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Xiao Yu Hou,1 Chun Rong Peng,2 Guo Nan Zhang,2 Deng Feng Wang2 1School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Gynecologic Oncology, Sichuan Cancer Hospital & Institute, The Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaCorrespondence: Deng Feng Wang, Department of Gynecologic Oncology, Sichuan Cancer Hospital & Institute, The Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, People’s Republic of China, Tel +86 15982222707, Fax +86 28 85420116, Email wonderful_96@163.comIntroduction: Cervical cancer is the fourth most common malignancy in women worldwide, and sinonasal inverted papilloma (SIP) is a rare benign sinus tumor with characteristics including a destructive growth pattern, high recurrence rate, and common malignant transformation. Cervical squamous cell carcinoma (SCC) combined with SIP has not been reported thus far.Case Presentation: A 55-year-old woman was diagnosed with cervical SCC in our center and treated with concurrent radiochemotherapy. During the follow-up period after the completion of cervical cancer treatment, the progression of cervical squamous cell carcinoma was first considered because the squamous cell carcinoma antigen (SCCA) levels remained high and slowly increased. However, SIP was found after a detailed investigation. The SCCA levels returned to normal after surgery. Two months after the surgery, because SCCA slowly increased again, it was found that the SIP recurred. After additional surgical treatment, the SCCA level returned to normal.Discussion and Conclusion: First, SCCA is an important indicator for monitoring changes in cervical SCC. When the changes in SCCA levels are inconsistent with the prognosis of cervical SCC, we should be vigilant about considering the possibility of other diseases existing at other sites in the body, which might lead to the earlier detection and treatment of SIP. Second, We recommended that SCCA be used as a routine monitoring index for SIP. If available, SCCA1 and SCCA2 should be evaluated to provide a more detailed assessment. Finally, for a high recurrence rate of SIP, anti-HPV treatment might be considered to reduce the risk of recurrence.Keywords: cervical squamous cell carcinoma, inverted papilloma, squamous cell carcinoma antigen, human papilloma virus

Previous studies revealed extensive genetic introgression between Ovis species, which affects genetic adaptation and morphological traits. However, the exact evolutionary scenarios underlying the hybridization between sheep and allopatric wild relatives remain unknown. To address this problem, we here integrate the reference genomes of several ovine and caprine species: domestic sheep, argali, bighorn sheep, snow sheep, and domestic goats. Additionally, we use 856 whole genomes representing 169 domestic sheep populations and their six wild relatives: Asiatic mouflon, urial, argali, snow sheep, thinhorn sheep, and bighorn sheep. We implement a comprehensive set of analyses to test introgression among these species. We infer that the argali lineage originated ∼3.08 to 3.35 Mya and hybridized with the ancestor of Pachyceriforms (e.g. bighorn sheep and snow sheep) at ∼1.56 Mya. Previous studies showed apparent introgression from North American Pachyceriforms into the Bashibai sheep, a Chinese native sheep breed, despite of their wide geographic separation. We show here that, in fact, the apparent introgression from the Pachyceriforms into Bashibai can be explained by the old introgression from Pachyceriforms into argali and subsequent recent introgression from argali into Bashibai. Our results illustrate the challenges of estimating complex introgression histories and provide an example of how indirect and direct introgression can be distinguished., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Midazolam is a short-acting benzodiazepine frequently used in the perioperative setting. This study aimed to investigate the potential impact of intraoperative midazolam on postoperative delirium (POD) in older patients undergoing non-cardiac surgery., Methods: This study included patients aged ≥ 65 years who received general anaesthesia between April 2020 and April 2022 in multiple hospitals across China. POD occurring within 7 days was assessed using the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM). Univariable and multivariable logistic regression models based on the random effects were used to determine the association between midazolam administration and the occurrence of POD, presented as risk ratio (RR) and 95% confidence intervals (CI). Kaplan-Meier cumulative incidence curve was plotted to compare the distribution of time to POD onset between patients who received midazolam and those who did not. Subgroup analyses based on specific populations were performed to explore the relationship between midazolam and POD., Results: In all, 5,663 patients were included, of whom 723 (12.8%) developed POD. Univariate and multivariable logistic regression analyses based on random effects of different hospitals showed no significant association between midazolam medication and POD among older population (unadjusted RR=0.96, 95% CI: 0.90-1.30, P=0.38; adjusted RR=1.09, 95% CI: 0.91-1.33, P=0.35). Kaplan-Meier curve showed no difference in the distribution of time to POD onset (Hazard ratio [HR]=1.02, 95%CI: 0.88-1.18, P=0.82). The results of subgroup analyses found that intraoperative midazolam treatment was not associated with POD in the specific subgroups of patients., Conclusions: Intraoperative administration of midazolam may not be associated with an increased risk of POD in older patients undergoing non-cardiac surgery., Competing Interests: Conflicts of Interest: The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

Objective: To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22)., Design: A prospective cross-sectional study., Setting: The rhinology ward at our institution, a tertiary hospital., Participants: Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires., Main Outcome Measures: Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22., Results: Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists., Conclusion: Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30., (© 2024 John Wiley & Sons Ltd.)

Competing Interests: There are no conflicts of interest.

How to cite this article: Cong N, Wang D, Xue F. Nocturnal Infusion of Low-dose Dexmedetomidine and Propofol for Prevention of Delirium Occurring in the ICU after Hip Fracture Surgery in Elderly Patients. Indian J Crit Care Med 2024;28(9):894-895., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

