of taking low doses of glucocorticoids., (© 2021. The Author(s).)

Previous studies of brain structural abnormalities in attention-deficit/hyperactivity disorder (ADHD) samples scarcely excluded comorbidity or analyzed them in subtypes. This study aimed to identify neuroanatomical alterations related to diagnosis and subtype of ADHD participants without comorbidity. In our cross-sectional analysis, we used T 1 -weighted structural MRI images of individuals from the ADHD-200 database. After strict exclusion, 121 age-matched children with uncomorbid ADHD (54 with ADHD-inattentive [iADHD] and 67 with ADHD-combined [cADHD]) and 265 typically developing control subjects (TDC) were included in current investigation. The established method of voxel-based morphometry (VBM8) was used to assess global brain volume and regional grey matter volume (GM). Our results showed that the ADHD patients had more regional GM in the bilateral thalamus relative to the controls. Post hoc analysis revealed that regional GM increase only linked to the iADHD subtype in the right thalamus and precentral gyrus. Besides, the right thalamus volume was positively related to inattentive severity in the iADHD. There were no group differences in global volume. Our results provide preliminary evidence that cerebral structural alterations are tied to uncomorbid ADHD subjects and predominantly attribute to iADHD subtype. Furthermore, the volume of the right thalamus may be relevant to inattentive symptoms in iADHD possibly related to a lack of inhibition of irrelevant sensory input., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To investigate the clinical application effect of latissimus dorsi muscle flap in reconstruction of muscle strength around shoulder after electric burns. Methods: From March 2014 to September 2020, 13 patients with electric burns and severe injury around shoulder were admitted to the First Affiliated Hospital of Air Force Medical University, including 11 males and 2 females, aged 19-55 years. A retrospective observational study was conducted. The left upper limbs were injured in 8 cases, and the right upper limbs were injured in 5 cases, all with eschar wounds of Ⅲ-Ⅳ degree. Among which, there were biceps defects in 6 cases, deltoid defects in 3 cases, triceps defects in 2 cases, and composite defects of multiple muscles around shoulder in 2 cases. The surgery was carried out in two stages. In stage Ⅰ, debridement and exploration of electric burn wounds around shoulders were conducted to preserve local tissue and save the limb as much as possible on the premise of guaranteeing the stability of the body condition. After the last debridement, the wound area was from 10 cm×6 cm to 40 cm×15 cm, the muscle defect area was from 8 cm×4 cm to 19 cm×12 cm, and the humerus was exposed in 7 patients. In stage Ⅱ, according to the residual limb defect degree, muscle reconstruction around shoulder was conducted with the latissimus dorsi muscle flap, and area of the latissimus dorsi muscle flap was 15 cm×6 cm to 20 cm×18 cm. The residual wounds were repaired with autologous split-thickness skin grafts of head, and the donor sites of muscle flaps were sutured directly. The survivals of the muscle flaps and wounds closure post operation, and the appearances of the donor sites and recipient sites during follow-up were observed. At the last follow-up, the shoulder joint function was evaluated using the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association, and the satisfaction degrees of patients for appearance and function recoveries of shoulder were investigated by self-made questionnaire with reference to the concise test scoring system of shoulder joint. Results: All of the 13 muscle flaps around shoulder survived after surgery. Two patients had residual wounds in the skin grafting area, the wound in one of the patients was healed after dressing change, and the wound in the other 1 patient was healed with the second autologous split-thickness skin grafting on head after dressing change. During follow-up of 6 to 18 months for all the patients, the muscle flaps of patients were full in appearance and not bloated, and atrophic scar in the repaired area was soft in texture and closed with normal skin around. Linear suture scars were left in the donor sites of muscle flaps, which did not affect the overall appearance. At the last follow-up, the active abduction range of the shoulder joint was 60-90°, upward lift on 120-180°, muscle strength recovered to level Ⅳ and above in 8 cases and to level Ⅲ in 5 cases, and the shoulder joint function was evaluated as excellent in 8 cases and good in 5 cases; 10 patients were very satisfied and 3 patients were satisfied with the appearance and function recovery of the shoulders. Conclusions: The application of latissimus dorsi muscle flap provides a better choice for the muscle strength reconstruction around shoulder after electric burns, with good appearance of the operative areas and ideal prognosis of upper limb function.

