Jiawei-Xiaoyao pill elicits a rapid antidepressant effect, dependent on activating CaMKII/mTOR/BDNF signaling pathway in the hippocampus.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei-Xiaoyao pill (JWX), a traditional Chinese medicine, was recorded in ancient Chinese medicine pharmacopoeia using for treatment of various diseases, including mood disorders. Current mainstream antidepressants have a disadvantage in delayed onset of action. The rapid antidepressant potential of JWX and the underlying mechanisms remain unclear. AIM OF THE STUDY: We aimed to assess the rapid antidepressant potential of JWX, within the prescription dose range, and the distinct underlying neuroplasticity signaling mechanism. MATERIALS AND METHODS: The rapid antidepressant response of JWX were determined using various behavioral paradigms, and in a corticosterone (CORT)-induced depression model in mice. The molecular neuroplasticity signaling and the expression of BDNF in the hippocampus was evaluated using immunoblotting and immunostaining. The contribution of specific signaling was investigated using pharmacological interventions. RESULTS: A single dose of JWX induced rapid and persistent antidepressant effects in both the normal and chronic CORT-exposed mice. The phosphorylation of CaMKII, mTOR, ERK and the expressions of BDNF, synapsin1 and PSD95 increased at 30 min post JWX. JWX restored the expression of BDNF in the hippocampal dentate gyrus reduced by CORT-exposure. The rapid antidepressant effect and upregulation of BDNF expression by JWX was blunted by a mTOR antagonist, rapamycin, or a CaMKII antagonist, KN-93. CaMKII signaling blockade blunted mTOR signaling activated by JWX, but not vice versa. CONCLUSION: JWX elicits a rapid antidepressant effect, via quickly stimulating CaMKII signaling, subsequently activating mTOR-BDNF signaling pathway, and thus enhancing hippocampal neuroplasticity.

Licochalcone A promotes renewal of intestinal mucosa through modulating uc.173.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice can nourish Pi (spleen) and thereby strengthening the digestive system according to the theory of traditional Chinese medicine. Licorice has been generally used in the compound prescription to treat intestinal inflammatory disease. Licochalcone A (Lico A) is one of the characteristic molecules from licorice. T-UCRs, which are transcribed from ultraconserved regions, are a new class of long noncoding RNAs related to the renewal of intestinal epithelial renewal. AIM OF THE STUDY: This study aimed to investigate the effect and the uc.173-related mechanism of Lico A on intestinal epithelial renewal. MATERIALS AND METHODS: IE-6 and Caco-2 cells were used to evaluate the effect of Lico A on apoptosis, proliferation, and migration of IECs. The intestinal organoid was used to investigate ex vivo effect and mechanism of Lico A promoting intestinal organoid development. C57BL/6J mice (both normal and uc.173-deficient ones) were used to examine the in vivo effect of Lico A on the renewal of intestinal mucosa. RESULTS: The expression of three T-UCRs related to the intestinal mucosa renewal was altered in Lico A-treated IECs. Lico A promoted the proliferation and inhibited the apoptosis of IECs through uc.173/miR-195 pathway. The development of intestinal organoids and the renewal of intestinal mucosa of mice subjected to the 48-h FAST were all promoted by the treatment of Lico A. Moreover, the growth arrest of uc.173-deficient intestinal organoids and the atrophy of intestinal mucosa in uc.173-deficient mice could be rescued by the Lico A administration. CONCLUSION: Results in this paper suggest that targeting T-UCRs may be the novel therapeutic approach for the promotion of epithelial regeneration, and through stimulating the regeneration of intestinal mucosa, Lico A may become a new therapeutic agent for the maintenance of intestinal epithelial integrity.

Development and validation of a core competence instrument for clinical nursing teachers: A mixed-methods study.

