Drug-free targeted thrombolytic strategy based on gold nanoparticles-loaded human serum albumin fusion protein delivery system / 药学学报

Thrombus is a major factor leading to cardiovascular diseases such as myocardial infarction and stroke. Although fibrinolytic anti-thrombotic drugs have been widely used in clinical practice, they are still limited by narrow therapeutic windows, short half-lives, susceptibility to inactivation, and abnormal bleeding caused by non-targeting. Therefore, it is crucial to effectively deliver thrombolytic agents to the site of thrombus with minimal adverse effects. Based on the long blood circulation and excellent drug-loading properties of human serum albumin (HSA), we employed genetic engineering techniques to insert a functional peptide (P-selectin binding peptide, PBP) which can target the thrombus site to the N-terminus of HSA. The fusion protein was expressed using Pichia pastoris and purified by Ni-chelating affinity chromatography. After being loaded with gold nanoparticles (Au NPs), the fusion protein formed homogeneous and stable nanoparticles (named as PBP-HSA@Au) with a diameter of 17.7 ± 1.0 nm and a zeta potential of -11.3 ± 0.2 mV. Cytotoxicity and hemolysis tests demonstrated the superb biocompatibility of PBP-HSA@Au. Platelet-targeting experiments confirmed the thrombus-targeting ability conferred by the introduction of PBP into PBP-HSA@Au. Upon near-infrared ray (NIR) irradiation, PBP-HSA@Au rapidly converted light energy into heat, thereby disrupting fibrinogen and exhibiting outstanding thrombolytic efficacy. The designed HSA fusion protein delivery system provides a precise, rapid, and drug-free treatment strategy for thrombus therapy. This system is characterized by its simple design, high biocompatibility, and strong clinical applicability. All animal experiments involved in this study were carried out under the protocols approved by the Animal Experiment Ethics Committee of Jiangnan University [JN. No20230915S0301015(423)].

Mechanism and treatment of mucous hypersecretion in chronic obstructive pulmonary disease / 中国临床药理学与治疗学

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchos-copy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.

Simultaneous detection of 7 important Rickettsiales pathogens by TaqMan-probe quantitative real-time PCR / 中华流行病学杂志

Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R2 >0.990 0), the minimum detection limit was 10 copies/μl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.

Relationship between Dining Place, Iodine Source, and Iodine Nutrition in School-Age Children: A Cross-Sectional Study in China / 生物医学与环境科学（英文）

OBJECTIVE@#This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children.@*METHODS@#School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables.@*RESULTS@#Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status.@*CONCLUSION@#Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.

Association of serum complement C3, C4 with renal pathological lesion degree in IgA nephropathy patients / 中华肾脏病杂志

Objective:To explore the relationship between the levels of serum complement C3 and C4 and the degree of renal pathological injury in patients with IgA nephropathy (IgAN).Methods:It was a retrospective study. The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the Department of Nephrology of the Second People's Hospital of Qujing City, Yunnan Province from December 1, 2019 to December 31, 2022 were collected. According to the IgAN Oxford classification criteria, the patients were divided into mild renal pathological injury group (mild group, <3 pathologic types) and severe renal pathological injury group (severe group, ≥3 pathological types). The levels of serum C3 and C4 and other clinical data were compared between the two groups. Spearman correlation method was used to analyze the correlation between serum C3, C4 levels and estimated glomerular filtration rate (eGFR) during renal biopsy.Multivariate logistic regression model was used to analyze the influencing factors of the pathological injury degree in IgAN patients and the forest map depicted the effect of risk factors.Results:A total of 164 IgAN patients were included in the study, including 77 males (47.0%), aged (35.5±12.9) years old. There were 60 patients in the mild group and 104 patients in the severe group. Compared with the mild group, the patients in the severe group were older, had higher levels of serum C4, serum uric acid, low density lipoprotein cholesterol and 24 h urinary protein, higher proportions of hypertension, glucocorticoids/immunosuppressant therapy, C3 deposition in renal tissues and microscopic hematuria, and had lower hemoglobin and serum C3 level (all P<0.05). The results of Spearman correlation analysis showed that the level of serum C3 was positively correlated with eGFR ( r=0.303, P<0.001), and the level of serum C4 was negatively correlated with eGFR ( r=-0.238, P=0.002). Multivariate logistic regression analysis results showed that serum C3 (every 0.01 g/L increase, OR=0.976, 95% CI 0.957-0.996, P=0.018), serum C4 (every 0.01 g/L increase, OR=1.091, 95% CI 1.020-1.166, P=0.011), hemoglobin ( OR=0.969, 95% CI 0.950-0.988, P=0.002), and serum uric acid ( OR=1.005, 95% CI 1.001-1.009, P=0.012) were independent related factors of renal pathological damage (severe injury /mild injury) in IgAN patients. Conclusions:Serum C3 and C4 are independent related factors of the severity of renal pathological injury in IgAN patients.