The difficulties and challenges of applying the HLH-2004 diagnostic criteria to early identification and diagnosis of haemophagocytic lymphohistiocytosis have been fully addressed in previous studies. However, the distribution of the diagnostic time lag of haemophagocytic lymphohistiocytosis and related patient characteristics remain unclear. This study investigated the time lags between symptom onset and diagnosis and between hospital admission and diagnosis among pediatric patients with haemophagocytic lymphohistiocytosis, and identified factors that associated with a shorter or longer diagnostic time lag. The cohort of patients with haemophagocytic lymphohistiocytosis was drawn from a tertiary children's hospital and consisted of 122 pediatric patients. The distributions of symptom-to-diagnosis and admission-to-diagnosis time lags were assessed. Clinical characteristics within 48 h of admission and the fulfillment of HLH-2004 diagnostic criteria were compared among admission-to-diagnosis time lag categories. Logistic regression analyses were conducted to identify factors associated with an admission-to-diagnosis time lag >3 days. The median interval from first symptom onset to HLH diagnosis was 12 days (range 4-71 days) and the median interval from hospital admission to HLH diagnosis was 2 days (range 0-23 days). The following factors were negatively associated with admission-to-diagnosis > 3 days: Epstein-Barr virus infection; admission through pediatric intensive care unit; diagnosis established without NK-cell activity and soluble CD25 tests; the performance of all readily available diagnostic tests for HLH (within 48 and 72 h); concurrent fever, splenomegaly, and cytopenias within 48 h; hemophagocytosis, hypertriglyceridemia and/or hypofibrinogenemia within 48 h; and elevated ferritin, total bilirubin, alanine aminotransferase, and prothrombin time within 48 h. Our findings suggest that performance of adequate diagnostic tests for HLH is essential for early diagnosis of HLH. Once suspected, immediate and adequate diagnostic tests for HLH should be arranged for PICU patients. Improvements in diagnostic procedures and monitoring plans are needed to promote early diagnosis of HLH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Yan, Xiao, Zhang, Huang, Xiang, Zheng, Yao, Zang, Zhu, Li and Lu.)