BACKGROUND: Competence-based education (CBE) highlights the important position of clinical nursing teachers and stipulates additional requirements for them. However, research on the core competence of clinical nursing teachers remains lacking, which has hindered their development and the cultivation of nursing students. OBJECTIVES: Developing and verifying a core competence instrument to evaluate clinical nursing teachers' competence in clinical settings and provide empirical guidance for their development. DESIGN: A mixed-methods study including qualitative and quantitative methods. SETTINGS: Primarily, 9 universities and hospitals throughout China. PARTICIPANTS: Fourteen nursing experts and 2 students participated in the qualitative study, and 626 nursing professionals ultimately participated in the quantitative study. METHODS: The instrument was developed based on behavioral event interviews and expert consultation as well as exploratory factor analysis using a cross-sectional survey, following which the instrument was verified by confirmatory factor analysis. RESULTS: A 4-factor core competence instrument for clinical nursing teachers was developed and verified; the four factors included education and teaching competence, clinical nursing competence, management competence and professional awareness and attitude, and the instrument included 25 items in total. The instrument has an explanatory degree of 90.58 %, and it exhibits good reliability and validity as well as a good fit to the data. CONCLUSIONS: This instrument can provide theoretical guidance for the development of clinical nursing teachers and can be widely used as an effective tool in practice. Nursing administrators and educators should implement policies and programs to help clinical nursing teachers improve their competencies with regard to these four aspects, which can play an important role in the development of nurse education.

Resource utilization of expired progesterone medicines as flow improver for waxy crude oils.

At present, the treatment of expired medicines mainly involves burning, which means waste of resources and carbon dioxide emissions, and it does not comply with the concept of resource recycling. In this study, in order to explore the resource utilization pathways of expired medicines, progesterone drugs were evaluated as crude oil flow improvers as an example. The results shows that progesterone injection (PI) and progesterone capsule (PC) both act as viscosity reducer and pour point depressant in different crude oil, and 500 ppm PI and 300 ppm PC are the best dosage respectively. 500 ppm PI can reduce the viscosity of HN oil sample by 60.40%, and depress the pour point by 8.5 °C. 300 ppm PC can reduce the viscosity of HN oil by 54.7%, and depress the pour point by 10.9 °C. Furthermore, through DSC and wax crystal morphology analysis, the possible mechanism of this expired medicine as crude oil flow improver was further discussed. Finally, considering the costs of concentration, transportation, treatment, processing and other links, the possible cost of crude oil flow improver was summed up, and its market feasibility was analyzed. This study provides a reference case for the resource utilization of expired medicines.

Effects of temperature on the migration behaviour of arsenic and chromium in tannery sludge under CO2 gasification.

To reduce heavy metals (HMs) contamination from tannery sludge, this study investigated the migration behaviour of arsenic (As) and chromium (Cr) at 700-900 °C using CO2 gasification. The HMs enrichment results showed that As contents of ash decreased (6.42→1.87 mg/kg) while Cr contents increased (41.40→78.24 mg/kg) over 700-900 °C. More Si-O bonds and fewer Ca-O bonds with increasing temperature in ash primarily determined this migration behaviour of HMs. Meanwhile, the proportions of toxic As(III) and Cr(VI) declined from 96.02% and 64.26-76.96% and 21.24%, forming As(0) and Cr(III) with less toxicity. This reduction was conducted via two pathways: (i) carbon reduced As(III)/Cr(VI) and (ii) carbon reduced Fe(II)/Fe(III) to Fe(0), then Fe(0) reduced As(III)/Cr(VI) assisted with carbon via Fe(0)→Fe(II)→Fe(III). However, free calcium ions oxidized As(0)/Cr(III) to As(III)/Cr(VI) at 700 ○C. At higher temperatures, silicate glass conversion of ash immobilized free calcium ions and barely oxidized HMs. Furthermore, this study identified the positive effect of increasing temperature on enhancing the stability of HMs in ash by transforming bioavailable HMs into non-bioavailable HMs, which decreased the leaching toxicity and environmental risk. Regarding HMs emissions control and cold gas efficiency, CO2 gasification treatment of tannery sludge is most effective at 800 °C.

The protective effects of sevoflurane on subarachnoid hemorrhage.