Purpose: Radiation-induced intestinal injury (RIII) commonly occur during abdominal-pelvic cancer radiation therapy; however, no effective prophylactic or therapeutic agents are available to manage RIII currently. This study aimed to clarify the potential of probiotic consortium supplementation in alleviating RIII., Methods and Materials: Male C57BL/6J mice were orally administered a probiotic mixture comprising Bifidobacterium longum BL21, Lactobacillus paracasei LC86, and Lactobacillus plantarum Lp90 for 30 days before exposure to 13 Gy of whole abdominal irradiation. The survival rates, clinical scores, and histologic changes in the intestines of mice were assessed. The impacts of probiotic consortium treatment on intestinal stem cell proliferation, differentiation, and epithelial barrier function; oxidative stress; and inflammatory cytokines were evaluated. A comprehensive examination of the gut microbiota composition was conducted through 16S rRNA sequencing, while changes in metabolites were identified using liquid chromatography-mass spectrometry., Results: The probiotic consortium alleviated RIII, as reflected by increased survival rates, improved clinical scores, and mitigated mucosal injury. The probiotic consortium treatment exhibited enhanced therapeutic effects at the histologic level compared with individual probiotic strains, although there was no corresponding improvement in survival rates and colon length. Moreover, the probiotic consortium stimulated intestinal stem cell proliferation and differentiation, enhanced the integrity of the intestinal epithelial barrier, and regulated redox imbalance and inflammatory responses in irradiated mice. Notably, the treatment induced a restructuring of the gut microbiota composition, particularly enriching short-chain fatty acid-producing bacteria. Metabolomic analysis revealed distinctive metabolic changes associated with the probiotic consortium, including elevated levels of anti-inflammatory and antiradiation metabolites., Conclusions: The probiotic consortium attenuated RIII by modulating the gut microbiota and metabolites, improving inflammatory symptoms, and regulating oxidative stress. These findings provide new insights into the maintenance of intestinal health with probiotic consortium supplementation and will facilitate the development of probiotic-based therapeutic strategies for RIII in clinical practice., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Peptide-based frameworks aim to integrate protein architecture into solid-state materials using simpler building blocks. Despite the growing number of peptide frameworks, there are few strategies to rationally engineer essential properties like pore size and shape. Designing peptide assemblies is generally hindered by the difficulty of predicting complex networks of weak intermolecular interactions. Peptides conjugated to polyaromatic groups are a unique case where assembly appears to be strongly driven by π-π interactions, suggesting that rationally adjusting the geometry of the π-stackers could create novel structures. Here, we report peptide elongation as a simple mechanism to predictably tune the angle between the π-stacking groups to produce a remarkable diversity of pore shapes and sizes, including some that are mesoporous. Notably, rapid jumps in pore size and shape can occur with just a single amino acid insertion. The geometry of the π-stacking residues also significantly influences framework structure, representing an additional dimension for tuning. Lastly, sequence identity can also indirectly modulate the π-π interactions. By correlating each of these factors with detailed crystallographic data, we find that, despite the complexity of peptide structure, the shape and polarity of the tectons are straightforward predictors of framework structure. These guidelines are expected to accelerate the development of advanced porous materials with protein-like capabilities.

Background: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. Enhanced recovery after surgery (ERAS) can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains., Materials and Methods: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes, and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay after surgery., Results: A total of 245 patients (age of 79.8±3.4 year) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between nonfrail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery., Conclusion: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution., Results: We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B, BMPR2, RALYL, COL21A1, and LRP1B) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B, with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats., Conclusions: Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock., (© 2024. The Author(s).)

Background: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear., Methods: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to quantify inflammatory factors (IL-1β, IL-6, TNF-α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α-SMA, TGF-β1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining., Results: In vivo, CVB3-AMG487 reduced cardiac injury, α-SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL-1β, IL-6, and TNF-α). In vitro, CXCL4/CXCR3B axis activation TGF-β1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation., Conclusion: CXCL4 acts as a profibrotic factor in TGF-β1/Smad2/3 pathway-induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objective: Surgical treatment with internal fixation, specifically percutaneous fixation with three cannulated compression screws (CCSs), is the preferred choice for young and middle-aged patients. The mechanical advantage of the optimal spatial configuration with three screws provides maximum dispersion and cortical support. We suspect that the spatial proportion of the oblique triangle configuration (OTC) in the cross-section of the femoral neck isthmus (FNI) may significantly improve shear and fatigue resistance of the fixed structure, thereby stabilizing the internal fixation system in femoral neck fracture (FNF). This study aims to explore the mechanical features of OTC and provide a mechanical basis for its clinical application., Methods: Twenty Sawbone femurs were prepared as Pauwels type III FNF models and divided equally into two fixation groups: OTC and inverted equilateral triangle configuration (IETC). Three 7.3 mm diameter cannulated compression screws (CCSs) were used for fixation. The specimens of FNF after screw internal fixation were subjected to static loading and cyclic loading tests, respectively, with five specimens for each test. Axial stiffness, 5 mm failure load, ultimate load, shear displacement, and frontal rotational angle of two fragments were evaluated. In the cyclic loading test, the load sizes were 700 N, 1400 N, and 2100 N, respectively, and the fracture end displacement was recorded. Results were presented as means ± SD. Data with normal distributions were compared by the Student's t test., Results: In the static loading test, the axial stiffness, ultimate load, shear displacement, and frontal rotational angle of two fragments were (738.64 vs. 620.74) N/mm, (2957.61 vs. 2643.06) N, (4.67 vs. 5.39) mm, and (4.01 vs. 5.52)° (p < 0.05), respectively. Comparison between the femoral head displacement after 10,000 cycles of 700N cyclic loading and total displacement after 20,000 cycles of 700-1400N cyclic loading showed the OTC group was less than the IETC group (p < 0.05). A comparison of femoral head displacement after 10,000 cycles of 1400N and 2100N cycles and total displacement after 30,000 cycles of 700-2100N cycles showed the OTC group was less than another group, but the difference was not significant (p > 0.05)., Conclusion: When three CCSs are inserted in parallel to fix FNF, the OTC of three screws has obvious biomechanical advantages, especially in shear resistance and early postoperative weight-bearing, which provides a mechanical basis for clinical selection of ideal spatial configuration for unstable FNF., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined., Methods: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism., Results: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment., Conclusions: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes., Competing Interests: Disclosures None.