Background: Type 2 diabetes mellitus (T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia. The mechanisms of diabetes-associated cognitive dysfunction (DACD) have not been fully elucidated to date. Some studies proved lower cerebral blood flow (CBF) in the hippocampus was associated with poor executive function and memory in T2DM. Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor (VEGF) expression and CBF changes in humans and animal models. In this study, we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional (3D) arterial spin labeling (3D-ASL) and VEGF expression in the hippocampus., Aim: To assess the correlation between CBF (measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM., Methods: Forty Sprague-Dawley male rats were divided into control and T2DM groups. The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM. Cognitive function was assessed using the Morris water maze experiment. The CBF changes were measured by 3D-ASL magnetic resonance imaging. VEGF expression was determined using immunofluorescence., Results: The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group. The total distance traveled was longer in the T2DM group; also, the platform was crossed fewer times. The percentage of distance in the target zone significantly decreased. CBF decreased in the bilateral hippocampus in the T2DM group. No difference was found between the right CBF value and the left CBF value in the T2DM group. The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value. The escape latency negatively correlated with the CBF value. The number of rats crossing the platform positively correlated with the CBF value., Conclusion: Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD. CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: It had been reported that the increase in the prevalence of childhood overweight and obesity in several developed countries over the decade was largely a consequence of changes in the upper end of the body mass index (BMI) distribution. We speculated that the change in BMI distribution among Chinese children is different from that in developed countries. Therefore, we investigated the changes in the BMI distribution among urban children in Changsha, China., Methods: A secondary data analysis of the 2002 and 2018 Annual Survey on Students' Constitution and Health from Yuhua District, Changsha City, China was performed. The BMI distribution of children aged 6-15 years (n=72,061) was examined by calculating the BMI value at 5th, 50th, 85th, and 95th percentiles. Differences in the BMI value at the 5th, 50th, 85th, and 95th percentiles between 2002 and 2018 according to age and sex were calculated., Results: From 2002 to 2018, the standardized rate of underweight decreased from 6.9% to 3.4%, whereas that of obesity increased from 6.1% to 13.8%. The BMI of the population increased over the 16-year period. The greatest change between the years was seen in the 85th percentile, and moderate changes were seen in the 5th and 50th BMI percentiles. Also, the greatest changes in the BMI percentiles were evident at age 12-14 years., Conclusions: The whole spectrum of BMI distribution among school-aged children shifted over the 16-year study period, although the increases were more marked in the upper than lower percentiles. Health professionals and health policymakers should develop strategies and interventions aimed at preventing adverse health effects caused by this change., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-20-305). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Physical activity participation in children declines with age. It is not clear yet whether the age-related trends vary by weight status. This study is aimed at investigating the association between physical activity participation and age among children with healthy weight, overweight, or obesity, using data from the 2016-2017 National Survey of Children's Health (NSCH). Physical activity participation was evaluated by days participated in physical activity for at least 60 minutes out of 7 days. Weight status was categorized from body mass index (BMI) percentiles. Data were analyzed on 33,056 US children age 10-17 years. The percentages of been active 0 day out of 7 days in BMI5th < 85th (healthy weight), 85th < 95th (overweight), and ≥95th percentile (obese) groups were 8.9%, 11.5%, and 18.2%, respectively. Among all groups, been active 0 day out of 7 days was positively associated with age, while the strongest associations were observed in the BMI85th < 95th group (age 17 years vs. age 10 years: OR = 7.48, p < 0.0001). Older age was significantly associated with been active less than 4 days out of 7 days in the BMI5th < 85th and 85th < 95th groups, but those associations were attenuated in the BMI ≥ 95th group. This study found that physical activity participation was inversely associated with age among children with healthy weight, overweight, or obese, and the association was strongest among children with overweight and weakest among children with obesity. Interventions aimed at promoting physical activity among children should take these patterns of association into account., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Xun Li et al.)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare and life-threatening disorder. Early mortality remains significantly high among patients with HLH. Our aim was to investigate clinical features and risk factors associated with 7-day and 30-day mortality among pediatric HLH patients. We retrospectively collected medical records of patients with discharge diagnosis of HLH between August 2014 and October 2018 from a tertiary children's hospital in China. The main outcome measures were the 7-day and 30-day outcome after hospital admission. The associations between symptoms, concomitant diagnoses, laboratory test results, and the risk of 7-day and 30-day mortality were examined., Results: Among 160 pediatric HLH patients, 18 (11.3%) patients were deceased within 7 days after admission, and 46 (28.8%) patients were deceased within 30 days. The identified strong risk factors (OR > 10 and p < 0.05) for 30-day mortality were myocardial damage, severe pneumonia, respiratory failure, coagulopathy, gastrointestinal disorder, and multiple organ dysfunction syndrome (MODS). Factors strongly associated with 7-day mortality were sepsis, myocardial damage, shock, and respiratory failure. All patients deceased within 7 days developed hepatic dysfunction, coagulopathy, and MODS., Conclusions: The identified risk factors could help to stratify patients with high risk of early death, and need to be considered in the development of treatment protocols. As early mortality of HLH remains high, studies are needed to investigate how to initiate adequate HLH-directed treatment strategies for patients at higher risk of early death.

Pediatric palliative care refers to the comprehensive physical, mental, and psychological care provided to the children with life-threatening diseases, as well as support for their families, aiming to provide the best quality of life for children and their families. In the face of the large population of children in China, the increasing demand for palliative care services and the insufficient development of related service resources are existential problems in the field of palliative care for children in China. This article reviews the implementation and current development status of pediatric palliative care in China.

Background: Primary lacrimal sac melanoma is an extremely rare condition with fewer than 50 cases reported so far. Clinically, its symptoms resemble those of dacryocystitis, leading to frequent misdiagnosis. During diagnosis, imaging examination is often performed to differentiate tumors from inflammation. In this report, we present a case of primary lacrimal sac melanoma and summarize the CT and MRI characteristics of lacrimal sac melanoma., Case Presentation: We report a 50-year-old female patient who had undergone a dacryocystectomy for the left lacrimal sac mass. Postoperative pathological examination confirmed the presence of primary malignant melanoma. Three months later, a lump in the lacrimal sac area was found. The patient underwent CT and MR examinations. CT scan demonstrated a partially well-defined soft mass in the fossa of left lacrimal sac extending into the nasolacrimal duct and anterior ethmoid sinus. MRI revealed an intermediate signal intensity on T1 and iso-or hyper-signal on T2 weighted images. Histopathological examination on biopsy confirmed recurrence of primary lacrimal sac melanoma., Discussion and Conclusions: None has described the CT and MR findings of primary lacrimal sac melanoma so far. Typically, MR images show hyperintensity signal on T1-weighted images and hypointense signal on T2-weighted images owing to the paramagnetic properties of melanin. In contrast to previous reports and the present case, most cases do not present these typical signals. Thus, reporting such radiological findings is important to create awareness on variant images of primary lacrimal sac melanoma. This will reduce misdiagnosis and mistreatment.

