Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To summarize the best evidence for the prevention and management of central venous catheter-related thrombosis in adults.Methods:Based on evidence-based methods, computer searches were conducted on UpToDate, BMJ Best Practice, Joanna Briggs Institute Evidence-based Healthcare Center Database in Australia, Guidelines International Network, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, Medlive, Cochrane Library, website of Infusion Nursing Society, website of Chinese Medical Association, PubMed, China Biology Medicine disc, CNKI, Wanfang database, etc. The search period was from the establishment of the database to May 31, 2022. Two researchers independently conducted literature quality evaluation and evidence level assessment.Results:A total of 12 articles were included, including 3 clinical decisions, 4 guidelines, 3 evidence summaries, 1 randomized controlled trial and 1 expert consensus. 10 topics including team and training, risk factors assessment, catheterization, functional exercise, physical prevention, drug prevention, tube flushing and sealing, observation and identification, extubation and anticoagulation, health education and 25 best evidence were summarized and formed.Conclusions:This study summarizes the best evidence currently available for the prevention and management of central venous catheter-related thrombosis in adults, so as to provide evidence-based evidence for nurses and nursing managers to scientifically manage and prevent central venous catheter-related thrombosis.

Background/Aims: Epstein-Barr virus-associated gastric cancers (EBVaGCs) have unique molecular and clinicopathological characteristics. The cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is recently recognized as the critical innate immunity against pathogens and tumors. STING is also a master regulator in the cancer-immunity cycle and targeting STING could synergize with existing immune-checkpoint therapies. However, the role of STING in GC, especially in EBVaGC, and its correlation with programmed death-ligand 1 (PD-L1) remain largely unclear. Methods: We collected 78 cases of EBVaGCs and 210 cases of EBV-negative GC (EBVnGC) from a total of 1,443 cases of GC analyzed by EBV-encoded small RNA in situ hybridization. We investigated STING and PD-L1 expression and their concomitant prognostic value in EBVaGCs and EBVnGCs using tissue microarray and immunohistochemistry. The effects of STING and PD-L1 expression on the overall survival of patients with EBVaGC or EBVnGC were assessed by univariate and multivariate analysis. Results: We found that both STING and PD-L1 exhibited significantly higher expression in the EBVaGCs than that in the EBVnGCs. The expression of STING was positively correlated with that of PD-L1 in EBVaGCs. Simultaneous negative expression of STING and PD-L1, and positive expression of STING were independent prognostic risk factors for EBVaGC and EBVnGC, respectively. Conclusions This is the first prognostic retrospective study of STING and PD-L1 expression and the prognosis among EBVaGC and EBVnGC. The expression and prognostic value of STING and PD-L1 are different in the two types of GCs. STING and PD-L1 are promising prognostic biomarkers and therapeutic targets for EBVaGC and EBVnGC.

Under the diagnosis-related groups(DRG) prospective payment system, innovative health technologies with high costs and risks may be limited to some extent. How to balance the increase of health care cost and the development of innovative health technology is a difficult problem to be solved in the current reform. By studying the relatively mature payment systems of innovative health technologies in the world, the authors found that countries generally adopted additional payment or compensation to encourage the development of new technologies. But at the same time, a relatively perfect health technology assessment and payment management mechanism had been established to ensure the standardized operation of payment plan. These international advanced experience and practice could provide references for China′s innovative health technology payment strategy under the DRG payment system. It is suggested to establish a scientific and reasonable assessment mechanism of innovative health technology, create a special access channel for innovative health technology with limited short-term evidence, and gradually form a long-term incentive mechanism of innovative health technology in DRG payment system.

The causes for male sexual orientation are complicated, which have not yet been clarified. Recent years have witnessed fruitful progress in the field of biology, while the impact of environment has received little attention. Adverse childhood experiences (ACEs), identified as a special environment in the early stage of development, can affect the individual phenotype by DNA methylation. Given the relationships among male sexual orientation, ACEs, and DNA methylation, as well as based on the existing theory, this article proposes the model "ACEs-DNA methylation-male sexual orientation"from the perspective of environment and epigenetics, aiming to provide a theoretical basis for future research.
Adverse Childhood Experiences ; Child ; DNA Methylation ; Female ; Humans ; Male ; Sexual Behavior

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.

