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Objectives: In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +)., Methods: The triage performance of liquid-based cytology (LBC) and the PAX1 m /JAM3 m test for detecting CIN3 + were compared., Results: In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1 m /JAM3 m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1 m /JAM3 m ( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1 m /JAM3 m (+). Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1 m /JAM3 m (+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1 m /JAM3 m (+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%)., Conclusions: In non-16/18 hrHPV(+) women, PAX1 m /JAM3 m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity., (© 2024. The Author(s).)

Coiled-coil domain containing 88C (CCDC88C) is a component of non-canonical Wnt signaling, and its dysregulation causes colorectal cancer metastasis. Dysregulated expression of CCDC88C was observed in lymph node metastatic tumor tissues of breast cancer. However, the role of CCDC88C in breast cancer metastasis remains unclear. To address this, the stable BT549 and SKBR3 cell lines with CCDC88C overexpression or knockdown were developed. Loss/gain-of-function experiments suggested that CCDC88C drove breast cancer cell motility in vitro and lung and liver metastasis in vivo. We found that CCDC88C led to c-JUN-induced transcription activation. Overlapping genes were identified from the genes modulated by CCDC88C and c-JUN. CEMIP, one of these overlapping genes, has been confirmed to confer breast cancer metastasis. We found that CCDC88C regulated CEMIP mRNA levels via c-JUN and it exerted pro-metastatic capabilities in a CEMIP-dependent manner. Moreover, we identified the CCDC88C as a substrate of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6). GALNT6 was positively correlated with CCDC88C protein abundance in the normal breast and breast cancer tissues, indicating that GALNT6 might be associated with expression patterns of CCDC88C in breast cancer. Our data demonstrated that GALNT6 maintained CCDC88C stability by promoting its O-linked glycosylation, and the modification was critical for the pro-metastatic potential of CCDC88C. CCDC88C also could mediate the pro-metastatic potential of GALNT6 in breast cancer. Collectively, our findings uncover that CCDC88C may increase the risk of breast cancer metastasis and elucidate the underlying molecular mechanisms., (© 2024. The Author(s).)

Objective: The present study aimed to investigate the long-term effects of parent-child separation during infancy and early childhood on depression, social relationships including parent-child and peer relationships, and academic performance during adolescence and early adulthood., Methods: Data from the China Family Panel Studies (CFPS) were analyzed, which included a sample of 3829 children aged 4-15 years from 25 provinces over a period of 8 years. The study examined the association between early parent-child separation and outcomes related to depression, social and academic performance, comparing outcomes between individuals with and without early separation experiences. A series of subgroup analyses were conducted to further explore these associations., Results: Parent-child separation lasting 3 months or longer was found to be associated with moderate to severe levels of depression and impaired social relationships during adolescence and early adulthood, particularly among males, adolescents, urban dwellers, and those with less educated mothers. Children who experienced parent-child separation for 3 months or longer showed a positive correlation between separation duration and depression. Short-term separations under 3 months did not show this association. The duration of separation also had a negative correlation with parent-child and peer relationships, as well as academic performance., Conclusion: Early parent-child separation has significant adverse effects on the mental health, social and academic performance of adolescents and early adulthood, especially among males, adolescents, urban residents, and those with lower maternal education. The severity of depression was found to be related to the duration of separation, highlighting the importance of minimizing separation to less than 3 months for children under the age of 3. These findings underscore the critical role of early parental care and the need for targeted interventions for high-risk populations., (© 2024. The Author(s).)

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. Intestinal inflammation involved in the pathogenesis of PD, but the underlying mechanism is not fully understood. Citrobacter rodentium (C.R) is a gram-negative bacterium that can be used to induce human inflammatory bowel disease in mice. Here, we investigated whether the proinflammatory effects caused by C.R infection initiate PD-like injury and/or exacerbate PD pathology and extensively studied the underlying mechanism. Mice were gavaged once with C.R and monitored for several pathological features at 9 days post infection. The results showed that C.R delivery in mice induced IBD-like symptoms, including significant weight loss, increased fecal water content, an impaired intestinal barrier, intestinal hyperpermeability and inflammation, and intestinal microbiota disturbances. Notably, C.R infection modified dopamine (DA) metabolism in the brains of both male and female mice. Subsequently, a single high dose of MPTP or normal saline was administered at 6 days post infection. At 3 days after MPTP administration, the feces were collected for 16 S rRNA analysis, and PD-like phenotypes and mechanisms were systemically analyzed. Compared with C.R or MPTP injection alone, the injection of C.R and MPTP combined worsened behavioral performance. Moreover, such combination triggered more severe dopaminergic degeneration and glial cell overactivation in the nigrostriatal pathway of mice. Mechanistically, the combination of C.R and MPTP increased the expression of TLR4 and NF-κB p65 in the colon and striatum and upregulated proinflammatory cytokine expression. Therefore, C.R infection-induced intestinal inflammation can impair dopamine metabolism and exacerbate PD pathological processes., (© 2024. The Author(s).)

Background: Existing researches on nurses' work engagement and job burnout have mostly stayed at the individual level, and limited researches test the cross-level effects of psychosocial safety climate (PSC). The study aimed to explore the cross-level mediating effect of organization-based self-esteem (OBSE) and the moderating effect of psychological detachment between the relationship of PSC and work engagement and job burnout in nurses., Methods: The cross-sectional study was conducted during November to December 2022 at a tertiary hospital in a northeastern province of China. Data was collected from 1832 nurses through an online questionnaire. Correlation analyses and hierarchical linear modeling were used to test study hypotheses., Results: The results showed that PSC was positively associated with work engagement, and negatively associated with job burnout. OBSE mediated the effect of PSC on work engagement, as well as job burnout. Additionally, psychological detachment played a moderating role between PSC and work engagement, but no moderating effect was found between PSC and job burnout., Conclusions: PSC at the organizational level increases work engagement and reduces job burnout by stimulating nurses' high levels of OBSE. Psychological detachment, as a situational factor, enhances the positive influence of PSC on work engagement. The implementation of measures to improve the PSC levels of the organization, and the levels of OBSE and psychological detachment among nurses could help to promote their good work performance., (© 2024. The Author(s).)

Background: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study., Methods: A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways' activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein-protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed., Results: In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP., Conclusion: We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP., (© 2024. The Author(s).)

Neuroinflammation is one of the core pathological features of Parkinson's disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate immune memory, resulting in an enhanced or suppressed immune response to second stimuli, which is known as innate immune training and innate immune tolerance, respectively. In this study, LPS was used to establish in vitro and in vivo models of innate immune memory. Microglia-specific Hif-1α knockout mice were further employed to elucidate the regulatory role of HIF-1α in innate immune memory and MPTP-induced PD pathology. Our results showed that different paradigms of LPS could induce innate immune training or tolerance in the nigrostriatal pathway of mice. We found that innate immune tolerance lasting for one month protected the dopaminergic system in PD mice, whereas the effect of innate immune training was limited. Deficiency of HIF-1α in microglia impeded the formation of innate immune memory and exerted protective effects in MPTP-intoxicated mice by suppressing neuroinflammation. Therefore, HIF-1α is essential for microglial innate immune memory and can promote neuroinflammation associated with PD., (© 2024. The Author(s).)

Background: The molecular targets and associated mechanisms of hepatocellular carcinoma (HCC) have been widely studied, but the roles of PDZK1 in HCC are unclear. Therefore, the aim of this study is to explore the role and associated mechanisms of PDZK1 in HCC., Results: It was found that the expression of PDZK1 in HCC tissues was higher than that in paired paracancerous tissues. High expression of PDZK1 was associated with lymph node metastasis, degree of differentiation, and clinical stage. Upregulation of PDZK1 in HCC cells affected their proliferation, migration, invasion, apoptosis, and cell cycle, and also induced PI3K/AKT activation. PDZK1 is a downstream target gene of miR-101-3p. Accordingly, increase in the expression of miR-101-3p reversed the promotive effect of PDZK1 in HCC. Moreover, PDZK1 was found to accelerate cell proliferation and promote the malignant progression of HCC via the PI3K/AKT pathway., Conclusion: Our study indicated that the miR-101-3p/PDZK1 axis plays a role in HCC progression and could be beneficial as a novel biomarker and new therapeutic target for HCC treatment., (© 2024. The Author(s).)

