ObjectiveTo investigate the effects and potential mechanisms of morning and evening fasting on postprandial lipid responses, a post hoc analysis based on a crossover randomized controlled trial was conducted to assess the effects of different fasting strategies on postprandial lipid metabolism in community residents in Shanghai. MethodsA total of 23 participants took part in a randomized crossover trial involving two intervention days: morning fasting and evening fasting, with a washout period of 6 days between intervention days. Two-way analysis of variance was used to test the differences in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the relative expression of circadian clock genes before and after the next meal under fasting. Wilcoxon rank sum tests were used to analyze the different metabolites between the two groups. Principal component analysis and Orthogonal partial least squares-discriminant analysis were conducted to evaluate the ability of metabolites to differentiate between morning fasting and evening fasting and identify the important differential metabolites. After adjusting for age, sex, and BMI, a partial correlation analysis was performed to identify metabolites associated with plasma lipids. In addition, important metabolites associated with plasma lipids were computed by pathway enrichment analysis. ResultsAfter evening fasting intervention, fasting TG level [(0.37±0.29) vs (0.27±0.18)] mmol·L^-1, fasting and postprandial change values in TC [(2.74±0.47) vs (2.51±0.27)] mmol·L^-1 and LDL-C [(1.32±0.38) vs (0.99±0.27)] mmol·L^-1 were significantly lower than those after morning fasting (P<0.05). While, change values of fasting LDL-C [(0.89±0.37) vs (1.14±0.37)] mmol·L^-1 and TG [(1.14±0.19) vs (1.28±0.17)] mmol·L^-1 were significantly higher than those after morning fasting intervention (P<0.05). After fasting intervention, the relative expression of AMPK, CRY1, CLOCK, MTNR1B, AANAT, and ASMT was correlated with the amount of plasma lipid changes (P<0.05). Specifically, CLOCK and AANAT were upregulated following evening fasting and downregulated after morning fasting. Among the 217 important differential metabolites, 111 were correlated with plasma lipids, and which were primarily enriched in the cysteine and methionine metabolism pathways (P<0.05). ConclusionCompared to morning fasting, evening fasting was more effective in improving postprandial lipid responses, indicating that an evening fasting window during intermittent fasting could be conducive to cardiovascular disease prevention in adults. Meanwhile, it is suggested that morning and evening fasting may affect lipid responses through circadian rhythm oscillations and the cysteine and methionine metabolism pathways.

Acute-on-chronic liver failure (ACLF) is an acute deterioration of liver function occurring on the basis of chronic liver disease, accompanied by failure of the liver and extrahepatic organs, and is associated with a high short-term mortality rate. Liver transplantation is the only curative treatment for patients with ACLF. However, the shortage of donor livers and limitations of the organ allocation system mean that only a minority of patients can receive transplants. The current organ allocation system based on the model for end-stage liver disease (MELD) score may underestimate the urgency of liver transplantation for ACLF patients. Therefore, it is urgent to develop better assessment tools to determine which ACLF patients are most likely to benefit from liver transplantation. This article reviews the current mainstream definitions of ACLF, the selection of candidates for liver transplantation in ACLF, and the prognostic scoring systems for liver transplantation in ACLF, both domestically and internationally, in order to provide a reference for the prognostic assessment of liver transplantation in ACLF patients.

"Stagnation" is an important pathological state in the development and progression of malignant tumors. However， its intrinsic connection with different stages of tumor evolution has not been clearly elucidated in previous studies. Drawing on clinical practice， this paper proposes the theory of stagnant toxin， emphasizing stage-specific pathogenesis and differentiated treatment strategies for tumors based on the varying manifestations of stagnation at each phase. The theory interprets the pathogenesis of stagnant toxin across the stages of tumor development through the five elements "wood， fire， earth， metal， and water" corresponding respectively to wood stagnation in the precancerous stage， metal stagnation in the postoperative phase， fire stagnation during adjuvant therapy， earth stagnation in the progressive stage， and water stagnation in the advanced stage. Each type of stagnation reflects a distinct pathogenic mechanism， such as wood stagnation giving rise to disease， metal stagnation inducing residual symptoms， fire stagnation resulting in ulceration， earth stagnation spreading toxin transmission， and water stagnation leading to critical deterioration. Accordingly， the treatment principles include guiding wood stagnation with counterflow， dispersing metal stagnation to harmonize symptoms， venting fire stagnation to regress ulcers， depleting earth stagnation to block progression， and controlling water stagnation to preserve vitality. This theoretical framework offers a traditional Chinese medicine perspective for understanding and treating malignant tumors based on the concept of stagnant toxin.

