A dual-function selection system enables positive selection of multigene CRISPR mutants and negative selection of Cas9-free progeny in Arabidopsis.

The CRISPR/Cas9 technology revolutionizes targeted gene knockout in diverse organisms including plants. However, screening edited alleles, particularly those with multiplex editing, from herbicide- or antibiotic-resistant transgenic plants and segregating out the Cas9 transgene represent two laborious processes. Current solutions to facilitate these processes rely on different selection markers. Here, by taking advantage of the opposite functions of a d-amino acid oxidase (DAO) in detoxifying d-serine and in metabolizing non-toxic d-valine to a cytotoxic product, we develop a DAO-based selection system that simultaneously enables the enrichment of multigene edited alleles and elimination of Cas9-containing progeny in Arabidopsis thaliana. Among five DAOs tested in Escherichia coli, the one encoded by Trigonopsis variabilis (TvDAO) could confer slightly stronger d-serine resistance than other homologs. Transgenic expression of TvDAO in Arabidopsis allowed a clear distinction between transgenic and non-transgenic plants in both d-serine-conditioned positive selection and d-valine-conditioned negative selection. As a proof of concept, we combined CRISPR-induced single-strand annealing repair of a dead TvDAO with d-serine-based positive selection to help identify transgenic plants with multiplex editing, where d-serine-resistant plants exhibited considerably higher co-editing frequencies at three endogenous target genes than those selected by hygromycin. Subsequently, d-valine-based negative selection successfully removed Cas9 and TvDAO transgenes from the survival offspring carrying inherited mutations. Collectively, this work provides a novel strategy to ease CRISPR mutant identification and Cas9 transgene elimination using a single selection marker, which promises more efficient and simplified multiplex CRISPR editing in plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00132-6.

Advances in biotin biosynthesis and biotechnological production in microorganisms.

Biotin, also known as vitamin H or B7, acts as a crucial cofactor in the central metabolism processes of fatty acids, amino acids, and carbohydrates. Biotin has important applications in food additives, biomedicine, and other fields. While the ability to synthesize biotin de novo is confined to microorganisms and plants, humans and animals require substantial daily intake, primarily through dietary sources and intestinal microflora. Currently, chemical synthesis stands as the primary method for commercial biotin production, although microbial biotin production offers an environmentally sustainable alternative with promising prospects. This review presents a comprehensive overview of the pathways involved in de novo biotin synthesis in various species of microbes and insights into its regulatory and transport systems. Furthermore, diverse strategies are discussed to improve the biotin production here, including mutation breeding, rational metabolic engineering design, artificial genetic modification, and process optimization. The review also presents the potential strategies for addressing current challenges for industrial-scale bioproduction of biotin in the future. This review is very helpful for exploring efficient and sustainable strategies for large-scale biotin production.

An adaptive algorithm for acoustic feedback compensation and secondary path identification of an active noise control system.

An adaptive variable step-size algorithm is proposed in this paper to address the impact of the real-time acoustic feedback and the real-time secondary path identification on the overall noise reduction performance of an active noise control system. An automated adjustment weight factor is introduced in the algorithm to accelerate the convergence of the acoustic feedback path as well as the secondary path identification, and to prevent possible system divergence. It is shown in this study that the proposed algorithm can resolve the trade-off between a fast convergence and a low misalignment of the virtual and the actual control paths typically found in conventional algorithms. An optimized control structure is also proposed in the study by enabling an adaptive gain adjustment based on the output of the auxiliary filter to enhance the practicality of the control system. The effectiveness of the algorithm is tested using two simulated multi-component signals and a broadband noise signal, and the results confirm that the proposed algorithm can achieve a good noise reduction with only a few iterations.

Bidirectional Relationship Between Circadian Rhythm and Frailty.

Coupled with the ageing population, frailty, characterized by high prevalence and difficult treatment, has progressively evolved into a significant public health concern. Frail individuals can often observe serious metabolic disorders and sleep-wake cycle disruption, which may be caused by the decline in physiological reserve and increased vulnerability. Moreover, sleep-wake cycle disruptions and metabolic dysfunctions associated with circadian rhythm disorders are considered to be a central part of the disorder. Previous studies have documented a correlation between frailty and sleep-wake disruptions; nevertheless, the association between circadian rhythm disorders and frailty has not yet been definitively established. Hence, we hypothesize a bidirectional link between circadian rhythm disorders and frailty, with each condition exerting a significant influence on the progression of the other's disease trajectory.