The membrane protein claudin-3 (CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both and Of interest, CLDN3 undergoes -palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3 Moreover, the deprivation of -palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins. Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis Thus, our work reveals -palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 -palmitoylation might be a potential strategy for ovarian cancer therapy.

Objective:To explore the efficacy and safety of pretreating with oral immunosuppressants alone for ABO-incompatible (ABOi) renal transplant recipients with an initial isoagglutinin titer <1: 8.Methods:From September 2014 to October 2019, 16 cases of ABOi renal transplantation pretreated with oral immunosuppressants alone and 32 cases of ABO-compatible (ABOc) renal transplantation were recruited for comparing the inter-group incidence of graft function, acute rejection, infection and recipient and allograft survival.Results:The 16 ABOi renal transplantations were AB-to-A(n=4), AB-to-B(n=3), A-to-B(n=1), B-to-A(n=4), A-to-O(n=2) and B-to-O(n=2). The initial isoagglutinin titer (IgM & IgG) and that on the date of transplantation were both ≤1∶8. The median follow-up period was 495(90-1696) days. One patient in ABOi group underwent allograft nephrectomy due to hyperacute rejection. The graft survival rates were 93.75%(15/16) and 100%(32/32) in ABOi and ABOc groups respectively. No recipient died. No significant inter-group difference existed in postoperative renal function after 6 months (serum creatinine μmol/L: 114.30±28.13 vs. 106.08±23.80, P=0.38; eGFR ml/min/1.73 m 2: 64.93±19.60 vs. 82.34±22.58, P=0.13). In ABOi group, there were 3 episodes of postoperative infection, 2 episodes of acute rejection within 2 weeks (including 1 episode of hyperacute rejection) and 1 episode of acute rejection after 2 weeks; 5 episodes of postoperative infection, no acute rejection within 2 weeks and 5 episodes of acute rejection after 2 weeks in ABOc group. No significant inter-group difference existed in the incidence of infection or rejection ( P>0.05). Conclusions:Using oral immunosuppressant alone is both safe and feasible for ABOi renal transplantation recipients with an initial isoagglutinin titer ≤1∶8. It may greatly simplify the pretreatment scheme for those with a low initial isoagglutinin titer and lower the incidence of complications.