Objective: To investigate the postoperative lymph node metastasis status and related factors of patients with early-stage low-risk endometrial cancer evaluated by the Mayo criteria in order to make the preoperative evaluation more accurate. Methods: A total of 172 patients with early-stage low-risk endometrial cancer who underwent surgery in Sichuan Provincial Cancer Hospital from 2009 to 2018 and were evaluated as early low-risk according to the "Mayo criteria" were retrospectively enrolled, and were divided into lymph node metastasis group (7 cases) and non-metastasis group (165 cases) according to the results of postoperative pathological examination. The postoperative pathological examination results and prognosis of all patients were collected. The lymph node metastasis of the two groups was analyzed. The multiple logistic regression model was used to analyze the related factors of lymph node metastasis, and the area under the curve (AUC) of the relevant factors was calculated by using the receiver operating characteristic curve to predict the postoperative lymph node metastasis of patients. Results: The age of 172 patients was (53.0±8.6) years, and the follow-up [ M ( Q 1 , Q 3 )] was 64.1 (46.2, 91.4) months, among whom 2 relapsed and 1 died. Among the 7 patients with lymph node metastasis, 5 cases had pelvic lymph node metastasis, 1 case had pelvic lymph union and abdominal para-aortic lymph node metastasis, 1 case had isolated abdominal para-aortic lymph node metastasis, 3 cases had two lymph node metastases, and 4 cases had intrailiac lymph nodes being the most common metastasis site. Multivariate analysis showed that preoperative serum cancer antigen (CA) 125 was the relevant factor for postoperative lymph node metastasis, with an OR value (95% CI ) of 1.022 (1.001-1.043) ( P =0.042), with AUC (95% CI ) of CA125 predicting lymph node metastasis of 0.850 (0.761-0.939) ( P =0.002), and the optimal cut-off value of CA125 was 29.305 U/ml with the sensitivity of 85.7% and the specificity of 80.6%. Conclusions: When CA125>29.305 U/ml, patients with early-stage low-risk endometrial cancer assessed by the Mayo criteria, had an increased risk of lymph node metastasis. Therefore, adding preoperative serum CA125 level as an evaluation index on the basis of the classic "Mayo criteria" may help conduct more accurate preoperative evaluation and better identify early-stage low-risk EC patients.

The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis, suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Identifying the risk factors associated with perioperative mortality is crucial, particularly in older patients. Predicting 6-month mortality risk in older patients based on large datasets can assist patients and surgeons in perioperative clinical decision-making. This study aimed to develop a risk prediction model of mortality within 6 months after noncardiac surgery using the clinical data from 11 894 older patients in China., Materials and Methods: A multicentre, retrospective cohort study was conducted in 20 tertiary hospitals. The authors retrospectively included 11 894 patients (aged ≥65 years) who underwent noncardiac surgery between April 2020 and April 2022. The least absolute shrinkage and selection operator model based on linear regression was used to analyse and select risk factors, and various machine learning methods were used to build predictive models of 6-month mortality., Results: The authors predicted 12 preoperative risk factors associated with 6-month mortality in older patients after noncardiac surgery. Including laboratory-associated risk factors such as mononuclear cell ratio and total blood cholesterol level, etc. Also including medical history associated risk factors such as stroke, history of chronic diseases, etc. By using a random forest model, the authors constructed a predictive model with a satisfactory accuracy (area under the receiver operating characteristic curve=0.97)., Conclusion: The authors identified 12 preoperative risk factors associated with 6-month mortality in noncardiac surgery older patients. These preoperative risk factors may provide evidence for a comprehensive preoperative anaesthesia assessment as well as necessary information for clinical decision-making by anaesthesiologists., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic., Methods: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery., Results: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic., Limitation: The absence of data from the early days of the COVID-19 outbreak., Conclusions: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Rhabdias kafunata (Rhabditida: Rhabdiasidae) is a parasitic nematode that significantly affects bufonids. To better understand the genome-level characteristics of related species, Illumina sequencing was used to identify mitochondrial genes and analyze their basic characteristics and gene arrangements. The mitogenome of R. kafunata is 14,068 bp in length and contains 36 genes, including 12 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one noncoding region (NCR). The nucleotide composition is highly biased toward A + T, accounting for 75.5% of the entire mitochondrial genome. The cox1 sequence is relatively conserved in Ka/Ks analyses and can be used as a gene fragment for species identification. While 8 of the 12 PCGs use the typical ATN initiation codon, nad1-2, nad4, and cox3 utilize a TTG initiation codon. Most stop codons end with the standard TAA or TAG, except for cytb, which ends with an incomplete TA. Additionally, trnM, trnK, and trnI have the typical clover-leaf secondary structure, while the remaining tRNAs lack the DHU arm or TΨC arm. Phylogenetic analysis indicates that R. kafunata belongs to the Rhabditidae family and is closely related to Litoditis marina and Caenorhabditis angaria among sequenced lepidopteran mitochondrial genomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personalrelationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Osteoporosis is a metabolic condition distinguished by the degradation of bone microstructure and mechanical characteristics. Traditional Chinese medicine (TCM) has been employed in China for the treatment of various illnesses. Naringin, an ingredient found in Drynariae TCM, is known to have a significant impact on bone metabolism. For this research, we studied the precise potential effect of Drynaria Naringin on protecting against bone loss caused by stress deficiency. In this study, a tail-suspension (TS) test was performed to establish a mouse model with hind leg bone loss. Some mice received subcutaneous injections of Drynaria Naringin for 30 d. Trabecular bone microarchitecture was evaluated using micro-computed tomography analysis and bone histological analysis. Bone formation and resorption markers were quantified in blood samples from mice or in the supernatant of MC3T3-E1 cells by ELISA analysis, Western blotting, and PCR. Immunofluorescence was utilized to visualize the location of β-catenin. Additionally, siRNA was employed to knockdown-specific genes in the cells. Our findings highlight the efficacy of Drynaria Naringin in protecting against the deterioration of bone loss and promoting bone formation and Rspo1 expression in a mouse model following the TS test. Specifically, in vitro experiments also indicated that Drynaria Naringin may promote osteogenesis through the Wnt/β-catenin signalling pathway. Moreover, our results suggest that Drynaria Naringin upregulates the expression of Rspo1/Lgr4, leading to the promotion of osteogenesis via the Wnt/β-catenin signalling pathway. Therefore, Drynaria Naringin holds potential as a therapeutic medication for osteoporosis. Drynaria Naringin alleviates bone loss deterioration caused by mechanical stress deficiency through the Rspo1/Lgr4-mediated Wnt/β-catenin signalling pathway., (© 2023. The Society for In Vitro Biology.)