Sevoflurane has become an important volatile anesthetic in clinic and has been widely studied in recent years. Numerous studies have demonstrated the efficacy of sevoflurane in safeguarding against brain damage across various domains. For example, it has played a neuroprotective role in subarachnoid hemorrhage (SAH), traumatic brain injury, and ischemia/reperfusion injury. The ensuing critique will focus on the significance of sevoflurane in experimental SAH and shed light on the underlying mechanisms. The findings of the current investigation demonstrate that sevoflurane possesses neuroprotective capabilities and clarify that it effectively attenuates secondary damage resulting from SAH through anti-inflammatory and anti-apoptotic pathways. More specifically, sevoflurane is observed to mitigate arterial vasospasm, diminish microvascular thrombosis, and alleviate cerebral edema. In light of these discoveries, we maintain that sevoflurane exhibits significant promise in the management of SAH, and it merits additional investigation to facilitate its prompt clinical implementation. Therefore, a thorough understanding of the neuroprotective properties of sevoflurane is beneficial to exploring novel therapeutic solutions for SAH and providing clinicians with alternative treatment modalities.

Metabolic and proteostatic differences in quiescent and active neural stem cells.

Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis. Therefore, neural regeneration may be a promising target for treatment of many neurological illnesses. The regenerative capacity of adult neural stem cells can be characterized by two states: quiescent and active. Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool. Active adult neural stem cells are characterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits. This review focuses on differences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis. Furthermore, we discuss the physiological significance and underlying advantages of these differences. Due to the limited number of adult neural stem cells studies, we referred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

An Efficient Single Image De-raining Model with Decoupled Deep Networks.

Single image de-raining is an emerging paradigm for many outdoor computer vision applications since rain streaks can significantly degrade the visibility and render the function compromised. The introduction of deep learning (DL) has brought about substantial advancement on de-raining methods. However, most existing DL-based methods use single homogeneous network architecture to generate de-rained images in a general image restoration manner, ignoring the discrepancy between rain location detection and rain intensity estimation. We find that this discrepancy would cause feature interference and representation ability degradation problems which significantly affect de-raining performance. In this paper, we propose a novel heterogeneous de-raining architecture aiming to decouple rain location detection and rain intensity estimation (DLINet). For these two subtasks, we provide dedicated network structures according to their differential properties to meet their respective performance requirements. To coordinate the decoupled subnetworks, we develop a high-order collaborative network learning the dynamic inter-layer interactions between rain location and intensity. To effectively supervise the decoupled subnetworks during training, we propose a novel training strategy that imposes task-oriented supervision using the label learned via joint training. Extensive experiments on synthetic datasets and real-world rainy scenes demonstrate that the proposed method has great advantages over existing state-of-the-art methods.

Clinical outcomes of modified versus traditional expansive open-door laminoplasty for cervical spondylotic myelopathy: A single-institution experience.

PURPOSE: To compare the surgical outcomes of modified expansive open-door laminoplasty (EOL) (C4-C6) and traditional EOL (C3-C7) in patients with cervical spondylotic myelopathy (CSM). METHODS: One hundred and two CSM patients were retrospectively recruited from Fujian Medical University Union Hospital between March 2012 and December 2019. Seventy-one patients with CSM underwent modified EOL, and 31 patients underwent traditional EOL. The primary endpoint was axial symptoms. RESULTS: Patients who underwent modified EOL had a significantly lower incidence of axial symptoms (odds ratio: 0.273; 95% confidence interval: 0.184-0.691; p = .002). The length of hospital stay (p = .263), and intraoperative blood loss (p = .402) were not significantly different between the groups. Significantly more postoperative drainage was observed in patients who underwent modified EOL (p < .001), while the cost of hospitalization in patients treated with traditional EOL was higher (p = .011). There were significant differences between modified and traditional EOL for the changes in range of motion (p < .001), modified Japanese Orthopaedic Association score (p = .001), and the Nurick grade (p = .014), while the changes of visual analogue scale (p = .250), and the neck disability index (p = .134) were not significantly different between the groups. CONCLUSION: This study found modified EOL may decrease the incidence of axial symptoms in patients with CSM compared to traditional EOL.