Objective: To determine whether non-invasive prenatal testing is an alternative testing option to preimplantation genetic testing (PGT) in pregnant patients., Methods: This was a retrospective study of the clinical outcomes of patients who underwent PGT and invasive or non-invasive pregnancy testing after euploid blastocyst transfer at our IVF centre between January 2017 and December 2022., Results: In total, 321 patients were enrolled in this study, 138 (43.0%) received invasive pregnancy testing, and 183 (57.0%) patients underwent non-invasive testing. The mean age of the patients in Group 2 was higher than that of the patients in Group 1 (35.64 ± 4.74 vs. 31.04 ± 4.15 years, P < 0.001). The basal LH and AMH levels were higher in Group 1 than in Group 2 (4.30 ± 2.68 vs. 3.40 ± 1.88, P = 0.003; 5.55 ± 11.22 vs. 4.09 ± 3.55, P = 0.012), but the clinical outcomes were not significantly different. Furthermore, the clinical outcomes of patients undergoing invasive testing were similar to those of patients undergoing non-invasive testing with the same PGT indication., Conclusion: Our results suggest that non-invasive pregnancy testing is a suitable alternative option for detecting the foetal chromosomal status in a PGT cycle. However, the usefulness of non-invasive testing in PGT-M patients is still limited., (© 2024. The Author(s).)

Objective: Preimplantation genetic testing for monogenic disorders (PGT-M) has been used for over 20 years to detect many serious genetic conditions. However, there is still a lack of reference materials (RMs) to validate the test performance during the development and quality control of PGT-M., Method: Sixteen thalassemia cell lines from four thalassemia families were selected to establish the RMs. Each family consisted of parents with heterozygous mutations for α- and/or β-thalassemia and two children, at least one of whom carried a homozygous thalassemia mutation (proband). The RM panel consisted of 12 DNA samples (parents and probands in 4 families) and 4 simulated embryos (cell lines constructed from blood samples from the four nonproband children). Four accredited genetics laboratories that offer verification of thalassemia samples were invited to evaluate the performance of the RM panel. Furthermore, the stability of the RMs was determined by testing after freeze‒thaw cycles and long-term storage., Results: PGT-M reference materials containing 12 genome DNA (gDNA) reference materials and 4 simulated embryo reference materials for thalassemia testing were successfully established. Next-generation sequencing was performed on the samples. The genotypes and haplotypes of all 16 PGT-M reference materials were concordant across the four labs, which used various testing workflows. These well-characterized PGT-M reference materials retained their stability even after 3 years of storage., Conclusion: The establishment of PGT-M reference materials for thalassemia will help with the standardization and accuracy of PGT-M in clinical use., (© 2024. The Author(s).)

Objective: To discuss the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma., Methods: We retrospectively analyzed all cases of sigmoid sinus thrombophlebitis caused by middle ear cholesteatoma over a period of 7 years. 7 male and 2 female patients, ranging in age from 9 to 66 years, were diagnosed with sigmoid sinus thrombophlebitis by clinical presentation and radiological examination. By executing a modified mastoidectomy and tympanoplasty (canal wall-down tympanoplasty) to entirely remove the cholesteatoma-like mastoid epithelium, all patients were effectively treated surgically without opening the sigmoid sinus. All patients were treated with broad-spectrum antibiotics, but no anticoagulants were used., Results: 9 patients had otogenic symptoms such as ear pus, tympanic membrane perforation, and hearing loss. In the initial stage of the surgery, modified mastoidectomy and tympanoplasty were performed on 8 of the 9 patients. 1 patient with a brain abscess underwent puncturing (drainage of the abscess) to relieve cranial pressure, and 4 months later, a modified mastoidectomy and tympanoplasty were carried out. Following surgery and medication, the clinical symptoms of every patient improved. After the follow-up of 6 months to 7 years, 3 patients were re-examined for MRV and showed partial sigmoid sinus recovery with recanalization. 4 months following middle ear surgery, the extent of a patient's brain abscess lesions was significantly reduced. 1 patient experienced facial paralysis after surgery and recovered in 3 months. None of the patients had a secondary illness, an infection, or an abscess in a distant organ., Conclusion: The key to a better prognosis is an adequate course of perioperative antibiotic medication coupled with surgical treatment. A stable sigmoid sinus thrombus can remain for a long time after middle ear lesions have been removed, and it is less likely to cause infection and abscesses in the distant organs. The restoration of middle ear ventilation is facilitated by tympanoplasty. It is important to work more closely with multidisciplinary teams such as neurology and neurosurgery when deciding whether to perform lateral sinusotomies to remove thrombus or whether to administer anticoagulation., (© 2023. The Author(s).)

Background: Soybean is one of the most important oil crops in the world, and its protein and fat are the primary sources of edible oil and vegetable protein. The effective components in soybean protein and fat have positive effects on improving human immunity, anti-tumor, and regulating blood lipids and metabolism. Therefore, increasing the contents of protein and fat in soybeans is essential for improving the quality of soybeans., Results: This study selected 292 soybean lines from different regions as experimental materials, based on SLAF-seq sequencing technology, and performed genome-wide association study (GWAS) on the phenotype data from 2019-2021 Planted at the experimental base of Jilin Agricultural University, such as the contents of protein and fat of soybeans. Through the GLM model and MLM model, four SNP sites (Gm09&#95;39012959, Gm12&#95;35492373, Gm16&#95;9297124, and Gm20&#95;24678362) that were significantly related to soybean fat content were associated for three consecutive years, and two SNP sites (Gm09&#95;39012959 and Gm20&#95;24678362) that were significantly related to soybean protein content were associated. By the annotation and enrichment of genes within the 100 Kb region of SNP loci flanking, two genes (Glyma.09G158100 and Glyma.09G158200) related to soybean protein synthesis and one gene (Glyma.12G180200) related to lipid metabolism were selected. By the preliminary verification of expression levels of genes with qPCR, it is found that during the periods of R6 and R7 of the accumulation of soybean protein and fat, Glyma.09G158100 and Glyma.09G158200 are positive regulatory genes that promote protein synthesis and accumulation, while Glyma.12G180200 is the negative regulatory gene that inhibits fat accumulation., Conclusions: These results lay the basis for further verifying the gene function and studying the molecular mechanisms regulating the accumulation of protein and fat in soybean seeds., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Osteosarcoma (OS) is the most prevalent primary malignant bone tumor. However, single-agent chemotherapy exhibits limited efficacy against OS and often encounters tumor resistance. Therefore, we designed and constructed an integrated treatment strategy of photothermal therapy (PTT) combined with chemotherapy and used a surface-encapsulated platelet-osteosarcoma hybrid membrane (OPM) that enhances circulation time and enables OS-specific targeting., Results: The OPM functions as a shell structure, encapsulating multiple drug-loaded nanocores (BPQDs-DOX) and controlling the release rate of doxorubicin (DOX). Moreover, near-infrared light irradiation accelerates the release of DOX, thereby extending circulation time and enabling photostimulation-responsive release. The OPM encapsulation system improves the stability of BPQDs, enhances their photothermal conversion efficiency, and augments PTT efficacy. In vitro and ex vivo experiments demonstrate that BPQDs-DOX@OPM effectively delivers drugs to tumor sites with prolonged circulation time and specific targeting, resulting in superior anti-tumor activity compared to single-agent chemotherapy. Furthermore, these experiments confirm the favorable biosafety profile of BPQDs-DOX@OPM., Conclusions: Compared to single-agent chemotherapy, the combined therapy using BPQDs-DOX@OPM offers prolonged circulation time, targeted drug delivery, enhanced anti-tumor activity, and high biosafety, thereby introducing a novel approach for the clinical treatment of OS., (© 2023. The Author(s).)

