Spatial distribution, influencing factors and innovative development countermeasures of farmer cooperatives in Hunan Province, China.

China's rural reform is reliant on farmers' cooperatives as a key organization vehicle. It plays an important role in promoting rural revitalization. Such as, realizing the organic connection between small farmers and agricultural modernization. This study used the nearest neighbor index and kernel density estimation to analyze the spatial distribution and structural characteristics of farmer cooperatives in Hunan Province. It revealed the spatial differentiation law of cooperatives. Also using geographical detectors to figure out the main factors that affect the spatial distribution. The results show that: ① Hunan Farmers Cooperatives show significant spatial agglomeration. The overall spatial distribution shows the spatial characteristics of "one core, one circle, and multiple points". And the spatial distribution pattern of "large agglomeration, finger-shaped radiation distribution". Among them, the distribution of provincial demonstration cooperatives is relatively balanced. ② Cooperatives in six types of industries, such as planting, forestry, and feeding, showed agglomeration distribution. Different industrial cooperatives spread out in different ways, such as in an anti-"L" shape, a dual-core shape, or a one-center area. ③ The 24 influence factors selected from the five dimensions of the natural environment, social economic basis, production basis, output capacity, and facility basis have high, general, and weak influence on cooperatives' spatial distribution. The development and distribution of cooperatives mainly depend on resource endowment, social and economic development level, and market dependence. The spatial distribution heterogeneity of different professional cooperatives is mainly affected by slope, per capita disposable income of rural residents, road density, and other factors. ④ The progression of farmer cooperatives in Hunan Province should prioritize high-quality development, emphasizing the need for innovative approaches and transformative strategies within rural industrial organizations. It is imperative to optimize the spatial distribution of cooperatives, strategically contributing to the establishment of a novel framework for modern agricultural development in Hunan Province. Additionally, there is a critical emphasis on spearheading collaborative initiatives among cooperatives of varied industrial types, aimed at fostering the integrated development of rural primary, secondary, and tertiary industries.

Prognostic Nutritional Index Enhances the Discriminatory Ability of Procalcitonin for Predicting Pediatric Sepsis.

Objective. Improving diagnostic ability of pediatric sepsis is of great significance for reducing the mortality of sepsis. This study explored the discriminatory capacity of nutritional index (PNI) in pediatric sepsis. Methods. We retrospectively enrolled 134 children with suspected sepsis and collected their clinical and laboratory data. Receiver operating characteristic curves (ROC), decision curve analysis (DCA) and net reclassification improvement (NRI) were performed to compare the predictive significance of the PNI, procalcitonin (PCT) and their combination. Results. Among 134 patients, 65 children were diagnosed with sepsis and 69 children with non-sepsis. PCT and PNI were independently associated with pediatric sepsis. PCT was superior to PNI to predict pediatric sepsis. The model based on PCT + PNI improved the predictive capacity than them alone, as demonstrated by ROC, DCA and NRI, respectively. Conclusion. PNI was independently associated with pediatric sepsis, and addition of PNI could improve the capacity of PCT to predict pediatric sepsis.

Progress on CRISPR/Cas9 system in the genetic improvement of livestock and poultry.

CRISPR/Cas9 gene editing technology, as a highly efficient genome editing method, has been extensively employed in the realm of animal husbandry for genetic improvement. With its remarkable efficiency and precision, this technology has revolutionized the field of animal husbandry. Currently, CRISPR/Cas9-based gene knockout, gene knock-in and gene modification techniques are widely employed to achieve precise enhancements in crucial production traits of livestock and poultry species. In this review, we summarize the operational principle and development history of CRISPR/Cas9 technology. Additionally, we highlight the research advancements utilizing this technology in muscle growth and development, fiber growth, milk quality composition, disease resistance breeding, and animal welfare within the livestock and poultry sectors. Our aim is to provide a more comprehensive understanding of the application of CRISPR/Cas9 technology in gene editing for livestock and poultry.

Artificial LiF-Rich Interface Enabled by In situ Electrochemical Fluorination for Stable Lithium-Metal Batteries.