Objective: To analyze the association between each regional fat mass and total body bone mineral density (BMD) in children and adolescents aged 7-17 years in Beijing, so as to provide theoretical basis and practical guidance for implementing interventions. Methods: From September to December 2020, a stratified cluster random sampling method was used to select 1 423 children and adolescents aged 7-17 years in Tongzhou District, Beijing. Dual energy X-ray absorptiometry (DXA) was employed to measure regional body composition and total body BMD. Multiple linear regression was used to analyze the association between regional fat mass and total body BMD. Results: The median (interquartile range) fat mass values for total body, upper limbs, abdomen, hips, and thighs were 13.51(8.84, 19.21), 1.59(1.08, 2.23), 0.73(0.39, 1.29), 2.32(1.46, 3.26), 5.29(3.59, 7.21)kg, respectively. After adjusting for covariates, the results of multiple linear regression analysis showed that total body fat mass (β=0.010), abdominal fat mass (β=-0.100), and hip fat mass (β=0.104) were significant associations with total body BMD (all P<0.01). Sexstratified analysis revealed that in boys, total body fat mass (β=0.008) and hip fat mass (β=0.058) were positively associated with BMD, while thigh fat mass (β=-0.038) showed a negative association with total body BMD (all P<0.05). In girls, total body fat mass (β=0.013), hip fat mass (β=0.163), and thigh fat mass (β=0.023) were positively associated with total body BMD, whereas abdominal fat mass (β=-0.196) showed a negative association with total body BMD (all P<0.05). Among children and adolescents with body fat percentage below the standard range, within the standard range and above the standard range, total body fat masses were positively associated with total body BMD (β=0.021, 0.016, 0.015); among children and adolescents with body fat percentage within the standard range while upper limb (β=-0.042), abdominal (β=-0.067), and thigh fat mass (β=-0.018) showed negative associations with total body BMD, and hip fat mass demonstrated a positive association with total body BMD (β=0.082) (all P<0.05). Conclusion Regional fat distribution is associated with total body BMD in children and adolescents, with the nature of these associations varying by sex and body fat percentage.

Lung cancer （LC） is a significant global public health issue， with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually， posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However， postoperative multidimensional functional impairments， including respiratory， mucosal， and psychological functions， are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration， but also negatively correlate with prognosis， facilitating disease recurrence and metastasis. At present， postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine （TCM） differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery， and guided by the classical TCM theory of "lungs governing Qi"， this study， based on the core concept of the "five perspectives on treatment" theory， innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase， mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase， and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly， stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase， the strategy emphasizes tonifying Qi and uplifting sinking Qi， with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase， the approach focuses on nourishing Yin and uplifting Qi， with prescription combinations that integrate unblocking and tonification. In the consolidation phase， the strategy aims to resolve constraint and uplift Qi， with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation， clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM， offering a new approach for TCM differentiation and treatment in the full-cycle， stage-based， and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.

Tumor treatment-related adverse reactions are a major focus of clinical concern， among which recurrent aphthous oral ulcers （RAU） associated with targeted therapy for lung cancer （LC） are among the most painful and distressing for patients. Currently， modern medical interventions show limited efficacy， and there is an urgent need for more effective treatment strategies. This study differentiates RAU associated with targeted therapy for LC from chemotherapy-related and ordinary oral ulcers， elucidates the pathophysiological basis of such ulcers， and traces the theoretical origin of "Yin deficiency and Qi collapse". Based on the new system of "five perspectives on diagnosis and treatment" for tumor prevention and treatment， with a focus on the core and symptom perspectives and rooted in the traditional concept of "lung dominating Qi"， we innovatively propose the concept of "medicine-induced ulcer" and are the first to introduce the theory of "Yin deficiency and Qi collapse" into the syndrome differentiation and treatment of RAU associated with targeted therapy for LC （i.e.， medicine-induced ulcer）. We propose that "Yin deficiency and Qi collapse" is the core pathogenesis of medicine-induced ulcers， in which the collapse of formless Qi is the key to their onset， while the deficiency and stasis of tangible Yin and blood constitute the root of recurrence. A hierarchical strategy for syndrome differentiation and treatment is established： first treating the collapse of formless Qi， then replenishing tangible deficiencies， and concurrently preventing recurrence. We emphasize that treatment should address both root and manifestation， with appropriate prioritization. In the acute phase， while relieving symptoms and promoting ulcer healing by nourishing Qi， uplifting collapse， and generating body fluids， attention should also be paid to nourishing spleen Yin， facilitating the circulation of nutritive Qi， and alleviating stasis to target the root pathogenesis and reduce recurrence. A verified case is presented to support this approach. This study enriches the theoretical framework and clinical methods of traditional Chinese medicine （TCM） in the treatment of RAU associated with targeted therapy for LC， promotes symptom management of treatment-related adverse reactions through integrated TCM and Western medicine， and provides theoretical support for the construction and development of a comprehensive differentiation and treatment system for lung cancer prevention， treatment， and rehabilitation.

L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

Objective:To explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders (NDDs) due to variants of TANC2 gene. Methods:Clinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. By using " TANC2 gene", "Neurodevelopmental disorders", "Nervous system development disorders", " TANC2" as the key words, similar cases were searched from the CNKI, Wanfang database platform and PubMed database, with the search time set as from the establishment of the database to December 2023. This study was approved by Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No. 2020-57). Results:Case 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures. Her epilepsy had resolved with the treatment of oxcarbazepine, which was stopped at the age of 2-year-and-7-month. Her language, movement and intelligence development were all normal. Case 2 was a 1-year-and-10-month-old boy, who had developed convulsions at 1 year old. His seizure type was myoclonus, and the frequency was dozens of times a day. His epilepsy had resolved with the treatment of sodium valproate. His language, movement and intelligence development was delayed for about half a year. Genetic analysis showed that both children had harbored novel variants of the TANC2 gene (NM_025185.4), including c. 3398G>A (p.Gly1133Glu) and c.2829+ 1G>A, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the former was rated as likely pathogenic (PS2+ PM2_Supporting+ PP3) and the latter was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Two previous reports were retrieved, which had involved 17 cases and 16 variants. Common features had included autism spectrum disorder (70.6%, 12/17), intellectual disability (94.1%, 16/17), language and motor retardation (88.2%, 15/17; 58.8%, 10/17), facial dysmorphism, epilepsy, ataxia, and thoracic and spinal deformities. Conclusion:Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.