Patients with hemophagocytic lymphohistiocytosis (HLH) have high risk of early mortality. The purpose of this study was to test the hypothesis that the elevated level of serum myoglobin among patients with HLH is associated with disease severity and increased risk of mortality. We retrospectively investigated the serum myoglobin levels from 155 pediatric patients diagnosed with HLH in the Hunan Children's Hospital, China. The levels of myoglobin and creatine kinase at hospital admission among non-survivors and survivors were compared. The myoglobin level was dichotomized for the estimation of hazard ratio (HR) for mortality. Patients who died within 7 and 30 days of hospitalization had significantly higher myoglobin levels than did survivors (p < 0.05). The myoglobin level was negatively associated with the days of survival among non-survivors (Spearman correlation coefficient = - 0.29, p = 0.04). An elevated myoglobin level (> 90 ng/mL) was significantly associated with increased mortality (unadjusted HR = 2.66, 95%CI: 1.41, 5.00, p = 0.0024) and persisted after adjusting for age, Epstein-Barr virus infection, admission department, acute kidney injury, myocardial damage, and shock. In conclusion, an elevated serum myoglobin level was associated with increased risk of early death among pediatric patients with HLH, suggesting the potential of myoglobin to be used as a reference indicator for monitoring and managing of HLH.

Background: Acute uncomplicated lower urinary tract infection (UTI) is one of the most common bacterial infections. Patients usually present with dysuria, urinary urgency, urinary frequency, and suprapubic pain or tenderness. Approximately 150 million people are diagnosed with UTI each year worldwide. The high recurrence rate of lower UTI is a common problem of clinical treatment. The misuse of antibiotics has led to the emergence of a number of resistant bacterial strains. Thus, traditional Chinese medicine is considered as an alternative option for treating acute uncomplicated lower UTI. Thus, this study aims to evaluate the efficacy and safety of Sanjin tablets (SJT) for the treatment of acute uncomplicated lower UTI, explore whether SJT can reduce or substitute the use of antibiotics, and reduce the recurrence rate in the treatment of acute uncomplicated lower UTI., Methods/design: In this study, a randomized, double-blind, double-dummy, parallel control of positive drug, multicenter clinical study will be established. A total of 252 patients with acute uncomplicated lower UTI (syndrome of dampness-heat in the lower jiao) will be randomly allocated in the ratio of 1:1:1 to three groups: experimental group; control group 1; and control group 2. The experimental group receives Sanjin tablets plus levofloxacin tablets (LT) placebo; the control group 1 receives LT plus SJT placebo; and the control group 2 receives SJT plus LT on the first five days, SJT plus LT placebo on the last two days. Each group will be treated for seven days and followed-up 1-2 times. The primary outcome measures of effective rate and recurrence rate are symptoms. Secondary outcome measures of effective rate and recurrence rate are the urine leukocytes, bacteriology examination, and safety assessment. Outcomes will be assessed at baseline and after treatment., Discussion: This study protocol will provide the research data of efficacy and safety of SJT for the treatment of acute uncomplicated lower UTI. The first aim is to determine whether Sanjin tablets can reduce the use of antibiotics; the second aim is to determine whether Sanjin tablets can substitute the use of antibiotics. The recurrence rate will be assessed after cured to determine whether SJT can reduce the recurrence rate. The results of this study will improve the rational use of drugs, especially the rational application of antibiotics. It will also enable safety evaluation from laboratory indices and adverse events, which will provide reliable evidence for clinical treatment., Trial Registration: ClinicalTrials.gov, NCT03658291 . Registered on 4 September 2018.

Objective: To investigate the clinicopathological characteristics and improve the clinical treatment of prostatic small-cell carcinoma (PSCC)., Methods: We reported 2 cases of PSCC derived from prostate cancer after treated by androgen blockade and prostate electrotomy and reviewed the relevant literature., Results: Two patients with PSA elevation were diagnosed with prostate cancer by prostatic puncture biopsy and treated by maximum androgen blockade, which reduced their total PSA to the normal level. Later, due to difficult urination, they both underwent prostate electrotomy, followed by chemotherapy or radiotherapy for PSCC confirmed by postoperative pathology. Nevertheless, they died at 8 to 9 months after the discovery of PSCC., Conclusions: PSCC can derive from prostate cancer after treatment, which may be attributed to the pathological mutation induced by long-term endocrine therapy. PSCC is more malignant than prostate cancer, and its prognosis is poor.