Objectives: To explore an optimal model to predict the response of patients with axillary lymph node (ALN) positive breast cancer to neoadjuvant chemotherapy (NAC) with machine learning using clinical and ultrasound-based radiomic features., Methods: In this study, 1014 patients with ALN-positive breast cancer confirmed by histological examination and received preoperative NAC in the Affiliated Hospital of Qingdao University (QUH) and Qingdao Municipal Hospital (QMH) were included. Finally, 444 participants from QUH were divided into the training cohort (n = 310) and validation cohort (n = 134) based on the date of ultrasound examination. 81 participants from QMH were used to evaluate the external generalizability of our prediction models. A total of 1032 radiomic features of each ALN ultrasound image were extracted and used to establish the prediction models. The clinical model, radiomics model, and radiomics nomogram with clinical factors (RNWCF) were built. The performance of the models was assessed with respect to discrimination and clinical usefulness., Results: Although the radiomics model did not show better predictive efficacy than the clinical model, the RNWCF showed favorable predictive efficacy in the training cohort (AUC, 0.855; 95% CI 0.817-0.893), the validation cohort (AUC, 0.882; 95% CI 0.834-0.928), and the external test cohort (AUC, 0.858; 95% CI 0.782-0.921) compared with the clinical factor model and radiomics model., Conclusions: The RNWCF, a noninvasive, preoperative prediction tool that incorporates a combination of clinical and radiomics features, showed favorable predictive efficacy for the response of node-positive breast cancer to NAC. Therefore, the RNWCF could serve as a potential noninvasive approach to assist personalized treatment strategies, guide ALN management, avoiding unnecessary ALND., (© 2023. The Author(s).)

Objective: To examine the prognostic value of HRV measurements during anesthesia for postoperative clinical outcomes prediction using machine learning models., Data Sources: VitalDB, a comprehensive database of 6388 surgical patients admitted to Seoul National University Hospital., Eligibility Criteria for Study Selection: Cases with ECG lead II recording duration of less than one hour were excluded. Cases with more than 20% of missing HRV measurements were also excluded. A total of 5641 cases were eligible for the analyses., Methods: Six machine learning models including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Trees (GBT), Extreme Gradient Boosting (XGB), and an ensemble of the five baseline models were developed to predict postoperative clinical outcomes. The prediction models were trained using only clinical information, and using both clinical information and HRV features, respectively. Feature importance based on the SHAP method was used to assess the contribution of the HRV measurements to the outcome predictions. Subgroup analysis was also performed to evaluate the risk association between postoperative ICU stay and various HRV measurements such as heart rate, low-frequency power (LFP), and short-term fluctuation DFA [Formula: see text]., Result: The final cohort included 5641 unique cases, among whom 4678 (83.0%) cases had ages over 40, 2877 (51.0%) were male, 1073 (19.0%) stayed in ICU after surgery, 52 (0.9%) suffered in-hospital death, and 3167(56.1%) had a total length of hospital stay longer than 7 days. In the final test set, the highest AUROC performance with only clinical information was 0.79 for postoperative ICU stay, 0.58 for in-hospital mortality, and 0.76 for the total length of hospital stay prediction. Importantly, using both clinical information and HRV features, the AUROC performance was 0.83, 0.70, and 0.76 for the three clinical outcome predictions, respectively. Subgroup analysis found that patients with an average heart rate higher than 70, low-frequency power (LFP) < 33, and short-term fluctuation DFA [Formula: see text] < 0.95 during anesthesia, had a significantly higher risk of entering the ICU after surgery., Conclusion: This study suggested that HRV measurements during anesthesia are feasible and effective for predicting postoperative clinical outcomes., (© 2023. The Author(s).)

Parkinson's disease (PD) is mainly characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and neuroinflammation mediated by overactivated microglia and astrocytes. NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) has been reported to participate in various immune disorders, but its role in neurodegenerative diseases remains unclear. In the current study, we found that the expression of NLRC5 was increased in the nigrostriatal axis of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD, as well as in primary astrocytes, microglia and neurons exposed to different neurotoxic stimuli. In an acute MPTP-induced PD model, NLRC5 deficiency significantly reduced dopaminergic system degeneration and ameliorated motor deficits and striatal inflammation. Furthermore, we found that NLRC5 deficiency decreased the expression of the proinflammatory genes IL-1β, IL-6, TNF-α and COX2 in primary microglia and primary astrocytes treated with neuroinflammatory stimuli and reduced the inflammatory response in mixed glial cells in response to LPS treatment. Moreover, NLRC5 deficiency suppressed activation of the NF-κB and MAPK signaling pathways and enhanced the activation of AKT-GSK-3β and AMPK signaling in mixed glial cells. Furthermore, NLRC5 deficiency increased the survival of primary neurons treated with MPP + or conditioned medium from LPS-stimulated mixed glial cells and promoted activation of the NF-κB and AKT signaling pathways. Moreover, the mRNA expression of NLRC5 was decreased in the blood of PD patients compared to healthy subjects. Therefore, we suggest that NLRC5 promotes neuroinflammation and dopaminergic degeneration in PD and may serve as a marker of glial activation., (© 2023. The Author(s).)

Medical image processing has proven to be effective and feasible for assisting oncologists in diagnosing lung, thyroid, and other cancers, especially at early stage. However, there is no reliable method for the recognition, screening, classification, and detection of nodules, and even deep learning-based methods have limitations. In this study, we mainly explored the automatic pre-diagnosis of lung nodules with the aim of accurately identifying nodules in chest CT images, regardless of the benign and malignant nodules, and the insertion path planning of suspected malignant nodules, used for further diagnosis by robotic-based biopsy puncture. The overall process included lung parenchyma segmentation, classification and pre-diagnosis, 3-D reconstruction and path planning, and experimental verification. First, accurate lung parenchyma segmentation in chest CT images was achieved using digital image processing technologies, such as adaptive gray threshold, connected area labeling, and mathematical morphological boundary repair. Multi-feature weight assignment was then adopted to establish a multi-level classification criterion to complete the classification and pre-diagnosis of pulmonary nodules. Next, 3-D reconstruction of lung regions was performed using voxelization, and on its basis, a feasible local optimal insertion path with an insertion point could be found by avoiding sternums and/or key tissues in terms of the needle-inserting path. Finally, CT images of 900 patients from Lung Image Database Consortium and Image Database Resource Initiative were chosen to verify the validity of pulmonary nodule diagnosis. Our previously designed surgical robotic system and a custom thoracic model were used to validate the effectiveness of the insertion path. This work can not only assist doctors in completing the pre-diagnosis of pulmonary nodules but also provide a reference for clinical biopsy puncture of suspected malignant nodules considered by doctors., (© 2023. The Author(s).)

Background: Short-term and long-term comparative outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for multivessel coronary artery (MVCA) or left main coronary artery (LMCA) disease are highly debated., Goals: We performed a meta-analysis to evaluate the difference between PCI and CABG for the treatment of patients with MVCA or LMCA in long-term follow-up., Methods: Literatures were searched in PubMed, EMBASE and The Cochrane Library from January 1, 2000 to January 1, 2021, including RCTs and observational studies (OSs). The primary outcome was all-cause mortality at 10 years follow-up, and the secondary outcomes included cardiac mortality, repeated revascularization, myocardial infarction, and stroke., Results: A total of 5 RCTs reporting data from 3013 participants and 4 OSs of 5608 participants were included for analysis. There was no significant difference between PCI and CABG in all-cause mortality (Odds Ratio (OR) 1.03 [95% confidence interval (CI) 0.89 to 1.19]), whereas PCI was associated with higher cardiac mortality (OR 0.76 [95% CI 0.65 to 0.90]) and repeated revascularization rate comparing to CABG (OR 1.77 [95% CI 1.08 to 2.89]; I 2  = 94.61%). The difference between PCI and CABG in repeated revascularization in either RCTs or OSs, in myocardial infarction in either RCTs or OSs were not significant. In OSs, stroke rate in PCI group was lower than those in CABG, but not in RCTs. There was a significant increase of stroke rate in CABG comparing to PCI (OR 0.65 [95% CI 0.53 to 0.80]; I 2  = 0.00%). No significant difference between PCI and CABG in myocardial infarction was not observed (OR 0.92 [95% CI 0.64 to 1.31]; I 2  = 57.84%)., Conclusion: Evidence from our study and prior studies suggested the superiority of CABG over PCI in improving 5- but not 10-year survival among patients with MVCA. In the contrast, there was no significant difference between CABG and PCI for treating patients with LMCA in either 5- or 10-year survival rate. More long-term trials are needed to better define differences of outcome between 2 techniques., (© 2023. The Author(s).)