Background: The mortality rate from septic shock in patients with hematological malignancies (HMs) remains significantly higher than that in patients without HMs. A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients. Shortening the resuscitation time through continuous renal replacement therapy (CRRT) with oXiris ® would be an attractive strategy in managing such patients., Aim: To explore the effects of CRRT and oXiris ® in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels., Methods: Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022. Patients were divided into two groups based on the hemofilter used for CRRT (oXiris ® group, n = 26; M150 group, n = 19). We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups. The heart rate, norepinephrine dose, Sequential Organ Failure Assessment (SOFA) score, and blood lactic acid levels at different time points in the two groups were also compared. Blood levels of inflammatory mediators in the 26 patients in the oXiris ® group were measured to further infer the possible mechanism., Results: The average total fluid balance after 7 d of CRRT in the oXiris ® group was significantly lower than that of patients in the M150 hemofilter group. The SOFA scores of patients after CRRT with oXiris ® therapy were significantly lower than those before treatment on day 1 (d1), d3 and d7 after CRRT; these parameters were also significantly lower than those of the control group on d7. The lac level after oXiris ® therapy was significantly lower than that before treatment on d3 and d7 after CRRT. There were no significant differences in the above parameters between the two groups at the other time points. In the oXiris ® group, procalcitonin levels decreased on d7, whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment., Conclusion: CRRT with oXiris ® hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Glycogen synthase kinase 3β (GSK-3β) is a potential target for anti-Alzheimer's disease (AD) drug development. In this study, a series of novel thieno[3,2-c]pyrazol-3-amine derivatives was synthesized and evaluated as potential GSK-3β inhibitors by structure-based drug design. The thieno[3,2-c]pyrazol-3-amine derivative 54 with a 4-methylpyrazole moiety which interacted with Arg141 by π-cation interaction was identified as a potent GSK-3β inhibitor with an IC 50 of 3.4 nM and an acceptable kinase selectivity profile. In the rat primary cortical neurons, compound 54 showed neuroprotective effects on Aβ-induced neurotoxicity. Western blot analysis indicated that 54 inhibited GSK-3β by up-regulating the expression of phosphorylated GSK-3β at Ser9 and down-regulating the expression of phosphorylated GSK-3β at Tyr216. Meanwhile, 54 decreased tau phosphorylation at Ser396 in a dose-dependent way. In astrocytes and microglia cells, 54 inhibited the expression of inducible nitric oxide synthase (iNOS), indicating that 54 showed an anti-neuroinflammatory effect. In the AlCl 3 -induced zebrafish AD model, 54 significantly ameliorated the AlCl 3 -induced dyskinesia, demonstrating its anti-AD activity in vivo., 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 © 2023 Elsevier Inc. All rights reserved.)

Cryptochrome 1 (CRY1) functions as a light-responsive photoreceptor, which is crucial for circadian rhythms. The identity and function of CRY1 in Plutella xylostella remain unknown. In this study, cry1 was cloned and identified in P. xylostella. Then, a cry1-knockout strain (Cry1-KO) of P. xylostella with a 2-bp deletion was established from the strain Geneva 88 (G88) using the CRISPR/Cas9 technology. No daily temporal oscillation of cry1 was observed in G88 and Cry1-KO, and cry1 mean daily transcription of Cry1-KO was lower than that of G88. Both G88 and Cry1-KO demonstrated rhythmic locomotion under the light/dark condition with Cry1-KO being more active than G88 in the daytime, whereas Cry1-KO completely lost rhythmicity under constant darkness. The developmental period of pre-adult of Cry1-KO was longer than that of G88; the lifespan of the Cry1-KO male adult was shorter than that of G88; the fecundity of Cry1-KO was lower than that of G88; and Cry1-KO showed lower intrinsic rate of increase (r), net reproduction rate (R 0 ), finite increase rate (λ), and longer mean generation time (T) than G88. Our results indicate that cry1 is involved in the regulation of locomotor circadian rhythm and development in P. xylostella, providing a potential target gene for controlling the pest and a basis for further investigation on circadian rhythms in lepidopterans., (© 2022 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Background: Insertion and deletion (InDel) polymorphisms have considerable potential in the field of forensic genetics because of their low mutation rate and small amplicons. At present, InDel polymorphisms detection based on the technique of capillary electrophoresis is the main technique used in forensic DNA laboratory. However, this method is complicated and time-consuming, and is not suitable for rapid on-site paternity and personal identification. Next-generation sequencing analysis of InDels polymorphisms requires expensive instruments, large upfront reagent and supply costs, computational requirements and complex bioinformatics, increased the time to obtain results. Thus, there is an urgent need to establish a method to provide reliable, rapid, sensitive and economical genotyping for InDels., Method: A rapid InDels (32 InDels) panel was established using fluorogenic probes-based multiplex real-time PCR with microfluidic test cartridge and portable real-time PCR instrument. Then, we performed several validation studies including concordance, accuracy, sensitivity, stability, species specificity., Results: It showed that the complete genotypes could be obtained from ≥100 pg of input DNA and from a series of challenging samples with high accuracy and specificity within 90 min., Conclusion: This method provides a rapid and cost-effective solution for InDels genotyping and personal identification in portable format., 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 © 2023 Elsevier Inc. All rights reserved.)

In this study, the transmittance of tanshinone Ⅱ&#95;A(Tan Ⅱ&#95;A) and cryptotanshinone(CTS) through the blood-prostate barrier and their distributions in the prostate tissue were compared between tanshinone extract(Tan E) treatment group and the corresponding monomer composition group under the equivalent dose conversion in vitro and in vivo. First, the human prostate epithelial cell line RWPE-1 was cultured in vitro for 21 days for the establishment of a blood-prostate barrier model, and the transmission of Tan Ⅱ&#95;A and CTS through the barrier model was investigated after administration of Tan E and corresponding single active components. Second, SD rats were administrated with 700 mg·kg~(-1) Tan E, 29 mg·kg~(-1) CTS, and 50 mg·kg~(-1) Tan Ⅱ&#95;A by gavage, and plasma and prostate tissue samples were collected at the time points of 2, 4, 8, 12, and 24 h. The Tan Ⅱ&#95;A and CTS concentrations in the samples were determined. The results showed that in the cell model, the cumulative transmission amounts of CTS and Tan Ⅱ&#95;A in the extract at each time point were higher than those of the corresponding single active components(P&lt;0.01). In rats, after the administration of Tan E, the concentrations of Tan Ⅱ&#95;A and CTS in rat plasma and prostate were higher than those of the corresponding single active components. This study demonstrated that the coexisting components in Tan E promoted the penetration of its main pharmacological components Tan Ⅱ&#95;A and CTS through the blood-prostate barrier. The findings provide a theoretical and experimental basis for the application of Tan E in the clinical treatment of prostate-related diseases.