Lithium (Li)-metal batteries are promising next-generation energy storage systems. One drawback of uncontrollable electrolyte degradation is the ability to form a fragile and nonuniform solid electrolyte interface (SEI). In this study, we propose the use of a fluorinated carbon nanotube (CNT) macrofilm (CMF) on Li metal as a hybrid anode, which can regulate the redox state at the anode/electrolyte interface. Due to the favorable reaction energy between the plated Li and fluorinated CNTs, the metal can be fluorinated directly to a LiF-rich SEI during the charging process, leading to a high Young's modulus (~2.0 GPa) and fast ionic transfer (~2.59×10-7  S cm-1 ). The obtained SEI can guide the homogeneous plating/stripping of Li during electrochemical processes while suppressing dendrite growth. In particular, the hybrid of endowed full cells with substantially enhanced cyclability allows for high capacity retention (~99.3 %) and remarkable rate capacity. This work can extend fluorination technology into a platform to control artificial SEI formation in Li-metal batteries, increasing the stability and long-term performance of the resulting material.

Experimental Study on the Diffusion Law of Coal-Based Solid Waste Slurry with Grouting Filling in the Gangue Voids of the Caving Zone.

Due to the concealment of the caving zone, it is difficult to detect and grasp the diffusion law of the slurry in the voids of the gangue pile. On the preparation of reasonable grouting filling materials, a large-scale three-dimensional gangue grouting filling test system has been established to detect the slurry pressure and resistivity inside the gangue pile and analyze the flow pattern of the slurry in the voids of the gangue pile. The research results show that the slump and bleeding rate of the filling slurry are significantly reduced with the increase of the fly ash content. The optimal ratio of fly ash, coal gangue, and gasification slag is 7:2:1, with a mass fraction of 72%. In the process of grouting, the internal pressure of the gangue pile can be divided into the initial stable stage, the step growth stage, and the pressure stability stage, and the change curve of the pressure sensor at the lower level is similar. The resistance value of the original broken gangue in the experiment is approximately 1600 Ω. Grouting filling forms a slurry-rock mixture, and its resistance continuously decreases with the stable injection of the slurry (minimum value 150 Ω). It is determined that the slurry near the grouting hole mainly diffuses longitudinally with a good void filling effect. The void channels of slurry diffusion are randomly distributed and have different shapes, which hinder slurry flow and diffusion. Slurry particles accumulate and settle at local small voids. Meanwhile, the surface of the gangue blocks is dry, and the slurry absorbs part of the water during diffusion, resulting in the increase of the slurry concentration and the weakening of the lateral diffusion ability. Secondary or multiple grouting can effectively fill the void of the broken gangue and further improve the filling effect.

Treatment of Bone and Joint Diseases with Gancao Fuzitang： A Review / 中国实验方剂学杂志

Gancao Fuzitang originates from the Treatise on Febrile Diseases and Miscellaneous Diseases （《伤寒杂病论》） and is mainly used to treat pain in the bones and joints and symptoms such as no flexion or extension. It has the effect of tonifying the spleen and kidney and removing dampness and turbidity， so it is widely used in the clinical treatment of various bone and joint diseases. This article reviewed the clinical research and mechanism of Gancao Fuzitang in the treatment of bone and joint diseases. The research has found that this prescription has good efficacy in treating bone and joint diseases such as rheumatoid arthritis， rheumatoid arthritis， ankylosing spondylitis， gout， and intervertebral disc herniation. Its mechanism of action may be related to regulating the level of inflammatory factors， antioxidation， and the protein expression of inflammatory and apoptotic cell-related pathways， improving bone and joint diseases， and alleviating related symptoms. This study can provide a reference for further deepening the research on the prevention and treatment of bone and joint diseases with Gancao Fuzitang.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine（Part 5）： Retrieval and Synthesis of Key Information on Rational Drug Use / 中医杂志

Recommendations for Chinese patent medicine （CPM） based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study， we discussed in detail of the key information on the rational use of CPM in five aspects， which are dosage， drug discontinuation， drug-drug and drug-food interactions， safety and economy. Following the process of multi-source search， synthesis and prioritization， it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions， policy documents， literature， and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally， methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.