Background: Hepatocellular carcinoma is one of the most common and deadly cancers. The aim of this study was to elucidate the role of tRNA methyltransferase 6 (TRMT6) during HCC progression., Methods: The role of TRMT6 in the progression and prognosis of HCC was confirmed by analysis of online databases and clinical human samples. The effects of up-regulation or down-regulation of TRMT6 on HCC cell proliferation and PI3K/AKT pathway-related protein expressions were verified. The molecular mechanism was investigated in vivo by constructing subcutaneous xenograft tumor model., Results: TRMT6 was overexpressed in HCC tissues and associated with Tumour-Node-Metastasis (TNM) stage, primary tumor (T) and regional lymph node (N) classification. TRMT6 expressions in HCC cell lines were higher than that in normal liver cell. TRMT6 overexpression can promote HCC cell proliferation, increase the number of S phase cells. Interference with TRMT6 reduced the PI3K/AKT pathway-related protein expressions, and was reversed by the addition of IGF1. Interference with TRMT6 inhibited tumor growth in vivo and was related to PI3K/AKT pathway., Conclusions: Overexpression of TRMT6 promote HCC cell proliferation in vivo and in vitro through PI3K/AKT/mTOR axis, which provides a potential choice for the treatment of HCC in clinical practice., (© 2023. The Author(s).)

Background: Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear., Methods: In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings., Results: In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-β1 which activated the TGFβR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFβ signaling inhibitor SB431542 or knockdown of TGFβR1 could reverse the cisplatin resistance of ESCC cells. In 92 cases of human ESCC tissues, individuals with a high density of M2-TAMs had considerably higher levels of TGF-β1. These patients also had worse prognoses and richer stemness markers., Conclusion: TGF-β1 secreted from M2-TAMs promoted and maintained the stemness characteristic to induce cisplatin resistance in ESCC by activating the TGFβ1-Smad2/3 pathway., (© 2023. The Author(s).)

Background: WRKY transcription factors play key roles in plant development processes and stress response. Kandelia obovata is the most cold-resistant species of mangrove plants, which are the important contributors to coastal marine environment. However, there is little known about the WRKY genes in K. obovata., Results: In this study, a WRKY transcription factor gene, named KoWRKY40, was identified from mangrove plant K. obovata. The full-length cDNA of KoWRKY40 gene was 1420 nucleotide bases, which encoded 318 amino acids. The KoWRKY40 protein contained a typical WRKY domain and a C2H2 zinc-finger motif, which were common signatures to group II of WRKY family. The three-dimensional (3D) model of KoWRKY40 was formed by one α-helix and five β-strands. Evolutionary analysis revealed that KoWRKY40 has the closest homology with a WRKY protein from another mangrove plant Bruguiera gymnorhiza. The KoWRKY40 protein was verified to be exclusively located in nucleus of tobacco epidermis cells. Gene expression analysis demonstrated that KoWRKY40 was induced highly in the roots and leaves, but lowly in stems in K. obovata under cold stress. Overexpression of KoWRKY40 in Arabidopsis significantly enhanced the fresh weight, root length, and lateral root number of the transgenic lines under cold stress. KoWRKY40 transgenic Arabidopsis exhibited higher proline content, SOD, POD, and CAT activities, and lower MDA content, and H 2 O 2 content than wild-type Arabidopsis under cold stress condition. Cold stress affected the expression of genes related to proline biosynthesis, antioxidant system, and the ICE-CBF-COR signaling pathway, including AtP5CS1, AtPRODH1, AtMnSOD, AtPOD, AtCAT1, AtCBF1, AtCBF2, AtICE1, AtCOR47 in KoWRKY40 transgenic Arabidopsis plants., Conclusion: These results demonstrated that KoWRKY40 conferred cold tolerance in transgenic Arabidopsis by regulating plant growth, osmotic balance, the antioxidant system, and ICE-CBF-COR signaling pathway. The study indicates that KoWRKY40 is an important regulator involved in the cold stress response in plants., (© 2022. The Author(s).)

Background: To determine the optimal delivery time for women with diet-controlled gestational diabetes mellitus by comparing differences in adverse maternal-fetal outcome and cesarean section rates., Methods: This real-world retrospective study included 1,050 patients with diet-controlled gestational diabetes mellitus who delivered at 35-42 weeks' gestation. Data on patient characteristics, maternal-fetal outcomes, and cesarean section rate based on fetal gestational age were collected and analyzed. Differences between deliveries with and without iatrogenic intervention were also analyzed., Results: The cesarean section rate at ≥ 41 weeks' gestation was significantly higher than that at 39-39 + 6 weeks (56% vs. 39%, p = 0.031). There were no significant differences in multiple adverse maternal or neonatal outcomes at delivery before and after 39 weeks. Vaginal delivery rates were increased significantly at 39-39 + 6 weeks due to iatrogenic intervention (p = 0.005) and 40-40 + 6 weeks (p = 0.003) in patients without and with spontaneous uterine contractions, respectively., Conclusions: It's recommended that optimal delivery time for patients with diet-controlled gestational diabetes mellitus should be between 39- and 40 + 6 weeks' gestation. Patients who have Bishop scores higher than 4 can undergo iatrogenic intervention at 39-39 + 6 weeks. However iatrogenic interventions are not recommended for patients with low Bishop scores., (© 2022. The Author(s).)

Background: The plant architecture traits of maize determine the yield. Plant height, ear position, leaf angle above the primary ear and internode length above the primary ear together determine the canopy structure and photosynthetic efficiency of maize and at the same time affect lodging and disease resistance. A flat and tall plant architecture confers an obvious advantage in the yield of a single plant but is not conducive to dense planting and results in high rates of lodging; thus, it has been gradually eliminated in production. Although using plants that are too compact, short and density tolerant can increase the yield per unit area to a certain extent, the photosynthetic efficiency of such plants is low, ultimately limiting yield increases. Genetic mapping is an effective method for the improvement of plant architecture to identify candidate genes for regulating plant architecture traits., Results: To find the best balance between the yield per plant and the yield per unit area of maize, in this study, the F2:3 pedigree population and a RIL population with the same male parent were used to identify QTL for plant height (PH), ear height (EH), leaf angle and internode length above the primary ear (LAE and ILE) in Changchun and Gongzhuling for 5 consecutive years (2016-2020). A total of 11, 13, 23 and 13 QTL were identified for PH, EH, LAE, and ILE, respectively. A pleiotropic consistent QTL for PH overlapped with that for EH on chromosome 3, with a phenotypic variation explanation rate from 6.809% to 21.96%. In addition, there were major consistent QTL for LAE and ILE, and the maximum phenotypic contribution rates were 24.226% and 30.748%, respectively. Three candidate genes were mined from the three consistent QTL regions and were involved in the gibberellin-activated signal pathway, brassinolide signal transduction pathway and auxin-activated signal pathway, respectively. Analysis of the expression levels of the three genes showed that they were actively expressed during the jointing stage of vigorous maize growth., Conclusions: In this study, three consistent major QTL related to plant type traits were identified and three candidate genes were screened. These results lay a foundation for the cloning of related functional genes and marker-assisted breeding of related functional genes., (© 2022. The Author(s).)

Background: Mangroves plants, an important wetland system in the intertidal shores, play a vital role in estuarine ecosystems. However, there is a lack of a very effective method for extracting protein from mangrove plants for proteomic analysis. Here, we evaluated the efficiency of three different protein extraction methods for proteomic analysis of total proteins obtained from mangrove plant Kandelia obovata leaves., Results: The protein yield of the phenol-based (Phe-B) method (4.47 mg/g) was significantly higher than the yields of the traditional phenol (Phe) method (2.38 mg/g) and trichloroacetic acid-acetone (TCA-A) method (1.15 mg/g). The Phe-B method produced better two-dimensional electrophoresis (2-DE) protein patterns with high reproducibility regarding the number, abundance and coverage of protein spots. The 2-DE gels showed that 847, 650 and 213 unique protein spots were separated from the total K. obovata leaf proteins extracted by the Phe-B, Phe and TCA-A methods, respectively. Fourteen pairs of protein spots were randomly selected from 2-DE gels of Phe- and Phe-B- extracted proteins for identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) technique, and the results of three pairs were consistent. Further, oxygen evolving enhancer protein and elongation factor Tu could be observed in the 2-DE gels of Phe and Phe-B methods, but could only be detected in the results of the Phe-B methods, showing that Phe-B method might be the optimized choice for proteomic analysis., Conclusion: Our data provides an improved Phe-B method for protein extraction of K. obovata and other mangrove plant tissues which is rich in polysaccharides and polyphenols. This study might be expected to be used for proteomic analysis in other recalcitrant plants., (© 2021. The Author(s).)