Adoptive transfer of immature dendritic cells with high HO-1 expression delays the onset of T1DM in NOD mice.

AIMS: To investigate the potential of imDCs with high expression of HO-1 in preventing or delaying the onset of Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. MATERIALS AND METHODS: The phenotypic features of DCs in each group were assessed using flow cytometry. Western blot analysis was used to confirm the high expression of HO-1 in imDCs induced with CoPP. Additionally, flow cytometry was used to evaluate the suppressive capacity of CoPP-induced imDCs on splenic lymphocyte proliferation. Finally, the preventive effect of CoPP-induced imDCs was tested in NOD mice. KEY FINDINGS: Compared to imDCs, CoPP-induced imDCs exhibited a reduced mean fluorescence intensity (MFI) of the co-stimulatory molecule CD80 on their surface (P < 0.05) and significantly increased HO-1 protein expression (P < 0.05). Following LPS stimulation, the MFI of co-stimulatory molecules CD80 and CD86 on the surface of CoPP-induced imDCs remained at a lower level (P < 0.05). Furthermore, there was a reduced proliferation rate of lymphocytes stimulated with anti-CD3/28 antibodies. The adoptive transfer of CoPP-imDCs significantly reduced the incidence of T1DM (16.66 % vs. control group: 66.67 %, P = 0.004). Furthermore, at 15 weeks of age, the insulitis score was also decreased in the CoPP-induced imDC treatment group (P < 0.05). There were no significant differences in serum insulin levels among all groups. SIGNIFICANCE: ImDCs induced with CoPP and exhibiting high expression of HO-1 demonstrate a robust ability to inhibit immune responses and effectively reduce the onset of diabetes in NOD mice. This finding suggests that CoPP-induced imDCs could potentially serve as a promising treatment strategy for T1DM.

ZmEREB92 plays a negative role in seed germination by regulating ethylene signaling and starch mobilization in maize.

Rapid and uniform seed germination is required for modern cropping system. Thus, it is important to optimize germination performance through breeding strategies in maize, in which identification for key regulators is needed. Here, we characterized an AP2/ERF transcription factor, ZmEREB92, as a negative regulator of seed germination in maize. Enhanced germination in ereb92 mutants is contributed by elevated ethylene signaling and starch degradation. Consistently, an ethylene signaling gene ZmEIL7 and an α-amylase gene ZmAMYa2 are identified as direct targets repressed by ZmEREB92. OsERF74, the rice ortholog of ZmEREB92, shows conserved function in negatively regulating seed germination in rice. Importantly, this orthologous gene pair is likely experienced convergently selection during maize and rice domestication. Besides, mutation of ZmEREB92 and OsERF74 both lead to enhanced germination under cold condition, suggesting their regulation on seed germination might be coupled with temperature sensitivity. Collectively, our findings uncovered the ZmEREB92-mediated regulatory mechanism of seed germination in maize and provide breeding targets for maize and rice to optimize seed germination performance towards changing climates.

A multifunctional scaffold for bone infection treatment by delivery of microRNA therapeutics combined with antimicrobial nanoparticles.

Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopaedics, made complex by antimicrobial resistance (AMR) risks due to long-term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi-faceted solution would eradicate bacterial infection without long-term antibiotic use while simultaneously stimulating osteogenesis and angiogenesis. Here, we developed a multifunctional collagen-based scaffold that addresses these needs by leveraging the potential of antibiotic-free antimicrobial nanoparticles (copper-doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA-based gene therapy (utilising an inhibitor of microRNA-138) to stimulate both osteogenesis and angiogenesis. CuBG scaffolds reduced the attachment of gram-positive bacteria by over 80%, showcasing antimicrobial functionality. The antagomiR-138 nanoparticles induced osteogenesis of human mesenchymal stem cells in vitro, and healed a large load-bearing defect in a rat femur when delivered on the scaffold. Combining both promising technologies resulted in a multifunctional antagomiR-138-activated CuBG scaffold inducing hMSC-mediated osteogenesis and stimulating vasculogenesis in an in vivo chick chorioallantoic membrane model. Overall, this multifunctional scaffold catalyses killing mechanisms in bacteria while inducing bone repair through osteogenic and angiogenic coupling, making this platform a promising multi-functional strategy for treating and repairing complex bone infections. This article is protected by copyright. All rights reserved.