Objective: To investigate and analyze the actual intake of protein and energy in adult patients with severe burns during post burn days (PBDs) 3 to 14. Methods: Records of 52 adult patients with severe burns [37 males and 15 females, (37±9) years old], admitted to the Department of Plastic Surgery and Burns of Tianjin First Central Hospital from January 1st 2011 to December 31st 2017 and meeting the study inclusion criteria, were retrospectively analyzed. Nutrition intake from routes of oral diet, enteral nutrition preparations, and parenteral nutrition preparations of patients during PBDs 3 to 14 were obtained from critical care records. During PBDs 3 to 7 and PBDs 8 to 14, the personal daily total energy intake and the ratio of it to energy target of patients were calculated and compared; the personal daily intake of carbohydrate, fat, and protein and calorigenic percentages of carbohydrate, fat, and protein accounted for total energy intake, and the ratios of non-protein calories to total nitrogen of patients were calculated and compared; the personal daily energy and protein intake of patients from routes of oral diet, enteral nutrition preparations, and parenteral nutrition preparations were analyzed; the percentages of energy intake from routes of oral diet, enteral nutrition preparations, and parenteral nutrition preparations accounted for total energy intake, and the percentages of protein intake from routes of oral diet, enteral nutrition preparations, and parenteral nutrition preparations accounted for total protein intake of patients were calculated. Vomiting and diarrhea of patients during PBDs 3 to 7 and PBDs 8 to 14 were recorded. Levels of serum albumin, prealbumin, blood glucose, and triglycerides, 24-hour excretion of urinary nitrogen, nitrogen balance values of patients on PBDs 7 and 14 were recorded or calculated. Data were processed with paired t test and chi-square test. Results: (1) The personal daily total energy intake of patients during PBDs 3 to 7 and PBDs 8 to 14 were (8 696±573) and (11 980±1 259) kJ respectively, and ratios of them to energy target [(13 290±1 561) kJ] were 65.4% and 90.1% respectively. The personal daily total energy intake of patients during PBDs 3 to 7 was obviously lower than that during PBDs 8 to 14 (t=18.172, P<0.01). (2) The personal daily intake of carbohydrate, fat, and protein of patients during PBDs 8 to 14 were obviously higher than those during PBDs 3 to 7 (t=15.628, 22.231, 10.403, P<0.01). The personal daily calorigenic percentages of carbohydrate, fat, and protein accounted for total energy intake of patients were 56.8%, 25.1%, and 18.3% respectively during PBDs 3 to 7 and 54.2%, 27.0%, and 18.7% respectively during PBDs 8 to 14. The calorigenic constituent ratio of personal daily intake of carbohydrate, fat, and protein accounted for total energy intake of patients during PBDs 3 to 7 was close to that during PBDs 8 to 14 (χ²=0.185, P>0.05). The ratios of non-protein calories to total nitrogen (kJ∶g) of patients during PBDs 3 to 7 and PBDs 8 to 14 were 469∶ 1 and 456∶ 1 respectively. (3) The personal daily energy intake of patients from routes of oral diet and parenteral nutrition preparations during PBDs 8 to 14 [(4 394±978), (5 723±898) kJ] were obviously higher than those during PBDs 3 to 7 [(2 137±453), (4 855±825) kJ, t=26.516, 6.583, P<0.01], while the personal daily energy intake of patients from routes of enteral nutrition preparations during PBDs 8 to 14 was close to that during PBDs 3 to 7 (t=1.922, P>0.05). The constituent ratio of personal daily energy during PBDs 3 to 7 was close to that during PBDs 8 to 14 (χ²=4.100, P>0.05). The personal daily protein intake of patients from route of oral diet during PBDs 8 to 14 was (58±22) g, obviously higher than (25±6) g during PBDs 3 to 7 (t=14.514, P<0.01). The personal daily protein intake of patients from routes of enteral nutrition preparations and parenteral nutrition preparations during PBDs 8 to 14 was close to those during PBDs 3 to 7 (t=1.924, 1.110, P>0.05). The constituent ratio of personal daily protein intake from routes of oral diet, enteral nutrition preparations, and parenteral nutrition preparations accounted for total protein intake during PBDs 8 to 14 was close to that during PBDs 3 to 7 (χ²=5.634, P>0.05). (4) There were 3 patients with vomiting and 4 patients with diarrhea during PBDs 3 to 7, and 1 patient experienced both of them during PBDs 8 to 14. The levels of serum albumin, prealbumin, blood glucose, and triglycerides, 24-hour excretion of urinary nitrogen, and nitrogen balance values of patients on PBDs 7 and 14 were (29±4) and (30±4) g/L, (132±42) and (171±48) mg/L, (7.4±2.8) and (6.7±2.8) mmol/L, (1.5±0.7) and (1.4±0.7) mmol/L, (30.5±4.3) and (34.5±2.2) g, -(25.1±2.6) and -(23.7±3.9) g, respectively. Conclusions The personal daily total energy intake of patients during PBDs 3 to 7 was lower than that during PBDs 8 to 14. The calorigenic constituent ratio of personal daily intake of carbohydrate, fat, and protein accounted for total energy of patients during PBDs 3 to 7 was close to that during PBDs 8 to 14. Energy and protein intake were mostly derived from parenteral nutrition preparations during PBDs 3 to 7, while those during PBDs 8 to 14 were mainly derived from parenteral nutrition preparations and oral diet.