ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

The molecularly imprinted polymers membranes(MIPMs)were prepared for selective adsorption of lamotrigine(LTG)in plasma by surface molecular imprinting technology with polyvinylidenefluoride(PVDF)membranes as supporter,lamotrigine as template molecule,methyl methacrylate as functional monomer,ethylene glycol dimethacrylate as cross-linking agent,azodiisobutyronitrile as initiator and acetonitrile-dimethylformamide(1∶1.5,V/V)as pore-forming agent.The prepared MIPMs were characterized by scanning electron microscope,Fourier transform infrared spectroscopy,Brunaner-emmet-teller measurements,X-ray photoelectron spectroscopy,and thermogravimetric analysis.The adsorption properties of the materials were investigated by kinetic adsorption,isothermal adsorption,selective adsorption,adsorption-desorption and reusability experiments.The results showed that the imprinted layer of LTG was successfully coated on the surface of PVDF,and the materials had uniform particle size.The adsorption capacity and imprinting factor of the MIPMs towards LTG were 3.77 mg/g and 8.97,respectively.The nanomaterials showed fast mass transfer rate(30 min)and good reusability(the adsorption efficiency was 86.66%after 6 cycles),and could be used for the adsorption of LTG in plasma with low matrix interference,recoveries of 86.54%-90.48%and RSD of 1.51%-3.15%(n=5).The proposed LTG MIPMs were demonstrated to be simple and environment friendly,and had high selectivity in rapid separation and extraction of LTG in plasma.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To study the mechanism of polyene phosphatidylcholine in improving metabolic disorders and fatty liver induced by high fat diet.Methods Thirty-two C57BL/6 mice were randomly divided into blank group,control group,model group and experimental group.The blank group was fed with low-fat diet and intraperitoneal injection of 10％glucose 200 μL twice a week.Control group was fed with low-fat diet twice a week and intraperitoneally injected 10％glucose solution 200 μL containing polyene phosphatidylcholine(PPC)20 μg.Model group was fed with high-fat diet and intraperitoneal injection of 10％glucose 200 μL twice a week.Experimental group was fed with high-fat diet twice a week and intraperitoneally injected 10％glucose solution 200 μL containing PPC 20 μg.The body weight of the mice was measured,blood glucose test strips and insulin resistance was analyzed.The levels of triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),glutamic oxalic aminotransferase(GOT)and glutamic pyruvic aminotransferase(GPT)in serum and liver were analyzed by biochemical method.The levels of tumor necrosis factor-α(TNF-α),interleukin-6 and IL-8 were detected by enzyme-linked immunosorbent assay(ELISA).Results The serum TG levels of blank group,control group,model group and experimental group were(0.15±0.01),(0.11±0.01),(0.21±0.01)and(0.12±0.01)mmol·L-1;LDL levels were(0.41±0.01),(0.25±0.01),(0.71±0.02)and(0.49±0.01)mmol·L-1;GOT levels were(30.30±0.89),(31.39±1.18),(43.04±2.82)and(25.64±0.72)mmol·L-1;GPT levels were(9.15±0.45),(7.39±1.88),(12.87±1.81)and(7.96±1.64)mmol·L-1;fasting blood glucose levels were(4.97±0.08),(6.08±0.18),(8.12±0.20)and(7.29±0.02)mmol·L-1;fasting insulin levels were(6.52±1.11),(5.45±0.28),(54.83±4.32)and(30.55±2.73)mU·L-1;the levels of TNF-α in liver tissues were(3.98±0.63),(3.95±0.98),(20.55±4.71)and(15.28±1.73)pg·g-1;IL-6 levels were(18.93±8.56),(17.64±3.29),(59.40±4.63)and(37.54±7.33)pg·g-1;IL-8 levels were(67.16±12.37),(59.44±3.58),(198.40±9.27)and(132.10±7.04)pg·g-1.The difference of above indicatory between experimental group and model group was statistically significant(all P＜0.05).Conclusion Polyene phosphatidylcholine may inhibit the expression of TNF-α,IL-6 and IL-8 inflammatory factors by mediating the inhibition of inflammation on liver tissue and then improve metabolic disorders.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