Brain removal through a posterior incision on the scalp of both ears / 解剖学报

Objective The traditional round incision or cross incision brain harvesting method can not meet the requirements of protecting the donor's remains. In this study, the method of brain removal through a posterior incision on the scalp of both ears was proposed, which effectively protected the donor's remains. Methods Adopting the incision 2. 0 cm above the external occipital protuberance to the most front edge of the auricle to obtain a complete brain. Results The incision did not involve the head and face skin, which was small and conducive to suture repair and reduce exudation. Conclusion The incision effectively protects the donor' s remains, and it will be conducive to the establishment and development of the brain bank.

Changes of Nogo-A expression in hippocampus and striatum of rats under low estrogen condition / 解剖学报

[Abstract] Objective To elucidate the important role of Nogo-A in climacteric neurodegeneration such as memory impairment by observing memory function and the expression of Nogo-A in hippocampus and striatum of rats under low estrogen condition. Methods Fouthy-five female SD rats were divided into sham operation group, ovariectomized group and ovariectomized estrogen treatment group with 15 rats in each group. Medication was given 2 weeks after ovariectomized. Estrogen treatment group was subcutaneously injected in groin with estrogen [25 μg/ (kg.d)] dissolved in sterile sesame oil. The sham operation group and the ovariectomized group were given the same amount of aseptic sesame oil. Samples were collected after 6 weeks of drug treatment. The difference of memory function of rats in three groups was observed by conditioned fear training experiment, and the expression of Nogo-A in hippocampus and striatum was observed by immunohistochemistry and Western blotting. Results Compared with the sham and estrogen treatment group, memory function in ovariectomized group decreased significantly and the number of Nogo-A positive neurons in hippocampus and striatum of ovariectomized rats was significantly higher than that of sham operation group (P 0. 05). The result of immunoblotting was consistent with the above-mentioned immunohistochemical result. Conclusion The increased expression of Nogo-A in hippocampus and striatum under low estrogen condition may be one of the key reasons for memory impairment in climacteric women.

Discussion on the establishment of health management as Master degree awarding program under first-level discipline of clinical medicine / 中华医学教育探索杂志

Based on the status and development of the majors and degrees at home and abroad, the relationship between health management sciences and their close secondary disciplines, course setting, and the demand for health management talents in society, this study elaborates the foundations of setting health management disciplines and the prospects of the discipline, and demonstrates the importance of the discipline construction of health management.

Exploration of human resource allocation management of multi-campus public hospitals / 中华医院管理杂志

The multi-campus hospital mode plays an important role in fully leveraging the advantages of public hospitals, and promoting both the expansion of high-quality medical resources and the balanced regional layout. The authors analyzed the current situation and existing problems of human resource allocation of the multi-campus mode of a provincial tertiary hospital, and summarized its practice of optimizing such allocation by improving the top-level organizational framework design, coordinating the construction of talent echelons, and effectively allocating human resources. These experiences can provide references for human resources management in such a mode.

Corrigendum to “Discovery and identification of quality markers of Sparganii Rhizoma based on zebrafish thrombosis model” Chin. Herb. Med. 13 (2021) 389–395 (Chinese Herbal Medicines (2021) 13(3) (389–395), (S1674638421000654), (10.1016/j.chmed.2021.04.015)) / 中草药·英文版

When this paper was first published, the authors’ affiliation

Imiquimod inhibiting the proliferation of gliocytoma U87 cells by down-regulating STAT3/nuclear factor-KB signal pathway / 解剖学报