Methodology for the Development of Clinical Practice Guideline for Chinese Patent Medicine（Part 1）： Development Status and Characteristics / 中医杂志

The irrational use of Chinese patent medicines （CPM） is becoming more and more prominent， which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines， and promote its development， this paper introduced the concept of CPM guidelines， summarized the characteristics of the two development modes， namely “taking CPM as the key” and “taking disease/syndrome as the key”， and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems， three suggestions have been put forward to optimize the quality of CPM guidelines， which were clarifying the target users and scope of CPM guidelines， establishing an open and transparent mechanism of the personnel involvement and process steps， and formulating implementable and operable recommendations for the use of CPM.

Evaluation of asymptomatic ocular surface disorders in hospitalized patients with primary pterygium before surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

Interpretation of the Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine：weighting of evaluation indicators / 中国药房

OBJECTIVE To provide a detailed report and interpretation of the method and results for determining the weights of the technical indicators from the “multi-dimensional and multi-criteria comprehensive evaluation index system （first edition）” stated in Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine. METHODS Normalization calculations were performed on the comprehensive weight values calculated by the analytic hierarchy process and expert weighting method to obtain the objective weights of the indicators. RESULTS The weight results of the six primary dimensions in the current comprehensive evaluation indicator system of Chinese patent medicine showed effectiveness dimension＞ safety dimension＞standard dimension＞application dimension＞scientific dimension＞economic dimension， with weight values of 0.281 0， 0.268 5， 0.195 8， 0.107 3， 0.096 1 and 0.051 3 respectively， consistent with the results of most researches currently. CONCLUSIONS The process of weight determination in this indicator system is scientifically reasonable， with clear methods and clear interpretations， and is worthy of further optimization and widespread application.

Sishenwan Combined with Tongxie Yaofang Treats Ulcerative Colitis with Spleen-kidney Yang Deficiency and Liver Depression / 中国实验方剂学杂志

ObjectiveTo induce the rat model of ulcerative colitis （UC） with spleen-kidney Yang deficiency and liver depression， and explore the efficacy and mechanism of Sishenwan combined with Tongxie Yaofang （SSW&TXYF） based on the therapeutic principles of tonifying spleen， soothing liver， warming kidney， and astringing intestine. MethodSixty male SD rats were randomized into normal， model， mesalazine， and high-， medium-， and low-dose SSW&TXYF groups. The rats in other groups except the normal group were administrated with Sennae Folium decoction and hydrocortisone and received tail clamping for 14 days. On day 14， rats received enema with TNBS-ethanol solution to induce UC. The rats were administrated with corresponding drugs from day 15 of modeling， and the body weight and mental state were observed and recorded. The sucrose preference test was performed from day 25. On day 28， the rectal temperature was measured， and the rats were administrated with 3% D-xylose solution at a dose of 10 mL·kg-1 by gavage. Blood was sampled 1 h later， from which the serum was collected for measurement of the D-xylose content. The serum， hippocampus， and colorectum samples of rats were collected on day 29. The levels of gastrin （GAS）， adrenocorticotropic hormone （ACTH）， corticosterone （CORT）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， interleukin （IL）-4， tumor necrosis factor （TNF）-α， and interferon （IFN）-γ in the serum and 5-hydroxytryptamine （5-HT） in the hippocampus were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the colonic lesions. The mRNA and protein levels of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， and c-Jun N-terminal kinase （JNK） in the colon tissue were determined by Real-time PCR and Western blot， respectively. ResultCompared with the normal group， the model group showed decreased body weight， anal temperature， and D-xylose content in the serum and increased GAS content （P<0.01）. The modeling led to cAMP/cGMP unbalance and decreased the ACTH and CORT content in the serum （P<0.01）， the preference for sucrose water， and the 5-HT content in the hippocampus （P<0.01）. Moreover， it shortened the colorectal length and caused massive infiltration of inflammatory cells and severe structural damage in the colon tissue. High， medium， and low doses of SSW&TXYF improved above indicators （P<0.05， P<0.01）， reduced inflammatory infiltration， and repaired the pathological damage of the tissue. Compared with the normal group， the model group showed lowered IL-4 level （P<0.01） and elevated TNF-α and IFN-γ levels （P<0.05， P<0.01） in the serum， as well as up-regulated expression of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. Compared with the model group， SSW&TXYF elevated the IL-4 level （P<0.01）， lowered the TNF-α and IFN-γ levels （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. ConclusionA rat model of UC with spleen-kidney Yang deficiency and liver depression was successfully established. SSW&TXYF can significantly mitigate this syndrome by reducing the inflammatory response in the colon and inhibiting the MAPK pathway.