Objective: To investigate the comorbidity of myopia and scoliosis among primary and secondary school students in Tianjin, and to analyze the school environment risk factors contributing to these health issues, so as to provide a scientific basis for development effective prevention measures. Methods: A total of 41 654 primary and secondary school students from 16 districts of Tianjin were selected by stratified random cluster sampling from September to October 2023 to screen for myopia and scoliosis. Univariate analysis was performed to examine the data, followed by a bivariate multivariate Logistic regression model and cumulative effect analysis to explore the influencing factors of their comorbidity. Results: In 2023, the prevalence of comorbidity of screening positive myopia and scoliosis among primary and secondary school students in Tianjin was 2.65%. The prevalence was higher in suburban areas (3.26%) compared to urban areas (2.02%), higher among females (3.81%) compared to males (1.59%), and highest in high school students (6.17%) compared to middle school (4.19%) and primary school students (0.44%) (χ2=62.23, 198.69, 953.19, P<0.01). Logistic regression analysis showed that the number of physical education classes ≥3 per week, the number of eye health exercises at school ≥2 per day, outdoor activities between classes, teachers reminding to pay attention to reading and writing posture and strict eye standing posture were negatively correlated with the comorbidity of screening positive myopia and scoliosis (OR=0.66, 0.77, 0.71, 0.78, 0.74, P<0.05). Reading or electronic screen while lying or lying on the stomach was positively associated with the comorbidity of screening positive myopia and scoliosis (OR=1.77, P<0.05). Cumulative effect analysis showed that the cumulative score (4-7, 7-9, ≥10) was negatively correlated with the comorbidity of screening positive of myopia and scoliosis (OR=0.65, 0.55, 0.52, P<0.05). Conclusions The school environment support and students personal behavior habits in school are related to the comorbidity of comorbidity of screening positive myopia and scoliosis. Prevention and control of myopia and scoliosis should improve the environmental factors related to students health in school.

Objective To investigate the association of sleep disorders with the development and progression of nonalcoholic fatty liver disease(NAFLD).Methods A total of 1 868 participants from the health examination cohort and fatty liver cohort of Beijing Friendship Hospital from June 2022 to June 2023 were enrolled as subjects.Related data were collected from all subjects,including age,sex,education level,chronic medical history,and biochemical parameters,and all subjects completed Pittsburgh Sleep Quality Index(PSQI)scale independently.According to the diagnostic criteria,the subjects were divided into non-NAFLD group with 1 122 subjects and NAFLD group with 746 subjects,and according to the stage of progression,the patients in the NAFLD group were further divided into simple fatty liver group(SFL group with 624 subjects)and nonalcoholic steatohepatitis(NASH)group with 122 subjects.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between three groups.The chi-square test was used for comparison of categorical data between the three groups.The binary Logistic regression analysis was used to investigate the association between sleep factors and NAFLD,and the multinomial Logistic regression analysis was used to investigate the association between sleep factors and the different stages of NAFLD;two multivariate models were constructed for adjustment of potential confounding factors,i.e.,an age-sex adjustment model and a multivariate adjustment model,and the multivariate adjustment model adjusted the factors of age,sex,education level,smoking,diabetes,hypertension,body mass index(BMI),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C).Results There were significant differences in age,sex,BMI,education level,smoking,diabetes,hypertension,alanine aminotransferase,TG,and HDL-C between the non-NAFLD,SFL,and NASH groups(all P<0.05).There were also significant differences between the three groups in the total score of PSQI scale and the proportion of subjects with a score of 0—3 points for the 7 sleep components(all P<0.05).The multivariate adjustment model showed no significant association between sleep disorders and SFL,while long sleep latency(odds ratio[OR]=4.04,95%confidence interval[CI]:2.33—7.03,P<0.001),short sleep duration(OR=3.53,95%CI:1.83—6.82,P<0.001),and severe sleep disorders(OR=2.96,95%CI:1.48—5.93,P=0.002)were closely associated with the risk of NASH.Conclusion Overall sleep condition and its components of sleep disorders are not significantly associated with the simple fatty liver;however,long sleep latency,short sleep duration,and severe sleep disorders can increase the risk of NASH,which should be taken seriously in clinical practice.