In Situ Real-Time Observation of Formation and Self-Assembly of Perovskite Nanocrystals at High Temperature.

All-inorganic cesium lead halide perovskite nanocrystals (NCs) have received much attention due to their outstanding optical and electronic properties, but the underlying growth mechanism remains elusive due to their rapid formation process. Here, we report an in situ real-time study of the growth of Cs4PbBr6 NCs under practical synthesis conditions in a custom-made reactor. Through the synchrotron-based small-angle X-ray scattering technique, we find that the formation of Cs4PbBr6 NCs is accomplished in three steps: the fast nucleation process accompanied by self-focusing growth, the subsequent diffusion-limited Ostwald ripening, and the self-assembly of NCs into the face-centered cubic (fcc) superlattices at high temperature and the termination of growth. The simultaneously collected wide-angle X-ray scattering signals further corroborate the three-step growth model. The influence of superlattice formation is also elucidated, which improves the uniformity of the final NCs.

Multi-stakeholder preferences for the use of artificial intelligence in healthcare: A systematic review and thematic analysis.

INTRODUCTION: Despite the proliferation of Artificial Intelligence (AI) technology over the last decade, clinician, patient, and public perceptions of its use in healthcare raise a number of ethical, legal and social questions. We systematically review the literature on attitudes towards the use of AI in healthcare from patients, the general public and health professionals' perspectives to understand these issues from multiple perspectives. METHODOLOGY: A search for original research articles using qualitative, quantitative, and mixed methods published between 1 Jan 2001 to 24 Aug 2021 was conducted on six bibliographic databases. Data were extracted and classified into different themes representing views on: (i) knowledge and familiarity of AI, (ii) AI benefits, risks, and challenges, (iii) AI acceptability, (iv) AI development, (v) AI implementation, (vi) AI regulations, and (vii) Human - AI relationship. RESULTS: The final search identified 7,490 different records of which 105 publications were selected based on predefined inclusion/exclusion criteria. While the majority of patients, the general public and health professionals generally had a positive attitude towards the use of AI in healthcare, all groups indicated some perceived risks and challenges. Commonly perceived risks included data privacy; reduced professional autonomy; algorithmic bias; healthcare inequities; and greater burnout to acquire AI-related skills. While patients had mixed opinions on whether healthcare workers suffer from job loss due to the use of AI, health professionals strongly indicated that AI would not be able to completely replace them in their professions. Both groups shared similar doubts about AI's ability to deliver empathic care. The need for AI validation, transparency, explainability, and patient and clinical involvement in the development of AI was emphasised. To help successfully implement AI in health care, most participants envisioned that an investment in training and education campaigns was necessary, especially for health professionals. Lack of familiarity, lack of trust, and regulatory uncertainties were identified as factors hindering AI implementation. Regarding AI regulations, key themes included data access and data privacy. While the general public and patients exhibited a willingness to share anonymised data for AI development, there remained concerns about sharing data with insurance or technology companies. One key domain under this theme was the question of who should be held accountable in the case of adverse events arising from using AI. CONCLUSIONS: While overall positivity persists in attitudes and preferences toward AI use in healthcare, some prevalent problems require more attention. There is a need to go beyond addressing algorithm-related issues to look at the translation of legislation and guidelines into practice to ensure fairness, accountability, transparency, and ethics in AI.

Curcumin promotes renewal of intestinal epithelium by miR-195-3p.