Background: The association between serum C-peptide concentration and prostate cancer remains unexplored. Therefore, we conducted a meta-analysis to assess whether C-peptide serum concentrations are associated with increased prostate cancer risk., Methods: Several databases were searched to identify relevant original research articles published before November 2017. Random-effects models were used to summarize the overall estimate of the multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (CIs)., Results: Nine observational studies involving 11,796 participants were identified. The findings of the meta-analysis indicated that the association between serum C-peptide concentration and prostate cancer was not significant (OR: 1.15, 95% CI: 0.85-1.54; for highest versus lowest category C-peptide concentrations, P = .376). The associations were inconsistent, as indicated by subgroup analyses., Conclusion: Although our findings provided no support for the hypothesis that serum C-peptide concentration is associated with excess risk of prostate cancer, people must pay attention to this aspect and increase physical activity or modify dietary habits to constrain insulin secretion, which possibly lead to decreased incidence of prostate cancer. Hence, well-designed observational studies involving different ethnic populations are still needed.

Objective: To explore the inhibitory effect of polyphyllin Ⅰ (PPⅠ) on the proliferation of castration-resistant prostate cancer PC3 cells and its molecular mechanism., Methods: We cultured human prostate cancer PC3 cells in vitro and treated them with PPⅠ at the concentrations of 0 (blank group), 0.4, 0.8, 1.2, 1.6, 2.0, and 2.4 μmol/L for 24, 48, and 72 hours, respectively. Then we detected the proliferation of the cells by MTT assay, measured their apoptosis by flow cytometry, and determined the expressions of p-ERK1/2, ERK1/2, NF-κB/p65 and DNMT1 proteins as well as the level of NF-κB/p65 in the cells additionally treated with the ERK1/2 inhibitor SP600125 by Western blot., Results: Compared with the blank control group, the PPⅠ-treated PC3 cells showed a concentration- and time-dependent reduction of the survival rate (1.00 ± 0.00 vs 0.85 ± 0.05, P < 0.01) at 0.4 μmol/L after 48 hours of intervention, concentration-dependent early apoptosis at 0.8 μmol/L (4.83 ± 0.95 vs 13.83 ± 2.97, P < 0.01), time-dependent increase of the expressions of p-ERK1/2 (1.00 ± 0.00 vs 1.73 ± 0.17, P < 0.01) and ERK1/2 (1.00 ± 0.00 vs 1.36 ± 0.12, P < 0.01) at 2 hours, and concentration-dependent decrease of the expressions of NF-κB/p65 and DNMT1 at 1.2 μmol/L (1.00 ± 0.00 vs 0.78 ± 0.10 and 0.63 ± 0.06, P < 0.01) and 1.6 μmol/L (1.00 ± 0.00 vs 0.67 ± 0.11 and 0.52 ± 0.09, P<0.01). Inhibition of ERK1/2 phosphorylation with PD98059 markedly reversed PPⅠ-induced decrease of the NF-κB/p65 expression as compared with that in the PPⅠ group (0.86 ± 0.18 vs 0.43 ± 0.09, P < 0.05)., Conclusions: PPⅠ induces the early apoptosis and suppresses the proliferation of PC3 cells, probably by activating the ERK1/2 pathway and inhibiting the expressions of the NF-κB/p65 and DNMT1 proteins.