Objective To explore the effect of imiquimod (IMQ) on the proliferation of glioma U87 cell line U87. Methods U87 cells were divided into control group, 1 mmol/L I mmol/L MQ group, 5 mmol/L IMQ group, 1 mmol/L IMQ+ STAT3 inhibitor(STAT3-IN) group and 5 mmol/L IMQ + STAT3-IN group. To detect the number of 5-ethynyl-2 ' - deoxyuridine(EdU) -labeled cells or proliferation absorbance(A) values in each group by EdU and MTT assays. Interleukin (I L) - 6 mRNA, tumor necrosis factor (TNF) -a mRNA and protein content in U87 cells of each group were detected by Real-time PCR or ELISA. Western blotting was used to detect the protein expression of STAT3, phosphorylated STAT3 (p - S T A T 3), nuclear factor (N F) -KB and phosphorylated NF-KB (p-NF-KB) in U87 cells of each group. Results Compared with the control group, the number of EdU-labeled cells and absorbance values of U87 cells were successively decreased in 1 mmol/L IMQ group and 5 mmol/L IMQ group, showing a dose-dependent manner (P < 0 . 0 1, n— 1 0) . However, the number of EdU-labeled cells and the A values in IMQ + STAT3-IN group and 5 mmol/L IMQ + STAT3-IN group were significantly reduced. Compared with the control group, the protein expression of STAT3, p-STAT3, N F - K B, P ~ N F - K B, IL-6 and TNF-a were continuing low level in U87 cells of 1 mmol/L IMQ group and 5 mmol/L IMQ group (P < 0 . 0 1, * = 1 0) . As well as in 1 mmol/L IMQ + STAT3-INgroup and 5 mmol/L IMQ + STAT3-IN group, the proteins of above were low expressed (P < 0 . 01, n— 10) . Conclusion Imiquimod decreased the contents of IL-6 and TNF-a by down-regulating S T A T 3 / N F - K B pathway, and thus inhibited the proliferation of U87 cells.

Research progress on the relationship between Nogo protein and myocardial fibrosis / 解剖学报

Nogo protein is the fourth member of reticulin famity. Nogo mRNA produced by encoding gene transcription, forms three different RNA transcripts due to different promoter and splicing modes, namely Nogo-A, Nogo-B and Nogo-C protein. Nogo protein was first found in the central nervous system, and then proved to be widely expressed in peripheral tissues such as heart, liver and vascular endothelium. Studies have shown that Nogo protein can participate in the regulation of myocardial fibrosis through RhoA/Rho-associated kinase(ROCK) pathway, endoplasmic reticulum stress, Sce61 a and other signaling pathways. In this paper, the relationship between Nogo-A, Nogo-B, Nogo-C and myocardial fibrosis is briefly introduced.

Establishment of An Animal Model of Acute B Lymphoblastic Leukemia with Minimal Residual Disease / 中国实验血液学杂志

OBJECTIVE@#To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease.@*METHODS@#The transplanted tumor was formed by subcutaneous injection of 2×107 Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis.@*RESULTS@#There were 2×107 Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections.@*CONCLUSION@#The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.

Practice of international talents training project for hospitals / 中华医院管理杂志

Talents constitute key resources for the development of healthcare sector, and studying abroad is an important and effective means for their training. Based on the analysis of the current status of China′s international talents training project of hospitals, this study summarized existing problems in such training. The authors covered such six aspects as lawful standardization of project management methods, selection of trainees by levels and by types, innovation of the process tracking management mechanisms and strengthened full-process assessment, all dimensional institutional support, consolidation of the responsibilities by individual disciplines in talent team building, and measures to cope with the impact of COVID-19. In accordance with the research results, the study analyzed the exploration and practice of the international training project under the " Elite Talents Cultivation Project" of the Affiliated Hospital of Qingdao University, and raised targeted recommendations on attention to the strategic and forward-looking planning, precise setup of training goal categories, classified evaluation of study results, and lawful management among others.

Discovery and identification of quality markers of Sparganii Rhizoma based on zebrafish thrombosis model / 中草药·英文版

Objective: The aim of the present study was to determine the quality marker (Q-Markers) of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect, content determination and spectrum-effect correlation analysis. Methods: Based on the concept of Q-Marker, Sparganii Rhizoma was investigated for the identification of chemical component. The pharmacological effects on arachidonic acid-induced thrombosis in zebrafish were also investigated. The material basis in ethanol extract was determined by HPLC-UV. Furthermore, the potential Q-Markers were analyzed and predicted according to the effect-chemical correlation analysis. Finally, the anti-thrombotic Q-Markers were verified through the anti-thrombotic test of monomer components. Results: The model of thrombosis zebrafish was established with larvae exposed to 100 µmol/L arachidonic acid for 1 h. Nine ingredients in Sparganii Rhizoma were identified as 5-hydroxymethylfurfural, vanillic acid, ferulic acid, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, vanillin, protocatechuic acid, p-coumaric acid and isoferulic acid. According to the determination effect of zebrafish thrombosis model and HPLC content analysis results, all the other contents present positive correlation except 5-hydroxymethylfurfural, and the P values of three representative potential Q-Markers (ferulic acid, protocatechuic acid and p-coumaric acid) were 0.002, 0.001 and 0.026, respectively. Conclusion: Sparganii Rhizoma showed a dose-dependent effect on the recovery of reducing cardiac red blood cell on zebrafish model. Three phenolic acids (ferulic acid, protocatechuic acid and p-coumaric acid) were proved to possess the anti-thrombotic effects which could be regarded as the potential Q-Markers for quality assessment of Sparganii Rhizoma.