Background: With the popularization of HRCT and VATS, the incidence of early stage lung cancer is increasing recent years. About 63% of small pulmonary nodules can not be accurately identified in VATS. We use 3-D reconstruction combined with dial positioning to analyze its accuracy and impact on patients undergoing VATS in our hospital., Method: All patients underwent HRCT scanning and 3-D reconstruction preoperatively to determine the scope of surgery. The precise positional relationship between the nodule and the nearest rib must be recorded. Locate the plane of pulmonary nodule on CT, rotate the plane to make the affected side upwards, take the highest point of pleura as 12 o'clock on the dial, record the corresponding point of the nodule meticulously, mark the pulmonary nodule on the skin of the patient. A 18G indwelling needle was used to puncture through the marker into the visceral pleura. Electrocautery mark was made on the bleeding point of the lung surface. Then wedge resection or segmental resection was made., Materials and Result: From September 2019 to December 2020, 74 patients underwent VATS pulmonary nodule resection in our institute, with an average age of (56.4 ± 11.7) years old. A total of 83 nodules were resected in 74 patients, 23 nodules received segmentectomy and 60 nodules received wedge resection with 16 benign nodules and 67 malignant nodules. The distance between the nodules and pleura was (0-25) mm, with an average of (8.0 ± 3.9) mm. The target nodules were found in all patients, the positioning accuracy was 97.6%. All patients were satisfied with the positioning method, and there was no scar left at the skin puncture point after operation., Conclusion: 3-D reconstruction combined with dial positioning method can reduce patients' anxiety preoperatively, avoid various complications, reduce hospitalization expenses, and has an acceptable accuracy and short learning curve, which can be further promoted and applied in clinic., (© 2021. The Author(s).)

Background: We used pericardioscope operation for a patient who suffered from subacute hemorrhagic pericarditis which usually have to had a sternotomy., Case Presentation: A pericardioscope was used in the operation rather than sternotomy on a 66-year-old male who was diagnosed with subacute hemorrhagic pericarditis after PCI(Percutaneous Coronary Intervention). He was discharged 7 days after the operation with an uneventfull postoperative course., Conclusions: We believe that this technique is a safe procedure without any major complications.

Background: Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study., Methods: A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured., Results: Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients., Conclusion: Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.

Background: Cryptic balanced translocations often evade detection by conventional cytogenetics. The preimplantation genetic testing (PGT) technique can be used to help carriers of balanced translocations give birth to healthy offspring; however, for carriers of cryptic balanced translocations, there is only one report about trying assisted reproduction using the PGT technique but with no pregnancy., Case Presentation: A couple had 3 births out of 4 pregnancies, and all died very young, with two of them having both cerebral palsy and glaucoma. The husband with oligoasthenospermia was found to be a cryptic balanced translocation carrier for t (9,13) (p24.3, q31.3) with G-banding, FISH (fluorescence in-situ hybridization), and MicroSeq techniques; live birth of a healthy baby girl was achieved with PGT/NGS (next-generation sequencing) for the couple., Conclusion: Here, we report for the first time a successful live birth of a healthy baby through the PGT technique for a family in which the husband is a carrier of the cryptic balanced translocation t (9,13) (p24.3, q31.3), presumably causative for cerebral palsy and glaucoma. Our study showed that the PGT/NGS technique can effectively help families with a cryptic balanced translocation have healthy offspring.

Introduction: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure., Materials and Methods: All 154 patients with COVID-19 were recruited from the Second People's Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study., Results: There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge., Conclusion: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.

Background: Low temperature is a major abiotic stress that seriously limits mangrove productivity and distribution. Kandelia obovata is the most cold-resistance specie in mangrove plants, but little is known about the molecular mechanism underlying its resistance to cold. Osmotin is a key protein associated with abiotic and biotic stress response in plants but no information about this gene in K. obovata was reported., Results: In this study, a cDNA sequence encoding osmotin, KoOsmotin (GenBank accession no. KP267758), was cloned from mangrove plant K. obovata. The KoOsmotin protein was composed of 221 amino acids and showed a calculated molecular mass of 24.11 kDa with pI 4.92. The KoOsmotin contained sixteen cysteine residues and an N-terminal signal peptide, which were common signatures to most osmotins and pathogenesis-related 5 proteins. The three-dimensional (3D) model of KoOsmotin, contained one α-helix and eleven β-strands, was formed by three characteristic domains. Database comparisons of the KoOsmotin showed the closest identity (55.75%) with the osmotin 34 from Theobroma cacao. The phylogenetic tree also revealed that the KoOsmotin was clustered in the branch of osmotin/OLP (osmotin-like protien). The KoOsmotin protein was proved to be localized to both the plasma membrane and cytoplasm by the subcellular localization analysis. Gene expression showed that the KoOsmotin was induced primarily and highly in the leaves of K. obovata, but less abundantly in stems and roots. The overexpressing of KoOsmotin conferred cold tolerance in Escherichia coli cells., Conclusion: As we known, this is the first study to explore the osmotin of K. obovata. Our study provided valuable clues for further exploring the function of KoOsmotin response to stress.

Background: Increases in the levels of serum C-reactive protein (CRP) and creatinine (Cr) and decreases in those of albumin (Alb) are commonly observed in acute pancreatitis (AP). We aimed to evaluate the efficacy of the Cr/Alb and CRP/Alb ratios in the prediction of surgical treatment effect in AP patients., Methods: This study retrospectively analyzed clinical data obtained from 140 AP patients who underwent debridement from January 2008 to November 2018 in Shanghai Ruijin Hospital. The Cr/Alb and CRP/Alb ratios at admission and before surgery were assessed in the analysis of clinical statistics, prediction of prognoses, and logistic regression analysis., Results: The admission Cr/Alb had the best predictive value of the four ratios. This value was significantly higher in patients with re-operation and those who died (P < 0.05) and was correlated with the Acute Physiology and Chronic Health Evaluation (APACHE II) score, admission CRP/Alb, preoperative Cr/Alb, and post-operative complications. The admission Cr/Alb could predict the risk of AP-related re-operation and mortality with sensitivities, specificities and areas under the curve of 86.3%, 61.7% and 0.824, and 73.4%, 81.3% and 0.794, respectively. At a cut-off value of 3.43, admission Cr/Alb values were indicative of a worse clinical state, including impaired laboratory test values, APACHE II scores, rates of post-operative complications and re-operation, and mortality (P < 0.05). In the logistic regression analysis, admission Cr/Alb values were independently related to the APACHE II score, post-operative renal failure, and mortality., Conclusion: Cr/Alb is a novel but promising, easy-to-measure, reproducible, non-invasive prognostic score for the prediction of the effect of debridement in AP patients.

Background: Accumulating evidence has highlighted the importance of microglial and astrocyte responses in the pathological development of postoperative cognitive dysfunction (POCD). However, the mechanisms involved are not well understood., Methods: A perioperative neurocognitive disorders (PND) mouse model was generated by administering etomidate, and cognitive function was assessed using the Morris water maze and novel object recognition tests. Excitatory and inhibitory postsynaptic currents were recorded to analyze neuronal activity. In addition, microglia and astrocytes were isolated by magnetic-activated cell sorting, and genes that were activated in these cells were identified using quantitative polymerase chain reaction., Results: We observed dramatic cognitive impairment at 1 and 3 weeks after etomidate was administered to 18 month-old mice. Microglia and astrocytes isolated from the hippocampus showed significant microglial activation during the early pathological stage (i.e., 1 week after etomidate injection) and an A1-specific astrocyte response during the late pathological stage (i.e., 3 weeks after etomidate injection). Furthermore, when microglia were eliminated before etomidate was injected, the A1-specific astrocyte activation response was significantly reduced, and cognitive function improved. However, when microglia were eliminated after etomidate application, astrocyte activation and cognitive function were not significantly altered. In addition, activating microglia immediately after a sedative dose of etomidate was injected markedly increased A1-specific astrocyte activation and cognitive dysfunction., Conclusions: A1-specific astrocyte activation is triggered by activated microglia during the initial pathological stage of PND and induces long-term synaptic inhibition and cognitive deficiencies. These results improve our understanding of how PND develops and may suggest therapeutic targets.