Regulatory mechanisms of the cAMP-responsive element binding protein 3 (CREB3) family in cancers.

The CREB3 family of proteins, encompassing CREB3 and its four homologs (CREB3L1, CREB3L2, CREB3L3, and CREB3L4), exerts pivotal control over cellular protein metabolism in response to unfolded protein reactions. Under conditions of endoplasmic reticulum stress, activation of the CREB3 family occurs through regulated intramembrane proteolysis within the endoplasmic reticulum membrane. Perturbations in the function and expression of the CREB3 family have been closely associated with the development of diverse diseases, with a particular emphasis on cancer. Recent investigations have shed light on the indispensable role played by CREB3 family members in modulating the onset and progression of various human cancers. This comprehensive review endeavors to provide an in-depth examination of the involvement of CREB3 family members in distinct human cancer types, accentuating their significance in the pathogenesis of cancer and the manifestation of malignant phenotypes.

Evaluation of Fourier transform infrared (FTIR) spectroscopy with multivariate analysis as a novel diagnostic tool for lymph node metastasis in gastric cancer.

Fourier transform infrared (FTIR) spectroscopy is a vibration spectroscopy that uses infrared radiation to vibrate to absorb the molecular bonds in its absorbed sample. The main purpose of this study was to evaluate FTIR spectroscopy as a novel diagnostic tool for lymph node metastasis (LNM) of gastric cancer. We collected 160 fresh non-metastatic and metastatic lymph nodes (80 each) from 60 patients with gastric cancer for spectral analysis. FTIR spectra of lymph node (LN) samples were obtained in the wavenumber range of 4000 cm-1 to 900 cm-1. We calculated the changes in the ratio of spectral intensity (/ I1460). Principal component analysis (PCA) and Fisher's discriminant analysis (FDA) were used to distinguish malignant from normal LN. Four significant bands at 1080 cm-1, 1640 cm-1, 1740 cm-1 and 3260 cm-1 separated metastatic and non-metastatic LN spectra into two distinct groups by PCA.T-tests showed that, along with the relative intensity ratios (I1080/I1460, I1640/I1460, I3260/I1460, I1740/I1460), these band ratios were also able to differentiate between malignant and benign LN spectra. Six parameters (P1080 cm-1, P1300 cm-1, I1080/I1460, I1640/I1460, I3260/I1460, I1740/I1460) were selected as independent factors to set up discriminant functions. The sensitivity of FTIR spectroscopy in diagnosing LNM was 95 % by discriminant analysis. Our study suggested that FTIR spectroscopy can be a useful tool to examine LNM with high sensitivity and specificity for LNM diagnosis. Therefore it can be used in clinical practice as a non-invasive method.

Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.@*METHODS@#Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.@*RESULTS@#Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01).@*CONCLUSION@#EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Concerns of Technical Evaluation on Registration of All-inside Meniscus Suture System / 中国医疗器械杂志

OBJECTIVE@#To summarize the product registration declaration ideas and registration technical review of the all-inside meniscal suture system, and to systematically think about of the technical review concerns of the all-inside meniscal suture system products to provide technical guidance for improving the quality of registration and application and regulatory efficiency.@*METHODS@#Consult the public information of such products at home and abroad, and summarize the experience of registration review of such products.@*RESULTS@#The technical review of the all-inside meniscus suture system registration mainly focuses on product basic information, pre-clinical research, clinical evaluation and product technical requirements.@*CONCLUSIONS@#The difficulty of product registration and declaration of the all-inside meniscus suture system lies in the provision of pre-clinical research data of the product, and the applicant needs to strengthen the basic research ability, formulate scientific technical indicators and test methods to ensure the safety and effectiveness of the product, and also provide sufficient supporting data for the registration declaration.