ETHNOPHARMACOLOGICAL RELEVANCE: Turmeric (Curcuma longa) has been used to treat gastrointestinal disorders in the Indian Ayurvedic medical system. According to the theory behind traditional Chinese medicine, turmeric can be distributed in the spleen meridian, for which it has been used as a digestive aid. Curcumin (Cur), a natural polyphenol compound originally derived from turmeric, has anti-inflammatory activity and can assist in treating inflammatory bowel disease. AIMS OF THE STUDY: To investigate curcumin's protective effects on intestinal epithelium and explore the underlying miR-195-3p-related mechanisms. MATERIALS AND METHODS: The miR-195-3p mimics were used to over-express miR-195-3p. The in vitro effects of Cur and miR-195-3p on the intestine were shown utilizing intestinal cryptlike epithelial cell line-6 (IEC-6) cells. By fasting for 48 h, an intestinal mucosal atrophy model of SD rats was created in vivo. Cur (25 or 50 mg/kg) was assessed for its protective effect on intestinal epithelium. Glycyrrhetinic acid (GA) with an intestinal protective effect reported in our previous research was adopted as a positive drug for the in vivo and in vitro bioactivity evaluation since there is no universally positive drug for either intestinal mucosal restitution or miR-195-3p modulation. RESULTS: Cur protects the intestinal epithelium and promotes its repair after injury via down-regulating miR-195-3p. In vitro experiments showed that Cur inhibited the apoptosis of IEC-6 cells, stimulated their growth, and down-regulated the level of miR-195-3p in cells. When miR-195-3p was overexpressed, the viability of IEC-6 cells decreased while the apoptosis rate increased. All the above detrimental effects were alleviated after curcumin intervention. Moreover, Cur reversed the effect of miR-195-3p on its downstream occludin. In vivo, results showed that 48-h fasting impaired the integrity of the small intestinal mucosa (abnormal crypt structure and reduced goblet cell number), which was ameliorated by Cur treatment. In addition, the Cur treatment reversed both the increased expression level of miR-195-3p and decreased levels of ki-67 and occludin caused by fasting. CONCLUSIONS: Cur could promote the proliferation and repair after injury of the intestinal mucosa by down-regulating miR-195-3p.

KAN0438757, a novel PFKFB3 inhibitor, prevent the progression of severe acute pancreatitis via the Nrf2/HO-1 pathway in infiltrated macrophage.

Acute pancreatitis (AP) is a non-infectious pancreatic enzyme-induced disorder, a life-threatening inflammatory condition that can cause multi-organ dysfunction, characterized by high morbidity and mortality. Several therapies have been employed to target this disorder; however, few happen to be effectively employable even in the early phase. PFKFB3(6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3) is a critical regulator of glycolysis and is upregulated under inflammatory, mitogenic, and hypoxia conditions. Essential information on the targeting of the inflammatory pathway will present the termination of the disorder and recovery. Herein we investigated the protective function of KAN0438757, a potent inhibitor of PFKFB3, and its mechanism of impeding AP induced in mice. KAN0438757 was confirmed to activate the Nrf2/HO-1 inflammatory signaling pathways in response to caerulein induced acute pancreatitis (CAE-AP) and fatty acid ethyl ester induced severe acute pancreatitis (FAEE-SAP). Additionally, KAN0438757 alleviated the inflammatory process in infiltrated macrophage via the Nrf2/HO-1 inflammatory signaling pathway and demonstrated a significant effect on the growth of mice with induced AP. And more importantly, KAN0438757 displayed negligible toxicity in vivo. Taken together our data suggest KAN0438757 directly suppresses the inflammatory role of PFKFB3 and induces a protective role via the Nrf2/HO-1 pathway, which could prove as an excellent therapeutic platform for SAP amelioration.

Nutritional composition, health-promoting effects, bioavailability, and encapsulation of tree peony seed oil: a review.