Background: Current therapies for multiple myeloma (MM) are associated with toxicity and resistance, highlighting the need for novel effective therapeutics. Berberine (BBR), a botanical alkaloid derived from several Berberis medicinal plants, has exhibited anti-tumor effects, including against multiple myeloma (MM); however, the molecular mechanism underlying the anti-MM effect has not been previously described. This study aimed to identify the target of berberine and related mechanisms involved in its therapeutic activity against MM., Results: Here, we demonstrated that BBR treatment killed MM cells in vitro and prolonged the survival of mice bearing MM xenografts in vivo. A screening approach integrating surface plasmon resonance (SPR) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified UHRF1 (ubiquitin-like with PHD and RING Finger domains 1) as a potential target of BBR. Combining molecular docking and SPR analysis, we confirmed UHRF1 as a BBR-binding protein and discovered that BBR binds UHRF1 in the tandem tudor domain and plant homeodomain (TTD-PHD domain). BBR treatment induced UHRF1 degradation via the ubiquitin-dependent proteasome system and reactivated p16 INK4A and p73 in MM cells. Overexpression of UHRF1 promoted the MM cell proliferation and rendered MM cells more resistant to BBR, while silencing of UHRF1 with siRNA attenuated BBR-induced cytotoxicity., Conclusions: In summary, our study has identified UHRF1 as a direct target of BBR and uncovered molecular mechanisms involved in the anti-MM activity of BBR. Targeting UHRF1 through BBR may be a novel therapeutic strategy against MM.

Background: Dehydration due to insufficient fluid intake (IFI) is detrimental to health. This cross-sectional study aimed to assess the fluid intake of urban adults in Wuxi, China, and to identify potential risk factors contributing to IFI., Methods: Adults were selected from the urban area of Wuxi, China, using a multiple-stage random sampling method. The fluid intake information was obtained with a 24-h self-reported diary over seven consecutive days in both summer and winter of 2015. A classification and regression tree (CART) analysis was conducted to detect the potential risk factors associated with IFI. CART is a machine-learning algorithm that portions the data into subsets by threshold., Results: A total of 584 adults aged 18-87 years were included. The results showed that the median (P25-P75) values of daily fluid intake of the participants were 1100 (800-1550) mL in summer and 1000 (750-1300) mL in winter. Women had a higher prevalence of IFI than men in both summer (odds ratio (OR) = 2.683, 95% confidence interval (CI): 1.830-3.934) and winter (OR = 2.636, 95% CI: 1.677-4.142). The results of CART analysis showed that, in summer, BMI < 25 kg/m 2 (probability: 64.2%) and age < 64 years (probability: 67.4%) were main risk factors of IFI for men, and BMI < 29 kg/m 2 (probability: 81.6%) and living in C Community (probability: 86.7%) were main risk factors for women. In winter, age < 40 years (probability: 81.8%) and BMI < 20 kg/m 2 (probability: 94.5%) were identified as main risk factors of IFI for men and women, respectively., Conclusions: Most of the participants living in the study site had IFI. The fluid consumption varied by gender, age, location, and BMI. The findings could be useful for the implementation and optimization of intervention programs by identifying the individuals who may at greater risk of dehydration.

Background: Ovarian cancer (OC) is the deadliest cause in the gynecological malignancies. Most OC patients are diagnosed in advanced stages with less than 40% of women cured. However, the possible mechanism underlying tumorigenesis and candidate biomarkers remain to be further elucidated., Results: Gene expression profiles of GSE18520, GSE54388, and GSE27651 were available from Gene Expression Omnibus (GEO) database with a total of 91 OC samples and 22 normal ovarian (OV) tissues. Three hundred forty-nine differentially expressed genes (DEGs) were screened between OC tissues and OV tissues via GEO2R and online Venn software, followed by KEGG pathway and gene ontology (GO) enrichment analysis. The enriched functions and pathways of these DEGs contain male gonad development, cellular response to transforming growth factor beta stimulus, positive regulation of transcription from RNA polymerase II promoter, calcium independent cell-cell adhesion via plasma membrane cell adhesion molecules, extracellular matrix organization, pathways in cancer, cell cycle, cell adhesion molecules, PI3K-AKT signaling pathway, and progesterone mediated oocyte maturation. The protein-protein network (PPI) was established and module analysis was carried out using STRING and Cytoscape. Next, with PPI network analyzed by four topological methods in Cytohubba plugin of Cytoscape, 6 overlapping genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) were eventually selected. GEPIA and Oncomine were implemented for validating the gene expression and all the six hub genes were highly expressed in OC specimens compared to normal OV tissues. Furthermore, 5 of 6 genes except for DTL were associated with worse prognosis using Kaplan Meier-plotter online tool and 3 of 6 genes were significantly related to clinical stages, including RRM2, DTL, and KIF15. Additionally, cBioPortal showed that TOP2A and RRM2 were the targets of cancer drugs in patients with OC, indicating the other four genes may also be potential drug targets., Conclusion: Six hub genes (DTL, DLGAP5, KIF15, NUSAP1, RRM2, and TOP2A) present promising predictive value for the development and prognosis of OC and may be used as candidate targets for diagnosis and treatment of OC.

Background: To investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients., Methods: We retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression., Results: Post-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006)., Conclusion: Cervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.

Background: Pierre Robin Sequence (PRS) patients are known for their triad of micrognathia, glossoptosis, and airway obstruction. Their airway can be a challenge even for the most experienced pediatric anesthesiologist., Case Presentation: We report the case of a 9 day old 3.5 kg boy diagnosed with PRS, cleft palate, and a vallecular cyst with severe upper airway obstruction. The combination of PRS, cleft palate and the presence of vallecular cyst made this a cascade reaction of difficult airway. Due to his unique anatomy, we didn't appreciate how difficult his airway was until multiple attempts with high-tech equipment failed. Ultimately it was the finger guide intubation, this old technique without any equipment, that rescued this patient from lose of airway., Conclusions: The boy was successfully rescued by finger guided intubation. Finger guide intubation should be added to the anesthesiologist's newborn rescue intubation training.

Background: The efficacy and safety of multikinase inhibitor anlotinib have been confirmed in the treatment of advanced non-small cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by anlotinib were not fully elucidated, and the underlying mechanisms related to resistance remain largely elusive., Methods: Cell viability, colony formation, apoptosis and tumor growth assays were performed to examine the effect of anlotinib on lung cancer cells in vitro and in vivo. The punctate patterns of LC3-I/II were detected by confocal microscopy. HUVECs motility was detected using Transwell and scratch wound-healing assay. To visualize the microvessels, tubular formation assay was performed. The expression of LC3-I/II and beclin-1 and the changes of JAK2/STAT3/VEGFA pathway were detected by western blotting. The VEGFA levels in tumor supernatant were measured by ELISA., Results: Anlotinib treatment decreased cell viability and induced apoptosis in Calu-1 and A549 cells. Moreover, anlotinib induced human lung cancer cell autophagy in a dose- and time-dependent manner. Blocking autophagy enhanced the cytotoxicity and anti-angiogenic ability of anlotinib as evidenced by HUVECs migration, invasion, and tubular formation assay. Co-administration of anlotinib and chloroquine (CQ) further reduced VEGFA level in the tumor supernatant, compared with that of anlotinib or CQ treatment alone. When autophagy was induced by rapamycin, the JAK2/STAT3 pathway was activated and VEGFA was elevated, which was attenuated after deactivating STAT3 by S3I-201. Further in vivo studies showed that anlotinib inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3/VEGFA pathway, and CQ enhanced this effect., Conclusion: Anlotinib induced apoptosis and protective autophagy in human lung cancer cell lines. Autophagy inhibition further enhanced the cytotoxic effects of anlotinib, and potentiated the anti-angiogenic property of anlotinib through JAK2/STAT3/VEGFA signaling.