Hidden prevalence of deletion-inversion bi-alleles in CRISPR-mediated deletions of tandemly arrayed genes in plants.

Tandemly arrayed genes (TAGs) with functional redundancy and chromosomal linkage constitute 14 ~ 35% in sequenced plant genomes. The multiplex CRISPR system is the tool of choice for creating targeted TAG deletions. Here, we show that up to ~80% of CRISPR-mediated TAG knockout alleles in Arabidopsis and rice are deletion-inversion (delinver) bi-alleles, which are easily misidentified as homozygous deletion alleles by routine PCR-based genotyping. This can lead to misinterpretation of experimental data and production of progenies with genetic heterogeneity in an unnoticed manner. In ~2,650 transgenic events, delinver mutation frequencies are predominantly correlated with deletion frequencies but unrelated to chromosomal locations or deletion sizes. Delinver mutations also occur frequently at genomic non-TAG loci during multiplexed CRISPR editing. Our work raises the alarm about delinver mutations as common unwanted products of targeted TAG deletions in plants and helps prevent false interpretation of plant TAG functions due to this hidden genotype issue.

WeiTsing: a new face of Ca2+-permeable channels in plant immunity.

Plants employ pattern- and effector-triggered immunity (PTI and ETI) to synergistically defend invading pathogens and insect herbivores. Both PTI and ETI can induce cytosolic Ca2+ spikes, despite in different spatiotemporal patterns, to activate downstream Ca2+-dependent immune signaling cascades. While multiple families of Ca2+-permeable channels at the plasma membrane have been uncovered, the counterparts responsible for Ca2+ release from intracellular stores remain poorly understood. In a groundbreaking paper published recently by Cell, the authors reported that WeiTsing, an Arabidopsis endoplasmic reticulum (ER)-resident protein that was specifically expressed in the pericycle upon Plasmodiophora brassicae (Pb) infection, could form resistosome-like Ca2+-conducting channel and protect the stele of Brassica crops from Pb colonization. As the channel activity of WeiTsing was indispensable for its immune function, the findings highlight a previously underappreciated role of Ca2+ release from intracellular repertoire in promoting plant disease resistance.

Immunogenicity and safety of an Escherichia coli-produced human papillomavirus (types 6/11/16/18/31/33/45/52/58) L1 virus-like-particle vaccine: a phase 2 double-blind, randomized, controlled trial.

The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations.

Head-to-head immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil 9 in women aged 18-26 years in China: a randomised blinded clinical trial.

BACKGROUND: An Escherichia coli-produced human papillomavirus (HPV) 16 and 18 bivalent vaccine (Cecolin) was prequalified by WHO in 2021. This study aimed to compare the immunogenicity of the E coli-produced HPV 9-valent vaccine Cecolin 9 (against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) with Gardasil 9. METHODS: This was a randomised, single-blind trial conducted in China. Healthy non-pregnant women aged 18-26 years, who were not breastfeeding and with no HPV vaccination history, were enrolled in the Ganyu Centre for Disease Control and Prevention (Lianyungang City, Jiangsu Province, China). Women were stratified by age (18-22 years and 23-26 years) and randomly assigned (1:1) using a permutated block size of eight to receive three doses of Cecolin 9 or Gardasil 9 at day 0, day 45, and month 6. All participants, as well as study personnel without access to the vaccines, were masked. Neutralising antibodies were measured by a triple-colour pseudovirion-based neutralisation assay. The primary outcomes, seroconversion rates and geometric mean concentrations (GMCs) at month 7, were analysed in the per-protocol set for immunogenicity (PPS-I). Non-inferiority was identified for the lower limit of the 95% CI of the GMC ratio (Cecolin 9 vs Gardasil 9) at a margin of 0·5 and a seroconversion rate difference (Cecolin 9-Gardasil 9) at a margin of -5%. This study was registered at ClinicalTrials.gov (NCT04782895) and is completed. FINDINGS: From March 14 to 18, 2021, a total of 553 potential participants were screened, of which 244 received at least one dose of Cecolin 9 and 243 received at least one dose of Gardasil 9. The seroconversion rates for all HPV types in both groups were 100% in the PPS-I, with the values of the lower limits of 95% CIs for seroconversion rate differences ranging between -1·8% and -1·7%. The GMC ratios of five types were higher than 1·0, with the highest ratio, for HPV 58, at 1·65 (95% CI 1·38-1·97), and those of four types were lower than 1·0, with the lowest ratio, for HPV 11, at 0·79 (0·68-0·93). The incidence of adverse reactions in both groups was similar (43% [104/244] vs 47% [115/243]). INTERPRETATION: Cecolin 9 induced non-inferior HPV type-specific immune responses compared with Gardasil 9 and is a potential candidate to accelerate the elimination of cervical cancer by allowing for global accessibility to 9-valent HPV vaccinations, especially in low-income and middle-income countries. FUNDING: National Natural Science Foundation, Fujian Provincial Natural Science Foundation, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax.