Review on the relationship between sphingolipid metabolism and cardiovascular diseases / 解剖学报

As bioactive lipids, sphingolipids participate in the signal transduction of many important physiological processes such as growth and apoptosis. Besides, abnormal levels of sphingolipids were detected in a variety of clinical conditions including hypertension and coronary heart disease, suggesting that sphingolipid metabolism is involved in the occurrence and development of cardiovascular diseases. This paper reviewed the relationship between sphingolipid metabolism with four common cardiovascular diseases, coronary heart disease, hypertension, arrhythmia and heart failure, and the mechanisms involved. What's more, the prospect of sphingolipid pathway as a potential target for the diagnosis and treatment of cardiovascular diseases is put forward.

Distribution of Nogo in the heart and its role in cardiovascular disease / 解剖学报

As a member of the reticulin family, Nogo is mainly involved in processes such as tissue regeneration, apoptosis and tumor growth after tissue injury. Cardiovascular disease is one of the main diseases that threaten human health at present. In recent years, research on Nogo in the cardiovascular system has become increasingly extensive. Changes in the expression of Nogo during myocardial fibrosis, myocardial cell apoptosis and vascular remodeling suggest that it may play a certain role. This article reviews the distribution of Nogo in the heart and its role in cardiovascular disease, in order to reveal its possible role and mechanism in cardiovascular diseases.

Mechanism of KNDy neurons in arcuate nucleus of hypothalamus involved in the occurrence of perimenopausal hot flashes / 解剖学报

Hot flashes are the most common specific symptom of perimenopausal women, which seriously endangers their physical and mental health and quality of life. Because the pathogenesis of hot flashes is not yet clear, and existing estrogen replacement therapy has many limitations and contraindications, it is particularly urgent and important to explore the pathogenesis of hot flashes and find new therapeutic targets. Recent studies suggest that abnormalities of KNDy neurons in the arcuate nucleus of hypothalamus when estrogen decreases during perimenopause are the key factors that trigger hot flashes. Some scholars believe that KNDy neurons in the arcuate nucleus are involved in the occurrence of hot flashes by regulating the pulse release of gonadotropin-releasing hormone and its downstream luteinizing hormone, while some other scholars believe that KNDy neurons in the arcuate nucleus play a key role in the process of hot flashes by regulating the median preoptic nucleus of the hypothalamic preoptic area. Therefore, this review intends to summarize the above two types of current relationship between the KNDy neurons in the arcuate nucleus and the occurrence of hot flashes and the possible mechanisms by which KNDy neurons participate in hot flashes, and lay a theoretical foundation for the exploring of new targets and method for the treatment of perimenopausal hot flashes.

Ziyuglycoside II inhibits the growth of digestive system cancer cells through multiple mechanisms / 中国天然药物

Digestive system cancers, including liver, gastric, colon, esophageal and pancreatic cancers, are the leading cause of cancers with high morbidity and mortality, and the question of their clinical treatment is still open. Previous studies have indicated that Ziyuglycoside II (ZYG II), the major bioactive ingredient extract from Sanguisorba officinalis L., significantly inhibits the growth of various cancer cells. However, the selective anti-tumor effects of ZYG II against digestive system cancers are not systemically investigated. In this study, we reported the anti-cancer effect of ZYG II on esophageal cancer cells (OE21), cholangiocarcinoma cells (HuCCT1), gastric cancer cells (BGC-823), liver cancer cells (HepG2), human colonic cancer cells (HCT116), and pancreatic cancer cells (PANC-1). We also found that ZYG II induced cell cycle arrest, oxidative stress and mitochondrial apoptosis. Network pharmacology analysis suggested that UBC, EGFR and IKBKG are predicted targets of ZYG II. EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYG II and both docking simulation and western blot analysis demonstrated that ZYG II was a potential EGFR inhibitor. Furthermore, our results showed synergistic inhibitory effects of ZYG II and chemotherapy 5-FU on the growth of cancer cells. In summary, ZYG II are effective anti-tumor agents against digestive cancers. Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYG II for the treatment of digestive system cancers.

Integrative lipidomic and transcriptomic study unravels the therapeutic effects of saikosaponins A and D on non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has become one of the most prominent causes of chronic liver diseases and malignancies. However, few therapy has been approved. Radix Bupleuri (RB) is the most frequently used herbal medicine for the treatment of liver diseases. In the current study, we aim to systemically evaluate the therapeutic effects of saikosaponin A (SSa) and saikosaponin D (SSd), the major bioactive monomers in RB, against NAFLD and to investigate the underlying mechanisms. Our results demonstrated that both SSa and SSd improved diet-induced NAFLD. Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes, like