Background: The impact of evidence-based medicine (EBM) training techniques in primary healthcare professionals remains to be determined., Methods: A non-randomized controlled trial (NRCT) was performed aiming to assess the two methods of evidence-based medicine training for primary healthcare professionals by assessing evidence based practice (EBP) related knowledge (EBP-K), attitude (EBP-A), personal application (EBP-P), anticipated future use (EBP-F), and community management of hypertension. Participants were recruited and assigned to either an EBM training group that receiving a weekly face-to-face EBM training course, or an EBM self-instruction course for eight weeks. A validated instrument was applied to evaluate the four aspects of EBP. Additionally, community management of hypertension was assessed by comparing the the rate of detection, blood pressure control, standard management, grading management and patient satisfaction between 2015 and 2016 to measure training efficacy. The difference between the impact of these two interventions was assessed statistically., Results: One hundred fifty-one participants (69 in the face-to-face EBM training group and 82 in the self-instruction group) were included. Compared to self-instruction, the face-to-face EBM training was associated with significantly improved EBP-Knowledge (26.14 ± 4.22 vs. 22.44 ± 4.47, P < 0.05), EBP-Personal application (22.52 ± 6.18 vs. 16.89 ± 5.99, P < 0.05), and EBP-Future use (44.04 ± 8.97 vs. 37.71 ± 8.39, P < 0.05). EBP-Attitude scores (10.89 ± 4.52 vs.14.93 ± 5.92, P < 0.000) were lower in the EBM training group. Stratified analyses showed that the results were consistent regardless of the participants' gender, professional role (doctors & apothecaries or nurses), rank (junior or senior doctors & apothecaries), or specialty (Traditional Chinese or Western Medicine). Assessment of community hypertension management revealed that the rate of blood pressure control, standardized hypertension management and patient satisfaction was significantly better in group A than group B (1.14% vs.0.69, 2.85% vs.1.68 and 2.41% vs.0.84%)., Conclusions: A face-to-face EBM training course improved primary healthcare professionals' EBP knowledge, attitudes, personal application, and anticipated future use. Effective EBM training may improve the efficacy of primary health care services., Trial Registration: Non-Randomized Controlled Trial ChiCTR1800017498 , August 1, 2018.

Background: Spinal tuberculosis is a frequent cause of psoas abscess (PA), and PA largely negates the efficacy of antituberculosis therapy. This study aimed to investigate the clinical outcome of preoperative percutaneous catheter drainage (PCD) in patients with lumbar spinal tuberculosis and PA., Methods: Between January 2015 and January 2017, 72 patients with lumbar spinal tuberculosis with PA were assigned to group A (preoperative PCD) and group B (n = 36 per group). All patients received posterior pedicle screw fixation and anterior focal debridement and fusion. Data on intraoperative blood loss, the duration of the surgery, and the length of the anterior incision were recorded, as well as the postoperative anal exhaust time, visual analogue scale (VAS), Cobb angle, lumbar vertebra function, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and sinus tract formation., Results: Sixty-eight patients were followed up for an average time of 13 months (range 6-21 months). Until the final follow-up, no mixed infections, recurrence of tuberculosis, pedicle screw loosening, or screw pullout had occurred. There were significant between-group differences in blood loss, surgery duration, anterior incisional length, postoperative anal exhaust time, and sinus tract formation. As compared with group B, the ESR and CRP levels of the patients in group A were markedly improved following 3 weeks of antituberculosis therapy and 1 week postsurgery., Conclusion: Preoperative PCD helps to increase the efficacy of antituberculosis therapy prior to surgery, reduce surgical trauma, and avoid postoperative complications, making it a safe and feasible treatment option for lumbar spinal tuberculosis with PA.

Background: To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) in the management of adrenal gland metastases (AGMs) from lung cancer. Moreover, it is the first two-institutional experience and the largest-to-date study to report the safety and efficacy of SBRT for inoperable AGM from lung cancer., Methods: In this retrospective study, 30 patients (27 males, 3 females) with 32 AGMs were treated by SBRT from October 2006 to June 2016. Of these, 11 patients were treated with the intent of controlling all known metastatic sites and 19 for palliation of bulky AGMs. Follow-up was performed every 3 months for evaluations of efficacy and safety. Factors predictive of overall survival (OS) and local control (LC) were identified with univariate and then multivariate analysis., Results: Median follow-up time was 10.7 months (2.9-96.4 months). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 23.3%, 33.3%, 33.3% and 16.7% respectively. The 6-month, 1, and 2-year LC rates were 96.9%, 96.9%, and 72.7% respectively. Additionally, the 6-month, 1, and 2-year OS rates were 85.6%, 58.1%, and 54.0% respectively while 6-month, 1, and 2-year progression free survival (PFS) rates were 39.5%, 24.6%, and 8.2%, respectively. All the patients with cancer-induced pain (8 with abdominal pain and 6 with lumbar back pain) had significant alleviations after SBRT. The treatment was well tolerated with only 1 patient reporting grade-3 diarrhoea. No predictors of OS and LC were found after multivariate analysis, while it was demonstrated that biologic equivalent dose (BED 10 , α/β = 10) ≥85.5Gy (P = 0.007) and gross tumor volume < 30 ml (P = 0.003) correlated with LC only after univariate analysis., Conclusion: SBRT is a safe and effective treatment modality in the management of AGMs from lung cancer with high LC rates and acceptable toxicity.

Background: Gastrointestinal symptoms occur in approximately 50% of patients with systemic lupus erythematous with low specificity. Although it is well established that colon cancer is one of the many gastrointestinal manifestations associated with systemic lupus erythematous, the diagnosis and treatment remains complex due to adrenal insufficiency symptoms., Case Presentation: A 43-year-old Chinese woman with a five-year history of systemic lupus erythematous was diagnosed with colon cancer based on imaging test. A radical bowel resection was performed successfully. To avoid serious complications during surgery, prednisone was replaced with methylprednisolone therefore avoiding adrenal insufficiency. The patient was subsequently treated with mFOLFOX6 chemotherapy and recovered well., Conclusion: There is a lack of reports for treatment of colon cancer in patients with systemic lupus erythematous. This report provides an effective way to diagnose colon cancer in patients with systemic lupus erythematous and illustrates a successful therapy strategy for this complex medical condition.

Background: Cryptosporidium spp. are important diarrhea-causing pathogens in humans and animals. Comparative genomic analysis indicated that Cryptosporidium-specific MEDLE family proteins may contribute to host adaptation of Cryptosporidium spp., and a recent study of one member of this family, CpMEDLE-2 encoded by cgd5&#95;4590, has provided evidence supporting this hypothesis. In this study, another member of the protein family, CpMEDLE-1 of Cryptosporidium parvum encoded by cgd5&#95;4580, which is distinct from CpMEDLE-2 and has no signature motif MEDLE, was cloned, expressed and characterized to understand its function., Methods: CpMEDLE-1 was expressed in Escherichia coli and polyclonal antibodies against the recombinant CpMEDLE-1 protein were prepared in rabbits. Quantitative PCR was used to analyze the expression profile of cgd5&#95;4580 in C. parvum culture. Immunofluorescence staining was used to locate CpMEDLE-1 expression in life-cycle stages, and in vitro neutralization assay with antibodies was adopted to assess the role of the protein in C. parvum invasion., Results: The results indicated that cgd5&#95;4580 had a peak expression at 2 h of C. parvum culture. CpMEDLE-1 was located in the mid-anterior region of sporozoites, probably within the dense granules. The neutralization efficiency of anti-CpMEDLE-1 antibodies was approximately 40%., Conclusions: The differences in protein and gene expression profiles between CpMEDLE-1 and CpMEDLE-2 suggest that MEDLE proteins have different subcellular locations, are developmentally regulated, could be potentially involved in the transcriptional regulation of the expression of parasite or host proteins and may exert their functions in different stages of the invasion and development process.

Background: Mivacurium is the shortest acting nondepolarizing muscle relaxant currently available; however, the effect of different dosages and injection times of intravenous mivacurium administration in children of different ages has rarely been reported. This study was aimed to evaluate the muscle relaxant effects and safety of different mivacurium dosages administered over different injection times in pediatric patients., Methods: Six hundred forty cases of pediatric patients, aged 2 m-14 years, ASA I or II, were divided into four groups (Groups A, B, C, D) according to the age class (2-12 m, 13-35 m, 3-6 years and 7-14 years) respectively, also each group were divided into four subgroups by induction dose (0.15, 0.2 mg/kg in 2-12 m age class; 0.2, 0.25 mg/kg in other three age classes), and mivacurium injection time (20 s, 40 s), totally 16 subgroups. Neuromuscular transmission was monitored with supramaximal train-of-four stimulation of the ulnar nerve. Radial artery blood (1 ml) was sampled to quantify plasma histamine concentrations before and 1, 4, and 7 min after mivacurium injection (P0, P1, P2 and P3)., Results: Five hundred sixty-two cases completed the study. There were no demographic differences within the four groups. The onset time of 0.2 mg/kg groups in 2-12 m aged patients were shorter than those of 0.15 mg/kg groups (189 ± 64 s vs. 220 ± 73 s, 181 ± 60 s vs. 213 ± 71 s, P <0.05), and the recovery times were no statistical differences. The T1 25% recovery time of 0.2 mg/kg in 3-6 years aged patients was shorter than that of 0.25 mg/kg group (693 ± 188 s vs. 800 ± 206 s, P <0.05). The onset and recovery times of mivacurium were not different in 13-35 m and 7-14 years aged patients. The plasma concentrations of histamine at P0, P1, P2 and P3 were not different within four groups., Conclusions: The induction dose and injection time of mivacurium had mostly insignificant effects on onset and recovery times. The main exception to this was that in 2-12 m aged patients, increasing the dose of mivacurium from 0.15 to 0.2 mg/kg accelerated the onset time by about 30 s. Mivacurium produced no significant release of histamine in any age group at the doses studied., Trial Registration: ClinicalTrials.gov Identifier- NCT02117401 , July 14, 2014. (Retrospectively registered).