Comparing artificial intelligence to humans for endoscopic diagnosis of gastric neoplasia: An external validation study.

OBJECTIVES: Artificial intelligence (AI) uses deep learning functionalities that may enhance the detection of early gastric cancer during endoscopy. An AI-based endoscopic system for upper endoscopy was recently developed in Japan. We aim to validate this AI-based system in a Singaporean cohort. METHODS: There were 300 de-identified still images prepared from endoscopy video files obtained from subjects that underwent gastroscopy in National University Hospital (NUH). Five specialists and 6 non-specialists (trainees) from NUH were assigned to read and categorize the images into "neoplastic" or "non-neoplastic." Results were then compared with the readings performed by the endoscopic AI system. RESULTS: The mean accuracy, sensitivity, and specificity for the 11 endoscopists were 0.847, 0.525, and 0.872, respectively. These values for the AI-based system were 0.777, 0.591, and 0.791, respectively. While AI in general did not perform better than endoscopists on the whole, in the subgroup of high-grade dysplastic lesions, only 29.1% were picked up by the endoscopist rating, but 80% were classified as neoplastic by AI (P = 0.0011). The average diagnostic time was also faster in AI compared with endoscopists (677.1 s vs 42.02 s (P < 0.001). CONCLUSION: We demonstrated that an AI system developed in another health system was comparable in diagnostic accuracy in the evaluation of static images. AI systems are faster and not fatigable and may have a role in augmenting human diagnosis during endoscopy. With more advances in AI and larger studies to support its efficacy it would likely play a larger role in screening endoscopy in future.

Safety and immunogenicity of an Escherichia coli-produced 9-valent human papillomavirus L1 virus-like particle vaccine (types 6/11/16/18/31/33/45/52/58) in healthy adults: an open-label, dose-escalation phase 1 clinical trial.

Background: A safe and highly efficacious Escherichia coli (E. coli)-produced HPV 16/18 bivalent vaccine has been prequalified by the World Health Organization. Here, we conducted a single-center, open-label, dose-escalation phase 1 clinical trial to evaluate the safety and immunogenicity of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. Method: Twenty-four eligible volunteers aged 18-45 years were enrolled in January 2019 in Dongtai, China and received 0.5 mL (135 µg) or 1.0 mL (270 µg) of the candidate vaccine with a 0/1/6-month dose-escalation schedule. Local and systemic adverse events (AEs) occurring within 30 days after each vaccination and serious adverse events (SAEs) occurring within 7 months were recorded. Blood samples from each participant were collected before and 2 days after the first and third vaccinations to determine changes in laboratory parameters. Serum IgG and neutralizing antibody (nAb) levels against each HPV type at month 7 were analyzed (ClinicalTrials.gov: NCT03813940). Findings: The incidences of total AEs in the 135 µg and 270 µg groups were 66.7% and 83.3%, respectively. All AEs were mild or moderate, and no SAEs were reported. No clinically significant changes were found in paired blood indices before or after any of the vaccinations. All the participants in the per-protocol set except for two who failed to seroconvert for HPV 11 or 58 in the 135 µg group seroconverted at month 7 for both IgG and nAbs. Interpretation: The candidate E. coli-produced 9vHPV vaccine has been preliminarily proven to be well tolerated and immunogenic, which encourages further studies in large cohorts with a wider age range. Funding: This study was supported by the National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Fujian Province Health and Education Joint Research Program, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax Biotechnology Co., Ltd.