Accumulating evidence indicates interleukin-1 (IL-1) is a critical mediator of inflammatory responses in ischemic stroke (IS). The aim of this study was to investigate whether rs3783553 in the 3'-untranslated region of IL-1A was associated with the risk of IS. In this hospital-based case-control study, we genotyped the rs3783553 using polymerase chain reaction in 316 patients with IS and 332 age, sex, and ethnicity-matched controls. Plasma level of IL-1α was measured by enzyme-linked immunosorbent assay. The relative luciferase activities were measured by the Dual Luciferase assay system. The presence of ins/ins genotype was associated with higher odds ratios (ORs) of IS compared with del/del genotype (ins/ins vs del/del: adjusted OR 1.77, 95% confidence interval [CI] 1.06-2.98; recessive model: adjusted OR 1.69, 95% CI 1.06-2.70). The higher risk of IS was also observed in allele comparison (adjusted OR 1.29, 95% CI 1.00-1.65). Multivariate logistic regression analysis showed that age, hypertension, total cholesterol, triglyceride, low-density lipoprotein, and rs3783553ins/ins genotypes were independent risk factors for IS. Plasma level of IL-1α was higher among IS patients compared with controls (P = .03). Notably, IS patients with the TTCA/TTCA genotype had a higher level of IL-1α compared with those with the del/del genotype (P = .01). Luciferase reporter assay showed that the vector containing the TTCA del allele exhibited a reduced transcriptional activity in the presence of miR-122 and miR-378. These findings indicate that IL-1A rs3783553 ins/ins genotype may increase the susceptibility to IS, possibly by interrupting the binding site of miR-122 and miR-378.

Authors raised that staging based strategies and practice of integrative medicine (IM) by combining syndrome typing and disease identification, and choosing suitable measures in accordance with different persons and seasonal conditions after more than ten years' clinical practice and researches. Radical operation as prior (as evil eliminating) and strengthening vital qi in perioerative period are best strategy for promoting rapid rehabilitation of early stage prostate cancer patients. Strengthening body resistance to eliminate evil was used in treating advanced prostate cancer patients. For example, a comprehensive treatment program for hormone-dependent patients was combined with endocrinotherapy and Chinese herbs for synergisic efficacy-enhancing actions. In this way, these patients' quality of life (QOL) were improved and time to castration resistant prostate cancer (CRPC) was delayed, even some patients were clinically cured. There are lack of effective medicines and methods for CRPC patients. Greatly tonifying original qi is mainly used for improving their clinical symptoms and prolonging survivals. Practice has proved staging based strategies and practice of IM has favorable advantages in treating prostate cancer, especially showing prospect in prolonging survival and postponing progression of advanced prostate cancer patients. Besides, it also could provide beneficial considerations and inspiration for combination of syndrome typing and disease identification.

Background: Papillary fibroelastoma (PFE) is a rare primary cardiac neoplasm that is usually discovered incidentally at autopsy or during cardiac surgery. PFE combined with rheumatic heart disease (RHD) is extremely rare, and only a few cases have been reported. Additionally, the growth rate of the tumor is unknown., Case Presentation: Here, we present a very rare case of PFE of the aortic valve combined with RHD, which were identified in a female patient who survived for 5 years without surgical intervention, and who subsequently underwent successful surgical treatment., Conclusions: PFEs may be generally slow-growing tumors, however, the better treatment of choice may be surgery because it produces good curative effects with very low risk of complications, while preventing serious disease consequences.

Objective: To systematically evaluate the efficacy and safety of kidney-tonifying traditional Chinese medicine in the treatment of male infertility., Methods: Based on the principles and methods of Cochrane systematic reviews, we searched CNKI, VIP, and Wanfang databases from inception to December 2012 for randomized controlled clinical trials addressing the treatment of male infertility with kidney-tonifying traditional Chinese medicine. According to the inclusion and exclusion criteria and retrieval strategies, we extracted the data, evaluated the quality of the included literature, and conducted meta-analysis using the RevMan 5. 2 software., Results: Twenty trials involving 2,272 patients were included, and the sample size of each study was from 60 to 270 cases. All the studies were graded as of poor quality, with Jadad scores of no more than 3 points. The results of meta-analysis showed that the total effectiveness rate of traditional Chinese medicine versus Western medicine on male infertility was RR = 1.71, 95% CI 1.19-2.47, and that of Chinese-Western combined therapy versus Western medicine was RR = 1.15, 95% CI 1.01-1.30. Both traditional Chinese medicine and Chinese-Western combined therapy showed a significantly better total effectiveness than Western medicine alone in improving the pregnancy rate without serious adverse reactions., Conclusion: Due to the poor methodological quality and high heterogeneity of the included studies, the evidence for the efficacy and safety of kidney-tonifying traditional Chinese drugs in the treatment of male infertility is of but limited value, and further validation is needed by more high-quality studies.