Background: The actin cytoskeleton-associated protein palladin plays an important role in cell motility, morphogenesis and adhesion. In mice, Palladin deficient embryos are lethal before embryonic day (E) 15.5, and exhibit severe cranial neural tube and body wall closure defects. However, the mechanism how palladin regulates the process of cranial neural tube closure (NTC) remains unknown., Methods: In this paper, we use gene knockout mouse to elucidate the function of palladin in the regulation of NTC process., Results: We initially focuse on the expression pattern of palladin and found that in embryonic brain, palladin is predominantly expressed in the neural folds at E9.5. We further check the major cellular events in the neural epithelium that may contribute to NTC during the early embryogenesis. Palladin deficiency leads to a disturbance of cytoskeleton in the neural tube and the cultured neural progenitors. Furthermore, increased cell proliferation, decreased cell differentiation and diminished apical cell apoptosis of neural epithelium are found in palladin deficient embryos. Cell cycle of neural progenitors in Palladin -/- embryos is much shorter than that in wt ones. Cell adhesion shows a reduction in Palladin -/- neural tubes., Conclusions: Palladin is expressed with proper spatio-temporal pattern in the neural folds. It plays a crucial role in regulating mouse cranial NTC by modulating cytoskeleton, proliferation, differentiation, apoptosis, and adhesion of neural epithelium. Our findings facilitate further study of the function of palladin and the underlying molecular mechanism involved in NTC.

Background: Cross breeding is the most commonly used method in chrysanthemum (Chrysanthemum morifolium) breeding; however, cross barriers always exist in these combinations. Many studies have shown that paternal chromosome doubling can often overcome hybridization barriers during cross breeding, although the underlying mechanism has seldom been investigated., Results: In this study, we performed two crosses: C. morifolium (pollen receptor) × diploid C. nankingense (pollen donor) and C. morifolium × tetraploid C. nankingense. Seeds were obtained only from the latter cross. RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ) were used to investigate differentially expressed genes and proteins during key embryo development stages in the latter cross. A previously performed cross, C. morifolium × diploid C. nankingense, was compared to our results and revealed that transcription factors (i.e., the agamous-like MADS-box protein AGL80 and the leucine-rich repeat receptor protein kinase EXS), hormone-responsive genes (auxin-binding protein 1), genes and proteins related to metabolism (ATP-citrate synthase, citrate synthase and malate dehydrogenase) and other genes reported to contribute to embryo development (i.e., LEA, elongation factor and tubulin) had higher expression levels in the C. morifolium × tetraploid C. nankingense cross. In contrast, genes related to senescence and cell death were down-regulated in the C. morifolium × tetraploid C. nankingense cross., Conclusions: The data resources helped elucidate the gene and protein expression profiles and identify functional genes during different development stages. When the chromosomes from the male parent are doubled, the genes contributing to normal embryo developmentare more abundant. However, genes with negative functions were suppressed, suggesting that chromosome doubling may epigenetically inhibit the expression of these genes and allow the embryo to develop normally.

Background: Aiweixin (AWX) is a traditional Uyghur medicine prescription, and has been mainly used to treat heart and brain diseases for a long time. Previous studies indicated that AWX had therapeutic effects in a rat model of myocardial ischemia reperfusion injury. In this study, we investigate whether AWX has protective effects against chromium toxicity in Caenorhabditis elegans (C. elegans)., Methods: The AWX decoction was the conventional product for clinical use. It was added into M9 buffer in a certain volume for the treatment to the wild-type C. elegans and mutational worms, daf-16, glp-1(notch), daf-2, rsks-1 and eat-2. Assays for hexavalent chromium {Cr(VI)} stress and reactive oxygen species (ROS) production were used., Results: We found that AWX at moderate contents (0.083, 0.1, 0.125 volume of AWX/total volume) increased resistance of C. elegans to Cr(VI) exposure, although higher contents of AWX are toxic for C. elegans. The protective effect of AWX was DAF-16-dependent, but independent on the DAF-2, GLP-1, RSKS-1 and EAT-2. AWX (0.1 volume of AWX/total volume) significantly reduced ROS production of C. elegans induced by Cr(VI) exposure., Conclusion: These results indicated the AWX protected against the toxicity of Cr(VI) in C. elegans, and the oxidative stress protective mechanism in worms should be involved.

Background: Growth hormone secretagogue receptor (GHSR) and its ligand, ghrelin, are important modulators in weight control and energy homeostasis. Recently, ghrelin is also involved in experimental colitis, but the role of GHSR in the development of colitis is unclear. The aim was to examine the underlying mechanism of GHSR in IBD development., Methods: The temporal expression of GHSR/ghrelin was determined in dextran sulphate sodium (DSS) induced colitis in Wt mice. The severity of DSS induced colitis from GHSR(-/-) and WT mice was compared at clinical/pathological levels. Furthermore, the function of macrophages was evaluated in vivo and in vitro., Results: Lack of GHSR attenuated colitis significantly at the clinical and pathological levels with reduced colonic pro-inflammatory cytokines (P < 0.05). This is consistent with the observation of less colonic macrophage infiltration and TLRs expression from DSS-treated GHSR(-/-) mice compared to WT mice (P < 0.05). Furthermore, there was significantly reduced pro-inflammatory cytokines in LPS-stimulated macrophages in vitro from GHSR(-/-) mice than WT mice (P < 0.05). Moreover, D-lys(3)-GHRP6 (a GHSR antagonist) reduced LPS-induced macrophage pro-inflammatory cytokines from WT mice in vitro., Conclusions: GHSR contributes to development of acute DSS-induced colitis, likely via elevated pro-inflammatory cytokines and activation of macrophages. These data suggest GHSR as a potential therapeutic target for IBD.

Background: Vitamin C (VitC) has recently been shown to exert beneficial effects, including protecting organ function and inhibiting inflammation, in various critical care conditions, but the specific mechanism remains unclear. Induction of heme oxygenase (HO)-1, a heat shock protein, has been shown to prevent organ injuries in hemorrhagic shock (HS) but the relationship between VitC and HO-1 are still ill-defined so far. Here we conducted a systemic in vivo study to investigate if VitC promoted HO-1 expression in multiple organs, and then tested if the HO-1 induction property of VitC was related to its organ protection and anti-inflammatory effect., Methods: Firstly, to determine the HO-1 induction property of VitC, the HO-1 level were measured in tissues including kidney, liver and lung of the normal and HS model of Sprague-Dawley (SD) rats after VitC treatment (100 mg/kg body weight). Secondly, to testify if VitC prevented HS related organ injuries via inducing HO-1, the HS model of rats were separately pre- and post-treated with VitC, and some of them also received Zinc protoporphyrin (Znpp), a specific HO-1 inhibitor. The HO-1 activity in tissues was tested; the organ injuries (as judged by histological changes in tissues and the biochemical indicators level in serum) and inflammatory response in tissues (as judged by the level of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-6 ) were analyzed., Results: The HO-1 mRNA and protein level in kidney, liver, and lung were highly induced by VitC treatement under normal and HS conditions. The HO-1 activity in tissues was enhanced by both VitC pre- and post-treatment, which was shown to improve the organ injuries and inhibit the inflammatory response in the HS model of rats. Of note, the beneficial effects of VitC were abolished after HO-1 activity was blocked by Znpp., Conclusions: VitC led to a profound induction of HO-1 in multiple organs including the kidney, liver and lung, and this property might be responsible for the organ protection and inflammation inhibitory effects of both pre- and post-treatment with VitC in HS.