Poaceae-specific ß-1,3;1,4-d-glucans link jasmonate signalling to OsLecRK1-mediated defence response during rice-brown planthopper interactions.

Brown planthopper (BPH, Nilaparvata lugens), a highly destructive insect pest, poses a serious threat to rice (Oryza sativa) production worldwide. Jasmonates are key phytohormones that regulate plant defences against BPH; however, the molecular link between jasmonates and BPH responses in rice remains largely unknown. Here, we discovered a Poaceae-specific metabolite, mixed-linkage ß-1,3;1,4-d-glucan (MLG), which contributes to jasmonate-mediated BPH resistance. MLG levels in rice significantly increased upon BPH attack. Overexpressing OsCslF6, which encodes a glucan synthase that catalyses MLG biosynthesis, significantly enhanced BPH resistance and cell wall thickness in vascular bundles, whereas knockout of OsCslF6 reduced BPH resistance and vascular wall thickness. OsMYC2, a master transcription factor of jasmonate signalling, directly controlled the upregulation of OsCslF6 in response to BPH feeding. The AT-rich domain of the OsCslF6 promoter varies in rice varieties from different locations and natural variants in this domain were associated with BPH resistance. MLG-derived oligosaccharides bound to the plasma membrane-anchored LECTIN RECEPTOR KINASE1 OsLecRK1 and modulated its activity. Thus, our findings suggest that the OsMYC2-OsCslF6 module regulates pest resistance by modulating MLG production to enhance vascular wall thickness and OsLecRK1-mediated defence signalling during rice-BPH interactions.

Microfluidic rotating-target device capable of three-degrees-of-freedom motion for efficient in situ serial synchrotron crystallography.

There is an increasing demand for simple and efficient sample delivery technology to match the rapid development of serial crystallography and its wide application in analyzing the structural dynamics of biological macromolecules. Here, a microfluidic rotating-target device is presented, capable of three-degrees-of-freedom motion, including two rotational degrees of freedom and one translational degree of freedom, for sample delivery. Lysozyme crystals were used as a test model with this device to collect serial synchrotron crystallography data and the device was found to be convenient and useful. This device enables in situ diffraction from crystals in a microfluidic channel without the need for crystal harvesting. The circular motion ensures that the delivery speed can be adjusted over a wide range, showing its good compatibility with different light sources. Moreover, the three-degrees-of-freedom motion guarantees the full utilization of crystals. Hence, sample consumption is greatly reduced, and only 0.1 mg of protein is consumed in collecting a complete dataset.

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Chilo suppressalis heat shock proteins are regulated by heat shock factor 1 during heat stress.

Heat shock factor 1 (HSF1) functions to maintain cellular and organismal homeostasis by regulating the expression of target genes, including those encoding heat shock proteins (HSPs). In the present study, the gene encoding HSF1 was cloned from the rice pest Chilo suppressalis, and designated Cshsf1. The deduced protein product, CsHSF1, contained conserved domains typical of the HSF1 family, including a DNA-binding domain, two hydrophobic heptad repeat domains, and a C-terminal transactivation domain. Real-time quantitative PCR showed that Cshsf1 was highly expressed in hemocytes. Expression analysis in different developmental stages of C. suppressalis revealed that Cshsf1 was most highly expressed in male adults. RNAi-mediated silencing of Cshsf1 expression reduced C. suppressalis survival at high temperatures. To investigate the regulatory interactions between Cshsf1 and Cshsps, the promoters and expression patterns of 18 identified Cshsps in C. suppressalis were analysed; four types of heat shock elements (HSEs) were identified in promoter regions including canonical, tail-tail, head-head, and step/gap. The expression of Cshsp19.0, Cshsp21.7B, Cshsp60, Cshsp70 and Cshsp90 was positively regulated by Cshsf1; however, Cshsp22.8, Cshsp702, Cshsp705 and Cshsp706 gene expression was not altered. This study provides a foundation for future studies of HSF1 in insects during thermal stress.