Libman-Sacks endocarditis (LSE), characterized by verrucous vegetations formation, is a typical cardiac manifestation of autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It primarily leads to lesions of cardiac valves and mostly involved valves are mitral and aortic, but isolated tricuspid valve involvement is exceptional. Here we reported a 20-years-old female with past SLE history suffered from acute right heart failure caused by multiple tricuspid vegetations and valve regurgitation. The patient recovered following tricuspid valve replacement with a bioprosthesis. Transesophageal echocardiography(TEE), especially real time 3-dimensional (RT3D) TEE provide a better imaging modality for assessing cardiac valvular involvement of LSE. For patients with active SLE/APS course, uncontrolled systemic inflammation may made it difficult for surgical exposure and suture. The durability of bioprosthesis for this patient and the prosthesis selection for tricuspid LSE both need further follow-up and more clinical investigation.

Survival motor neuron (SMN) is the determining factor in spinal muscular atrophy, the most common genetic cause of childhood mortality. We have previously found that SMN regulates stem cell division, proliferation and differentiation in Drosophila. However, it is unknown whether a similar effect exists in vertebrates. Here, we show that SMN is enriched in highly proliferative embryonic stem cells (ESCs) in mice and reduction of SMN impairs the pluripotency of ESCs. Moreover, we find that SMN reduction activates ERK signaling and affects neuronal differentiation in vitro. Teratomas with reduced SMN grow more slowly and show weaker signals of neuronal differentiation than those with a normal level of SMN. Finally, we show that over-expression of SMN is protective for ESCs from retinoic acid-induced differentiation. Taken together, our results suggest that SMN plays a role in the maintenance of pluripotent ESCs and neuronal differentiation in mice.

The objective of this study is to quantitatively analyze the predictive strength among the conventional serological tumor biomarkers for gastric cancer in Chinese population. Thirty-three hospital-based case-control studies were searched out through Chinese databases and PubMed during 1999-2009. Gastric cancer cases and healthy volunteers or benign gastric diseases controls were detected of any of serological CA724, CA242, CEA, CA199, CA125, or CA153. Areas under the curve (AUC) and optimal Q indexes of summary receiver operating characteristics (sROC) curves were quantitatively compared. The summary positive and negative likelihood ratios (sLR + and sLR-) were pooled. Totally, 2,390 gastric cancer cases and 2,893 controls were analyzed. CA724 and CA242 both had the greatest AUCs (0.88), respectively, followed by the combination CA724 + CEA + CA199 (0.85), CA125 (0.82), CEA (0.80), and CA199 (0.76), but all of them had no statistical significance to CA153 (negative control) by Z tests, possibly due to relatively great standard errors. The results of Q index analyses were similar to those of AUCs, that CA724 and CA242 had the optimal strength. The sLR + of CA724 (16.08, 95 % confidence interval (CI) 7.86-32.86) or CA242 (11.03, 95 % CI 7.12-17.08) was strong to judge the gastric cancer status based on its positive result. The combination of CA724 + CEA + CA199 had the prior sLR- (0.33, 95 % CI 0.25-0.43) to the others. Serological CA724 or CA242 has predictive effect for screening gastric cancer and can be recommended into the screening program of population-based or symptomatic cases. However, prospective epidemiological studies are required before confirmative conclusion.

Purpose: Percutaneous endoscopic interlaminar discectomy (PEID) is a widely used minimally invasive procedure which shows satisfying outcomes in the adult population. However, pediatric lumbar disc herniations (PLDH) occur in growing spines and are less related to degeneration, which makes them different from the adult disc herniations. This study evaluates the clinical outcomes of PEID in treating PLDH., Methods: A prospect study was done in the period from June 2010 to December 2012, which included 29 consecutive pediatric patients with a mean age of 16.4 years (range, 13 to 18 years) who underwent PEID for single level lumbar disc herniation. The following measuring tools were used: visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and Macnab criteria., Results: There were no severe complications such as dural tear or nerve root damage found in our study. The mean follow-up period was 19.7 months. The VAS score for leg and back pain decreased dramatically at 1 day postoperatively and kept decreasing until the follow-up visit at 3 months postoperatively, when it became stable at a low level. ODI kept improving until the follow-up visit at 6 months postoperatively when it reached a stable low level. Of the patients, 91% reported no longer having leg pain and 9% had occasional leg pain at last follow-up., Conclusions: PEID shows a satisfying outcome with a minimal rate of complications. It has the advantages of minimal traumatization and scar formation and is a safe and effective treatment for PLDH.