Objective: Compensation characteristics of spinal sagittal malalignment according to pelvic incidence (PI) have yet to be elucidated. This study aimed to investigate the difference in compensatory segments according to PI in elderly patients with degenerative lumbar spinal stenosis (DLSS)., Methods: This retrospective study included 196 patients (143 females, 53 males) suffering from DLSS with an average age of 66.73 years in our department. Sagittal parameters were obtained on the whole spinal lateral radiograph, including T1-T12 slope (T1S-T12S), Cobb angle (CA) of the functional units of the thoracic spine, thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), PI, the ratio of PT to PI (PT/PI), PI minus LL mismatch (PI-LL), sagittal vertical axis (SVA). Patients were divided into the low and high PI groups according to the median value of PI. With reference to the value of SVA and PI-LL, each PI group was further grouped into the balance subgroup (SVA < 50 mm, PI-LL ≤10°), hidden imbalance subgroup (SVA < 50 mm, PI-LL > 10°), and imbalance subgroup (SVA ≥50 mm). Independent samples t-test/Mann-Whitney U test, one-way ANOVA/Kruskal-Wallis test, and Person correlation analysis were utilized for statistical test., Results: The median value of PI was 47.65°. 96 and 100 patients were assigned to low and high PI groups, respectively. Correlation analysis indicated that the T8-T12 slope and T10-T12 slope were associated with PI-LL in the high and low PI groups, respectively (all, p < 0.01). For segmental lordosis, T8-9 to T11-12 CA and T10-11 to T11-12 CA were associated with PI-LL in the high and low PI groups, respectively (all, p < 0.01). In the high PI cohort, T8-12 CA and PT increased significantly from the balance to imbalance subgroups (both, p < 0.05). In the low PI cohort, T10-12 CA and PT first increased and then decreased from the balance to imbalance subgroups (both, p < 0.05)., Conclusion: T8-12 was the main compensatory segment of the thoracic spine in patients with high PI, while it was T10-12 in patients with low PI. In addition, the compensation potential of the lower thoracic spine and pelvis in patients with low PI was inferior to those with high PI., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: The effective treatment for hepatocellular carcinoma (HCC) depends on early diagnosis. Previously, the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/β-catenin pathway was found in HCC cells and could be released into the circulation. In this study, we used rat model of hepatocarcinogenesis to dynamically investigate the alteration of oncogenic Wnt3a and to explore its early monitor value for HCC., Methods: Sprague-Dawley rats (SD) were fed with diet 2-fluorenylacetamide (2-FAA, 0.05%) for inducing hepatocarcinogenesis, and grouped based on liver morphological alteration by Hematoxylin & Eosin (H&E) staining; rats fed with normal chow were used as normal control (NC). Total RNA and protein were purified from rat livers. Differently expressed genes (DEGs) or Wnt3a mRNA, cellular distribution, and Wnt3a protein levels were analyzed by whole genome microarray with signal logarithm ratio (SLR log 2 cy5/cy3 ), immunohistochemistry, and enzyme-linked immunosorbent assay, respectively., Results: Models of rat hepatocarcinogenesis were successfully established based on liver histopathological H&E staining. Rats were divided into the cell degeneration (rDeg), precancerosis (rPre-C) and HCC (rHCC) groups. Total numbers of the up- and down-regulated DEGs with SLR ≥ 8 were 55 and 48 in the rDeg group, 268 and 57 in the rPre-C group, and 312 and 201 in the rHCC group, respectively. Significantly altered genes were involved in cell proliferation, signal transduction, tumor metastasis, and apoptosis. Compared with the NC group, Wnt3a mRNA was increased by 4.6 folds (P < 0.001) in the rDeg group, 7.4 folds (P < 0.001) in the rPre-C group, and 10.4 folds (P < 0.001) in the rHCC group; the positive rates of liver Wnt3a were 66.7% (P = 0.001) in the rDeg group, 100% (P < 0.001) in the rPre-C group, and 100% (P < 0.001) in the rHCC group, respectively. Also, there were significant differences of liver Wnt3a (P < 0.001) or serum Wnt3a (P < 0.001) among different groups., Conclusions: Overexpression of Wnt3a was associated with rat hepatocarcinogenesis and it should be expected to be a promising monitoring biomarker for HCC occurrence at early stage., (Copyright © 2022 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

The work aimed to assess the antioxidant ability and obtain a new antioxidant peptide from rice bran protein. Rice bran protein was hydrolyzed by Alcalase, Neutral, Pepsin, Chymotrypsin, and Trypsin, separately. Trypsin hydrolysate (T-RBPH) showed high Fe 2+ chelating activity (IC 50 , 2.271 ± 0.007 mg/mL), DPPH and hydroxyl radical scavenging ability (IC 50 , 0.191 ± 0.006 and 1.038 ± 0.034 mg/mL). Moreover, T-RBPH could alleviate the H 2 O 2 -induced oxidative damage in Caco-2. The T-RBPH was purified and identified by UF, GF, FPLC, and LC-MS/MS. Finally, 9-amino acid peptide-AFDEGPWPK with low molecular weight (1045.48 Da), high antioxidant activity, good safety, and solubility was screened by in silico method and chemical oxidation determination, and its interaction with Keap1 was also demonstrated. The ORAC and DPPH radical scavenging ability of AFDEGPWPK were 44.16 ± 0.79 and 28.38 ± 0.14 μmol TE/mM. Moreover, the Molecular docking and Western blot (WB) results showed that AFDEGPWPK could enter the binding pocket in the Kelch domain and activate Keap1/Nrf2/HO-1 pathway., 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 © 2022 Elsevier Ltd. All rights reserved.)

Goats with diverse economic phenotypic traits play an important role in animal husbandry. However, the genetic mechanisms underlying complex phenotypic traits are unclear in goats. Genomic studies of variations provided a lens to identify functional genes. In this study, we focused on the worldwide goat breeds with outstanding traits and used whole-genome resequencing data in 361 samples from 68 breeds to detect genomic selection sweep regions. We identified 210-531 genomic regions with six phenotypic traits, respectively. Further gene annotation analysis revealed 332, 203, 164, 300, 205, and 145 candidate genes corresponding with dairy, wool, high prolificacy, poll, big ear, and white coat color traits. Some of these genes have been reported previously (e.g., KIT , KITLG , NBEA , RELL1 , AHCY, and EDNRA ), while we also discovered novel genes, such as STIM1 , NRXN1 , LEP , that may be associated with agronomic traits like poll and big ear morphology. Our study found a set of new genetic markers for genetic improvement in goats and provided novel insights into the genetic mechanisms of complex traits., 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 © 2023 Wan, Jing, Wang and Lv.)