Research on Life Cycle Management of Medical Consumables Based on Hospital Resource Planning System / 中国医疗器械杂志

OBJECTIVE@#In order to improve the compatibility of the hospital resource planning (HRP) system for the whole life cycle of medical consumables, and to improve the management and control capabilities of hospital institutions on medical consumables.@*METHODS@#Based on the traditional HRP system, a secondary development and design of a medical consumables whole life-cycle artificial intelligence module was conducted, and a neural network machine learning algorithm module was introduced to enhance its big data integration and analysis capabilities.@*RESULTS@#The simulation analysis found that after adding this module, the proportion of minimum inventory, the proportion of procurement cost difference and the expiration rate of consumables all decreased significantly, and the differences were statistically significant (P<0.05).@*CONCLUSIONS@#The whole life cycle module of medical consumables based on HRP system can effectively improve the management efficiency of hospital medical consumables, adjust the warehouse inventory management ability, and improve the overall management level of medical consumables.

Study of Typical Functional Failure and Mechanical Properties of Non-absorbable Suture Anchor / 中国医疗器械杂志

OBJECTIVE@#To study the mechanical properties related to the typical functional failure modes of non-absorbable suture anchor in clinical use, and to support product design, development and verification.@*METHODS@#By retrieving the database of relevant adverse events, the typical functional failure modes of non-absorbable suture anchor were summarized, and the influencing factors of functional failure were further analyzed by studying the mechanical properties related to functional failure. The publicly available test data was retrieved for verification and provided reference for the researchers.@*RESULTS@#The typical functional failure modes of non-absorbable suture anchor include anchor failure, suture failure, fix loosening, inserter failure, which are related to the mechanical properties of products, such as screw-in torque and break torque of screw-in anchors, insertion force of knock-in anchors, suture strength, pull-out force before and after system fatigue test and elongation of sutures after fatigue test.@*CONCLUSIONS@#Enterprises should pay attention to improving the mechanical performance level of products through material, structural design and the suture weaving process to ensure the safety and effectiveness of products.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease / 老年心脏病学杂志（英文版）

BACKGROUND@#Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers.@*METHODS@#A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death.@*RESULTS@#Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years.@*CONCLUSIONS@#Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Mining Novel Anti-Nocardia Drug Targets Based on Pan-genomics and Subtractive Proteomics / 中山大学学报(医学科学版)

ObjectiveNocardia is an apathogen that causes opportunistic infections in humans and has a global distribution. In recent years， resistance of Nocardia to commonly used drugs have been observed， highlighting the urgent need for the identification of new drug targets and the development of novel antimicrobial agents against Nocardia. MethodsThirty-one complete genome sequences of Nocardia strains were retrieved from the GenBank database. Pan-genomic analysis was performed using BPGA， and drug target candidates were screened using subtractive proteomics. Homology modeling was employed to predict the 3D structures of target proteins， and potential drugs targeting these proteins were predicted using DrugBank. Molecular docking techniques were utilized to validate the binding activity between the drugs and target proteins. ResultsThe pan-genomic analysis of the 31 Nocardia strains revealed 1 421 core proteins. Fifteen candidate drug target proteins were identified through subtractive proteomics analysis. Among them， the physicochemical properties of the OG1493 protein （such as amino acid count， molecular weight， isoelectric point， grand average of hydropathicity， fat index，and instability index Ⅱ） were found to be most suitable for a drug target protein. Using the DrugBank database， seven compounds， namely Adenosine-5'-Rp-Alpha-Thio-Triphosphate， alpha，beta-Methyleneadenosine 5'-triphosphate， Phosphoaminophosphonic Acid-Adenylate Ester ，Radicicol，2-Hydroxyestradiol， p-Coumaric acid， and Ethylmercurithiosalicylic acid were identified as potential compounds capable of exerting anti-Nocardia effects by targeting this protein. Molecular docking results indicated a strong binding affinity between the target protein and these compounds. The experimental result showed that that Radicicol could be a potential antibacterial drug targeting this particular protein. ConclusionPan-genomic analysis and subtractive proteomics are valuable approaches for mining novel anti-Nocardia drug targets.

Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.@*METHODS@#The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.@*RESULTS@#There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.@*CONCLUSION@#The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.