Tree peony is cultivated worldwide in large quantities due to its exceptional ornamental and medicinal value. In recent years, the edible value of tree peony seed oil (TPSO) has garnered significant attention for its high content of alpha-linolenic acid (ALA, >40%) and other beneficial minor components, including phytosterols, tocopherols, squalene, and phenolics. This review provides a systematic summary of the nutritional composition and health-promoting effects of TPSO, with a specific focus on its digestion, absorption, bioavailability, and encapsulation status. Additionally, information on techniques for extracting and identifying adulteration of TPSO, as well as its commercial applications and regulated policies, is included. Thanks to its unique nutrients, TPSO offers a wide range of health benefits, such as hypolipidemic, anti-obesity, cholesterol-lowering, antioxidant and hypoglycemic activities, and regulation of the intestinal microbiota. Consequently, TPSO shows promising potential in the food and cosmetic industries and should be cultivated in more countries. However, the application of TPSO is hindered by its low bioavailability, poor stability, and limited water dispersibility. Therefore, it is crucial to develop effective delivery strategies, such as microencapsulation and emulsion, to overcome these limitations. In conclusion, this review provides a comprehensive understanding of the nutritional value of TPSO and emphasizes the need for further research on its nutrition and product development.

Male refractory hypospadias with sexual reversal: a case report.

BACKGROUND: Hypospadias is one of the most prevalent urogenital malformations in clinic. However, some hypospadias may have a more complex disorder of sex development. Usually, hypospadias in these patients is severe. Among them, the 46,XX male sex reversal syndrome is a rare disorder of sex development, and this may be the main reason for this type of hypospadias being difficult to repair. CASE PRESENTATION: We present a Han nationality 19-year-old male with failure of repeated repair of hypospadias. No sperm was found on semen analysis. Lingual mucosal graft was carried out for this patient. It still did not succeed after using lingual mucosal graft repair. Karyotype analysis of this patient confirmed 46,XX karyotype. CONCLUSION: Hypospadias with 46,XX male sex reversal syndrome is hard to repair. Chromosome karyotype examination in patients with hypospadias is suggested. Genetic testing is recommended. In the future, further research is needed on the pathogenesis of disease and how to treat and prevent it.

Predicting very early recurrence in intrahepatic cholangiocarcinoma after curative hepatectomy using machine learning radiomics based on CECT: A multi-institutional study.

BACKGROUND: Even after curative resection, the prognosis for patients with intrahepatic cholangiocarcinoma (iCCA) remains disappointing due to the extremely high incidence of postoperative recurrence. METHODS: A total of 280 iCCA patients following curative hepatectomy from three independent institutions were recruited to establish the retrospective multicenter cohort study. The very early recurrence (VER) of iCCA was defined as the appearance of recurrence within 6 months. The 3D tumor region of interest (ROI) derived from contrast-enhanced CT (CECT) was used for radiomics analysis. The independent clinical predictors for VER were histological stage, AJCC stage, and CA199 levels. We implemented K-means clustering algorithm to investigate novel radiomics-based subtypes of iCCA. Six types of machine learning (ML) algorithms were performed for VER prediction, including logistic, random forest (RF), neural network, bayes, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost). Additionally, six clinical ML (CML) models and six radiomics-clinical ML (RCML) models were developed to predict VER. Predictive performance was internally validated by 10-fold cross-validation in the training cohort, and further evaluated in the external validation cohort. RESULTS: Approximately 30 % of patients with iCCA experienced VER with extremely discouraging outcome (Hazard ratio (HR) = 5.77, 95 % Confidence Interval (CI) = 3.73-8.93, P < 0.001). Two distinct iCCA subtypes based on radiomics features were identified, and subtype 2 harbored a higher proportion of VER (47.62 % Vs 25.53 %) and significant shorter survival time than subtype 1. The average AUC values of the CML and RCML models were 0.744 ± 0.018, and 0.900 ± 0.014 in the training cohort, and 0.769 ± 0.065 and 0.929 ± 0.027 in the external validation cohort, respectively. CONCLUSION: Two radiomics-based iCCA subtypes were identified, and six RCML models were developed to predict VER of iCCA, which can be used as valid tools to guide individualized management in clinical practice.