Background: The impact of sarcopenia on textbook outcome (TO) after hepatectomy in hepatocellular carcinoma (HCC) patients remains unclear. This study aimed to investigate the association between sarcopenia and TO, to clarify its long and short-term prognostic value, and to develop a nomogram model based on sarcopenia and TO for survival prediction., Methods: Patients who underwent HCC resection between January 2012 and March 2017 in three large hospitals in Fujian were retrospectively recruited and divided into sarcopenia and non-sarcopenia groups based on skeletal muscle index (SMI) values. TO was defined as no 30-day morality, no 30-day readmission, negative margins, no prolonged hospital stay, and no major complications. Multivariate regression was used to screen for clinical factors associated with TO. Nomograms of overall survival (OS) and recurrence-free survival (RFS) after hepatectomy for HCC were developed., Results: A total of 1172 patients were included in the study. The TO rates were 28.74% (121/421 patients) in the sarcopenia group and 43.4% (326/751 patients) in the non-sarcopenia group. The results showed that sarcopenia was an independent predictor of TO (p < 0.001), TO was an independent predictor of perioperative treatment-related sarcopenia (PTRS)(p = 0.002), and TO was an independent predictor of OS and RFS (p < 0.001). Nomogram models based on sarcopenia and TO were generated and accurately predicted OS and RFS at 1, 3, and 5 years., Conclusion: Both sarcopenia and TO are independent predictors of OS and RFS after HCC resection. Sarcopenia was an independent predictor of TO. Sarcopenia influenced long-term survival by affecting short-term postoperative outcomes., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: The aim of this study was to investigate the association between spinal alignment and preoperative patient-reported outcomes (PROs) in patients with degenerative lumbar spondylolisthesis (DLS) and to identify the independent risk factors for worse preoperative PROs., Methods: In total, 101 patients suffering from DLS were retrospectively studied within a single medical center. Age, sex, height, weight, and body mass index were uniformly recorded. PRO-related indicators include the Oswestry Disability Index (ODI), the Japanese Orthopedic Association's (JOA) score, and the visual analog scale (VAS) for back and leg pain. Sagittal alignment, coronal balance, and stability of the L4/5 level were evaluated through whole-spine anteroposterior and lateral radiographs and dynamic lumbar X-ray., Results: Increasing age (P = 0.005), higher sagittal vertical axis (SVA) (P < 0.001), and global coronal imbalance (GCI) (P = 0.023) were independent risk factors for higher ODI. Patients with GCI had lower JOA scores (P = 0.001) than those with balanced coronal alignment. Unstable spondylolisthesis (P < 0.001) and GCI (P = 0.009) were two vital predictors of VAS-back pain. Increasing age (P = 0.031), local coronal imbalance (LCI) (P < 0.001), and GCI (P < 0.001) were associated with higher VAS-leg pain. Moreover, patients with coronal imbalance also exhibited significant sagittal malalignment based on the subgroup analysis., Conclusion: DLS patients with higher SVA, unstable spondylolistheses, a combination of LCI/GCI, or increasing age were predisposed to have more severe subjective symptoms before surgery., (© 2023. The Author(s).)

Objective: To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS)., Methods: We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors., Results: Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2-32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081-9.757, P = 0.036)., Conclusions: PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This retrospective cross-sectional study investigated variations in the ratio of cervical lordosis to C7 slope (CL/C7S) at different stages of global sagittal balance to better understand how global sagittal alignment affects cervical alignment., Methods: A total of 255 patients with the degenerative lumbar disease were retrospectively studied within a single medical center. Whole spine radiographs were used to evaluate sagittal parameters, mainly including occiput-C2 lordosis (OC2), cervical lordosis (CL), C7 slope (C7S), the ratio of cervical lordosis to C7 slope (CL/C7S), cervical sagittal vertical axis (CSVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), PI minus LL mismatch (PI-LL), and sagittal vertical axis (SVA). Patients were divided into the balance group (SVA < 50 mm, PI-LL ≤ 10°), hidden imbalance group (SVA < 50 mm, PI-LL > 10°), and imbalance group (SVA > 50 mm)., Results: Significant correlations were found between CL/C7S and OC2 (r = - 0.334), CSVA (r = - 0.504), PI-LL (r = 0.189), and SVA (r = 0.309). Multivariable linear regression analysis indicated that patients in the hidden imbalance group had lower CL/C7S than those in the balance group (B = - 0.234, P < 0.001), whereas the value of CL/C7S in patients with imbalanced sagittal alignment was higher than those with balanced alignment (B = 0.164, P = 0.011). The mean value of CL/C7S was 0.71, 0.51, and 0.97 in the balance, hidden imbalance, and imbalance groups, respectively. The global spine tended to tilt forward as the LL decreased, while TK, PT, PI-LL, and SVA increased (all, P < 0.001) from the balance stage to the imbalance stage., Conclusions: CL/C7S tended to be lower when the thoracic extension increased to maintain global sagittal balance at the hidden imbalance stage. Inversely, CL/C7S increased significantly when the global spine showed severe anterior malalignment., (© 2023. The Author(s).)

Purpose: To investigate the effect of interlaminar Coflex stabilization (ICS) at various segments in the topping-off procedure on local and global spinal sagittal alignment., Methods: Eighty-nine consecutive patients with degenerative lumbar spinal stenosis (DLSS) who underwent ICS and transforaminal lumbar interbody fusion (TLIF) were retrospectively reviewed. They were divided into Group A (L4-L5 ICS + L5-S1 TLIF), Group B (L3-L4 ICS + L4-S1 TLIF), and Group C (L2-L3 ICS + L3-S1 TLIF) according to their fusion levels. The measured local sagittal parameters included the implanted segmental angle (ISA), intervertebral disc angle (IDA), intervertebral foreman height (IFH), and disc height. The assessed global sagittal parameters included thoracic kyphosis, lumbar lordosis (LL), the fused segment angle (FSA), the sacral slope, the pelvic tilt, pelvic incidence, and the sagittal vertical axis. The Oswestry Disability Index (ODI) and visual analog scales (VAS) were recorded to evaluate the clinical outcomes., Results: Regarding the local alignment parameters, the ISA and IDA decreased immediately after surgery in Groups A and B, followed by an increase at the last follow-up (all, P < 0.05). Conversely, the IFH of Groups A and B first increased after surgery and then decreased to approximately the original value (all, P < 0.05). No significant differences were evident between the local sagittal parameters at different time points in Group C. Regarding the global sagittal profiles, the LL and FSA exhibited a significant postoperative increase (both at P < 0.05) in all the groups. All three groups displayed significant improvements in the ODI, VAS-back pain, and VAS-leg pain. Furthermore, 4.5% (4/89) of the patients exhibited radiographic adjacent segment degeneration (ASD) at the last follow-up., Conclusion: ICS during topping-off surgery led to a temporary loss of local lordosis, especially in the lower lumbar segment, while the intervertebral space realigned after middle-term follow-up. The topping-off procedure with ICS is a feasible and promising surgical option of DLSS since it reduces fusion levels and prevents ASD development., (© 2023. The Author(s).)