Application of intermittent flap opening in L-shaped surgical incision of calcaneal fracture / 中国骨伤

OBJECTIVE@#To explore clinical effect of intermittent flap opening technique in L-shaped incision of calcaneal fracture.@*METHODS@#From January 2017 to January 2019, 48 patients with Sanders typeⅡ to Ⅳ calcaneal fractures were treated by open reduction and internal fixation. According to different flap opening techniques, the patients were divided into control group and observation group, 24 patients in each group. In observation group, there were 17 males and 7 females, aged from 20 to 60 years old with an average of(45.12±9.56) years old;7 patients were typeⅡ, 10 patients were type Ⅲ and 7 patients were type Ⅳ according to Sanders classification;3 patients were C0, 16 patients were C1 and 5 patients were C2 according to Tscherne-Gotzen soft-tissue assessment;treated with intermittent flap technique. In control group, there were 19 males and 5 females aged from 20 to 60 years old with an average of (47.32±10.67) years old;7 patients were typeⅡ, 11 patients were type Ⅲ and 6 patients were type Ⅳ according to Sanders classification;2 patients were C0, 18 patients were C1 and 4 patients were C2 according to Tschemc-Gotzen soft-tissue assessment;treated with static flap opening technique. Operation time, flap retraction time, changes of Böhler angle and Gissane angle before and after operation at 3 days, and occurrence of incision complications were observed and compared between two groups.@*RESULTS@#All patients were followed up from 3 to 6 months with an average of(4.52±1.01) months. There were no significant differences in operation time, changes of Böhler angle and Gissane angle before and after operation at 3 days between the two groups(P>0.05);there was statistical difference in flap retraction time between two groups(P<0.05). Occurrence of incision complications in observation group was significantly lower than that in control group (P<0.05).@*CONCLUSION@#Intermittent flap opening technique is superior to static opening technique in reducing incision complications of lateral "L" approach of calcaneus. Single Kirschner wire opening does not affect the exposure, reduction and fixation of fracture during operation.

Study on the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng / 中国针灸

To explore the methods of the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng. The medical case records data of Jiusheng was collected, the frequency statistic was analyzed based on Python3.8.6, complex network analysis was performed using Gephi9.2 software, community analysis was performed by the ancient and modern medical case cloud platform V2.3.5, and analysis and verification of correlation graph and weight graph were proceed by Neo4j3.5.25 image database. The disease systems with frequency≥10 % were surgery, ophthalmology and otorhinolaryngology, locomotor, digestive and respiratory systems. The diseases under the disease system were mainly carbuncle, arthritis, lumbar disc herniation and headache. The commonly used moxibustion methods were fumigating moxibustion, blowing moxibustion, direct moxibustion and warming acupuncture. The core prescription of points obtained by complex network analysis included Yatong point, Zhiyang(GV 9), Sanyinjiao(SP 6), Dazhui(GV 14), Zusanli(ST 36), Lingtai(GV 10), Xinshu(BL 15), Zhijian point and Hegu(LI 4), which were basically consistent with high-frequency points. A total of 6 communities were obtained by community analysis, corresponding to different diseases. Through the analysis of correlation graph, 13 pairs of strong association rule points were obtained. The correlation between Zhiyang(GV 9)-Dazhui(GV 14) and Yatong point-Lingtai(GV 10) was the strongest. The acupoints with high correlation with Yatong point were Zhiyang(GV 9), Lingtai(GV 10), Dazhui(GV 14), Zusanli(ST 36) and Sanyinjiao(SP 6). In the weight graph of the high-frequency disease system, the relationship of the first weight of the surgery system disease was fumigating moxibustion-carbuncle-Yatong point, and the relationship of the first weight of the ophthalmology and otorhinolaryngology system disease was blowing moxibustion-laryngitis-Hegu (LI 4). The results of correlation graph and weight graph are consistent with the results of data mining, which can be used as an effective way to study the knowledge base of moxibustion diagnosis and treatment in the future.