Purpose: To identify the relationship between depression measured by Zung depression rating scale (ZDRS) and postoperative outcomes (including the patients reported outcomes [PRO] and clinical outcomes) two years after short-segment fusion surgery for degenerative lumbar spinal disease in older patients (aged 75 years and older)., Methods: We enrolled patients who underwent short-segment fusion surgery for lumbar degenerative disease from May 2018 to June 2020. All patients were assessed for depression using the ZDRS. Patients were included in the depression group and not-depressed group based on their scores. Preoperative baseline data were collected on characteristics, comorbidities, laboratory data, pain levels (visual analogue scale [VAS]), functional status (Oswestry Disability Index [ODI]), and surgery-related variables. The primary outcomes were PRO measures, including VAS, ODI and satisfaction two years after lumbar fusion surgery. Other outcomes included postoperative complications, the length of stay, and reoperation. Univariate and multivariate analyses were performed to identify the risk factors for poor satisfaction., Results: A total of 231 patients (201 in not-depressed and 30 in depressed group) were enrolled in this study. There were no significant differences between the two groups for baseline data. Depressed group had higher rates of choices for dissatisfaction (36.7% vs. 14.0%, p = 0.015), higher VAS scores of low back pain (2.8 ± 2.3 vs. 1.6 ± 1.7, p = 0.012), and worse functional status (31.5 ± 22.5 vs 21.8 ± 19.9, p = 0.015) than the not-depressed group. Depressed patients reported significantly higher rates of postoperative complications and readmissions. Multivariate regression analysis revealed that depression (p = 0.001) was independently associated with postoperative dissatisfaction., Conclusion: Preoperative depression was a risk factor for postoperative dissatisfaction, worse functional status, readmission, and complications in older patients undergoing lumbar fusion surgery. Preoperative screening using the Zung depression scale helps inform decision-making when considering fusion surgery for patients aged 75 and older., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

BACKGROUND Plantar pressure analysis is widely used in the study of knee osteoarthritis (KOA). The present study aimed to investigate the static and dynamic plantar pressure distribution in patients with different stages of unilateral KOA using the Footscan® platform system. MATERIAL AND METHODS We recruited 94 patients aged 61.75±7.23 years old with different stages of unilateral KOA for static and dynamic analysis using the Footscan® platform system. The static pressure (%) of the left, right, anterior, posterior, and the pelvic rotation (°) was assessed. The peak pressure (PP, kPa) was investigated in 10 areas of the foot: medial heel (MH), lateral heel (LH), midfoot (MF), first to fifth metatarsals (M1-M5), hallux (T1), and toes 2-5 (T2-5). The correlation between KOA stages and plantar pressure distributions was investigated. RESULTS The results revealed that static pressure on the unaffected side and pelvic rotation were positively correlated with KOA stages. In addition, there was a positive correlation between KOA stages and PP of M5, MF, and LH zones on the affected side and PP of M2, M3, and M4 zones on the unaffected side, and a negative correlation between KOA stages and PP of T1 and T2-5 zones on the affected side. CONCLUSIONS With the progression of KOA, static plantar pressure tends to distributed on the unaffected side, and the dynamic plantar pressure tends to be distributed laterally on both feet. The plantar pressure distributions in unilateral KOA patients are abnormal and are closely related to the severity of KOA.

Broken rice is an important by-product during milling process of rice, which is rich in protein. To increase the value of by-products and search for effective antioxidants, the antioxidant peptides from broken rice protein hydrolysate were separated and identified by ultrafiltration, gel filtration chromatography, fast protein liquid chromatography, and LC-MS/MS in this study. These identified peptides were further screened using a combined in silico and in vitro method and their antioxidant mechanism was explored by Western blot and molecular docking analysis. Ninety-eight peptides were obtained after antioxidant activity-oriented isolation and four novel peptides, SGDWSDIGGR, DFGSEILPR, GEPFPSDPKKQLQ, and GEKGGIPIGIGK, with excellent solubility, safety, and antioxidant activity were synthesized. Among these, SGDWSDIGGR showed good antioxidant activities in the extracellular assay (41.57 μmol TE/g and 29.41 % in ORAC and DPPH assay, respectively.), and it possessed a protective effect against H 2 O 2 -injured oxidative stress in 2BS cells in a dose-dependent manner. Furthermore, Western blot and molecular docking results showed that SGDWSDIGGR achieves antioxidant ability by occupying the Nrf2-binding site, activating the Keap1-Nrf2 signaling pathway, and upregulating the expression of antioxidant enzymes. This study extends the rice industry chain and provides insights into the selection and mechanisms research of antioxidant peptides., 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 © 2022 Elsevier Ltd. All rights reserved.)

Glycogen synthase kinase 3β (GSK-3β) catalyses the hyperphosphorylation of tau protein in the Alzheimer's disease (AD) pathology. A series of novel thieno[3,2- c ]pyrazol-3-amine derivatives were designed and synthesised and evaluated as potential GSK-3β inhibitors by structure-guided drug rational design approach. The thieno[3,2- c ]pyrazol-3-amine derivative 16b was identified as a potent GSK-3β inhibitor with an IC 50 of 3.1 nM in vitro and showed accepted kinase selectivity. In cell levels, 16b showed no toxicity on the viability of SH-SY5Y cells at the concentration up to 50 μM and targeted GSK-3β with the increased phosphorylated GSK-3β at Ser9. Western blot analysis indicated that 16b decreased the phosphorylated tau at Ser396 in a dose-dependent way. Moreover, 16b effectively increased expressions of β-catenin as well as the GAP43, N-myc, and MAP-2, and promoted the differentiated neuronal neurite outgrowth. Therefore, the thieno[3,2- c ]pyrazol-3-amine derivative 16b could serve as a promising GSK-3β inhibitor for the treatment of AD.

Introduction: Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC., Methods: Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared., Results: The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009)., Conclusions: Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes., (© 2022. The Author(s).)

Background: Insulin-like growth factor-1 receptor (IGF-1R) is over-expressed in hepatocellular carcinoma (HCC). However, the relationship between IGF-1R activation and HCC progression remains unidentified., Aim: To investigate the effects of editing IGF-1R on the biological features of HCC cells., Methods: Immunohistochemistry analyzed the expressions of IGF-1R and P-glyco protein (P-gp) in HCC tissues and their distal non-cancerous tissues (non-Ca). IGF-1R was edited with Crispr/Cas9 system, screened specific sgRNAs, and then transfected into HepG2 cells. CCK-8, scratch wound test detected cell proliferation, migration, invasion and transwell assays, respectively. Alterations of IGF-1R and P-gp were confirmed by Western blotting. Alterations of anti-cancer drug IC 50 values were analyzed at the cell level., Results: The positive rates of IGF-1R (93.6%, χ 2 = 63.947) or P-gp (88.2%, χ 2 = 58.448) were significantly higher ( P < 0.001) in the HCC group than those (36.6% in IGF-1R or 26.9% in P-gp) in the non-Ca group. They were positively correlated between high IGF-1R and P-gp expression, and they were associated with hepatitis B virus infection and vascular invasion of HCC. Abnormal expressions of circulating IGF-1R and P-gp were confirmed and associated with HCC progression. Biological feature alterations of HCC cells transfected with specific sgRNA showed IGF-1R expression down-regulation, cell proliferation inhibition, cell invasion or migration potential decreasing, and enhancing susceptibility of HepG2 cells to anti-cancer drugs., Conclusion: Edited oncogenic IGF-1R was useful to inhibit biological behaviors of HepG2 cells., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored. Methods: (1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed. Results: (1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P <0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95% CI : 25.9-33.6 months), and the median overall survival was 49.8 months (95% CI : 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P <0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P <0.05). Conclusions: Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

Purpose: To investigate the influence of changes in T1 slope (T1S) and cervical sagittal vertical axis (CSVA) on cervical laminoplasty outcomes., Methods: Eighty-one patients with cervical spondylotic myelopathy (CSM) treated with cervical laminoplasty were enrolled in this study. Demographic parameters included age and follow-up time. Imaging data included occiput-C2 lordosis (OC2), C2-C7 Cobb angle (CL), T1S, CSVA. Outcome assessment indicators included the Japanese Orthopedic Association (JOA) score, JOA recovery rate, and neck disability index (NDI). All patients were grouped based on preoperative T1S and variation in CL after surgery, respectively. Patients with decreased CL postoperatively were further grouped according to whether they were combined with T1S reduction., Results: There were no significant differences in the final JOA score, JOA recovery rate, or NDI between patients with different T1S. Patients with loss of CL postoperatively had lower JOA score and JOA recovery rate, but higher NDI than patients with sustained CL. Furthermore, patients with CL loss but compensate for it with reduction in T1S had lower CSVA, higher JOA score and JOA recovery rate than those with CL loss alone., Conclusions: Decreased T1S postoperatively prevents the tendency of the cervical spine to tilt forward by regulating CSVA and facilitates recovery of neurological function after cervical laminoplasty., 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., (© 2022 Wang, Li, Kong, Liu, Shi and Lu.)

Background: During the COVID-19 pandemic, wearing PPE can induce skin damage such as erythema, pruritus, erosion, and ulceration among others. Although the skin microbiome is considered important for skin health, the change of the skin microbiome after wearing PPE remains unknown., Objective: The present study aimed to characterize the diversity and structure of bacterial and fungal flora on skin surfaces of healthcare workers wearing personal protective equipment (PPE) during the COVID-19 pandemic using metagenomic next-generation sequencing (mNGS)., Methods: A total of 10 Chinese volunteers were recruited and the microbiome of their face, hand, and back were analysed before and after wearing PPE. Moreover, VISIA was used to analyse skin features., Results: Results of alpha bacterial diversity showed that there was statistically significant decrease in alpha diversity indice in the skin samples from face, hand, and three sites after wearing PPE as compared with the indice in the skin samples before wearing PPE. Further, the results of evaluated alpha fungal diversity show that there was a statistically significant decrease in alpha diversity indices in the skin samples from hand after wearing PPE as compared with the indices in the skin samples before wearing PPE (P < 0.05). Results of the current study found that the main bacteria on the face, hand, and back skin samples before wearing the PPE were Propionibacterium spp. (34.04%), Corynebacterium spp. (13.12%), and Staphylococcus spp. (38.07%). The main bacteria found on the skin samples after wearing the PPE were Staphylococcus spp. (31.23%), Xanthomonas spp. (26.21%), and Cutibacterium spp. (42.59%). The fungal community composition was similar in three skin sites before and after wearing PPE., Conclusion: It was evident that wearing PPE may affect the skin microbiota, especially bacteria. Therefore, it was evident that the symbiotic microbiota may reflect the skin health of medical workers during the COVID-19 pandemic., (© 2022 European Academy of Dermatology and Venereology.)

Objective: Cervical sagittal parameters have been widely used to predict clinical outcomes in patients with cervical spondylotic myelopathy (CSM). This study aims to coin a novel cervical sagittal parameter defined as the ratio of cervical sagittal vertical axis to T1 slope (CSVA/T1S) and to investigate the correlation between CSVA/T1S and postoperative HRQOL after laminoplasty., Methods: A total of 102 CSM patients treated with cervical laminoplasty from our database were retrospectively reviewed. All patients were followed up for >12 months. Radiological parameters were measured using lateral cervical radiographs, including occiput-C2 lordosis (OC2), cervical lordosis (CL), CSVA, and T1S. Clinical parameters included the Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and JOA recovery rate. Patients were grouped by preoperative T1S, T1S-CL, and CSVA/T1S value, respectively. Clinical and radiological outcomes were compared between the groups., Results: Patients with high CSVA/T1S had greater OC2 and CSVA but lower CL than those in the low CSVA/T1S group pre-and postoperatively. With respect to HRQOL results, the final NDI was 12.46 ± 9.11% in the low CSVA/T1S group, which was significantly lower than that in the high CSVA/T1S group (17.68 ± 8.81%, P  = 0.040). Moreover, only CSVA/T1S was detected to be significantly correlated with final NDI ( r  = 0.310, P  = 0.027). No significant correlation was found between clinical results and other cervical sagittal parameters, including T1S, CSVA, and T1S-CL., Conclusions: Preoperative CSVA/T1S was correlated with postoperative NDI in patients with CSM after cervical laminoplasty. Patients with low preoperative CSVA/T1S achieved better neurological function improvement after cervical laminoplasty. Cervical laminoplasty could be an appropriate choice for patients with lower preoperative CSVA/T1S., 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., (© 2022 Wang, Zhu, Wang, Li, Kong, Liu, Shi and Lu.)