Prognostic value of serum cystatin C in patients with congenital heart disease-associated pulmonary arterial hypertension / 中国胸心血管外科临床杂志

@#Objective    To explore the prognostic value of serum cystatin C (Cys C) in patients with congenital heart disease-associated pulmonary arterial hypertension (PAH-CHD). Methods    A retrospective cohort study was conducted on adult PAH-CHD patients who were hospitalized for the first time in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to January 2020. The serum Cys C and other related data of patients were collected. The median follow-up time was 57 months. The main end event was all-cause death. According to the prognosis, the patients were divided into a survival group and a death group. Cox regression was used to analyze the risk factors for all-cause death in patients with PAH-CHD. Results    A total of 456 patients were enrolled, including 160 males and 296 females, aged 38.99±14.72 years. The baseline data showed that there were statistical differences in resting heart rate, serum Cys C, creatinine, NT-proB-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity C reactive protein (hs-CRP), New York Heart Association (NYHA) cardiac function classification and serum potassium between the survival group and the death group. Univariate Cox regression analysis showed that serum  Cys C, NT-proBNP, hs-cTnT, creatinine and NYHA cardiac function classification were related risk factors for all-cause death in patients with PAH-CHD. Multivariate Cox regression analysis showed that serum Cys C (HR=3.820, 95%CI 2.053-7.108, P<0.001), NYHA grade Ⅲ (HR=2.234, 95%CI 1.316-3.521, P=0.010), NYHA grade Ⅳ (HR=4.037, 95%CI 1.899-7.810, P=0.002) and NT-proBNP (HR=1.026, 95%CI 1.013-1.039, P<0.001) were independent risk factors for all-cause death in patients with PAH-CHD and had a good predictive value. Conclusion    As a new cardiac marker, serum Cys C can predict all-cause death in patients with PAH-CHD and is an independent risk factor.

Searching for potential biomarkers reflecting early injury and progressive of podocytes in nephropathy based on cellular metabolomics combined with ROC analysis / 药学学报

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Application of nursing management based on self-efficacy theory in the patients of early functional exercise of the affected limb after permanent pacemaker implantation / 中国实用护理杂志

Objective:To study the application value of nursing management based on self-efficacy theory in the early functional exercise of the affected limb after permanent pacemaker implantation.Methods:This study was a randomized controlled trial. A total of 90 patients who underwent permanent pacemaker implantation in Wuxi Second People′s Hospital (the Affiliated Central Hospital of Jiangnan University) from May 2019 to March 2021 were enrolled. They were divided into observation group and control group with 45 patients each according to random number table. The control group received routine nursing intervention, and the observation group received supplemental management interventions based on self-efficacy theory. The rate of post-operative rehabilitation up to the standard, the scores of the Shoulder Pain and Disability Index (SPADI), Chronic Disease Self-Efficacy Scale (CDSES) and Quality of Life Instrument for Patients with Pacemaker (QLIPP) were compared.Results:The rate of observation group's post-operative rehabilitation up to the standard was 93.33% (42/45), which was higher than that of the control group 77.78% (35/45). The difference was statistically significant ( χ2 =4.41, P<0.05). The pain index of the observation group was (20.27 ± 4.13), (5.25 ± 2.64)points at 1 and 2 weeks after operation, which was significantly lower than (27.06 ± 5.30), (9.35 ± 4.22) points of the control group ( t=6.78, 5.53, both P<0.05). The dysfunction index of the observation group was (15.06 ± 5.96), (7.21 ± 3.68) points, which was significantly lower than (17.75 ± 6.04), (9.03 ± 4.06) points of the control group ( t=2.13, 2.23, both P<0.05). After 2 weeks of operation, the total score of CDSES in the observation group was (4.73 ± 1.68) points, which was higher than (3.67 ± 1.49) points in the control group, and the difference was statistically significant ( t=3.17, P<0.05). The total score of QLIPP in the observation group was (92.78 ± 6.26), (124.40 ± 4.91) points at 2 weeks and 1 month after operation, which was significantly higher than (83.50 ± 7.91), (112.42 ± 5.04) points in the control group ( t=6.17, 9.51, both P<0.05). Conclusions:The application of nursing care based on self-efficacy theory in the patients of early functional exercise of the affected limb after permanent pacemaker implantation can improve rehabilitation compliance, self-efficacy of patients, the function of the affected shoulder joint and the patient′s quality of life.

Advances in applications of molecular dynamics simulation techniques to the research of self-assembled nano-drug delivery systems / 药学学报

Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.