OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

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.

Chronic heart failure （CHF） and diabetes mellitus （DM） comorbidity presents a myriad of symptoms and a complex pathogenesis， making the traditional diagnostic and treatment model of "using disease to treat syndrome" often inadequate in clinical practice. The concept of "syndrome-based treatment of disease" is rooted in the core thinking of traditional Chinese medicine （TCM） syndrome differentiation and treatment， emphasizing the importance of syndrome as the guiding principle. This approach categorizes various diseases according to their corresponding syndrome categories for exploration， adhering to the principle of starting from the syndrome and addressing the disease thereafter， which highlights the advantages of TCM holistic view and syndrome differentiation and treatment. The pathogenesis of CHF is characterized by deficiency of both Qi and Yin， along with blood stasis， affecting organs such as the lung， spleen， and kidney， which in turn impacts the distribution and metabolism of body fluids. Dysfunction in body fluid regulation leads to stagnation， resulting in pathological products like phlegm and turbidity， which exacerbates syndromes of Yin deficiency and excessive heat. As the conditions of Yin deficiency and dryness-heat intensify， and as body fluid depletion continues， the patient's DM symptoms worsen， contributing to or aggravating the comorbidity. Following the diagnostic approach of "syndrome-based treatment of disease"， TCM diagnosis and treatment of CHF and DM comorbidity should focus on the core pathogenesis of "deficient Qi retention". This study categorized CHF and DM comorbidity into four stages： A （comorbid risk period）， B （precomorbid period）， C （intermediate stage of comorbidity）， and D （advanced comorbidity）， proposing corresponding TCM syndrome types for each stage. In terms of treatment， adhering to the principle of "tonifying deficiency and relieving stagnation"， the specific methods included invigorating Qi and strengthening the body， nourishing Yin and generating body fluids， activating blood circulation and Qi， and promoting diuresis and removing toxins. This study reviewed recent research progress on Chinese medicine compound prescriptions for CHF combined with DM， aiming to achieve precise treatment for both diseases and provide a scientific basis for the application of TCM in the prevention and treatment of CHF and DM comorbidity.

ObjectiveTo observe the clinical efficacy and relative mechanism of the Modified Wenshen Yixin Formula （温肾益心方加减， MWYF） as an auxiliary treatment of coronary heart disease （CHD） complicated with hypothyroidism of spleen-kidney yang deficiency. MethodsA total of 135 CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency were included and divided into control group （67 cases） and experimental group （68 cases） according to the patients' wishes of herbal medicine administration. The control group was given conventional western medicine， while the treatment group was additionally given MWYF， 1 dose per day； both groups were treated for 8 weeks. The traditional Chinese medicine （TCM） syndrome scores， angina scores， SF-36 scores， thyroid function indicators including thyroid stimulating hormone （TSH）， thyroxine （T4） and triiodothyronine （T3）， as well as serum cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， monocyte chemoattractant ligand 2 （CCL2）， and tumor necrosis factor-related activator protein （CD40L） levels before and after treatment were compared between the two groups. The dosage and reduction and discontinuation rate of thyroid hormone preparations after treatment were compared between the two groups. The effectiveness regarding TCM syndrome and angina pectoris was evaluated， and the safety was assessed. ResultsBias was adjusted by matching on propensity score， and 102 cases were finally included in the statistical analysis， with 51 cases in each group. The total effective rate regarding TCM syndrome ［94.12% （48/51） versus 64.71% （33/51）］， the total effective rate regarding angina pectoris ［80.39% （41/51） versus 62.75% （32/51）］， and the reduction and discontinuation rate of thyroid hormone preparation ［39.21% （20/51） versus 5.88% （3/51）］ were significantly higher in the experimental group than those in the control group （P＜0.05 or P＜0.01）. After treatment， the total TCM syndrome score， individual scores of major symptoms ， the major symptoms score， the secondary symptoms score， angina pectoris score， and TSH level were significantly reduced （P＜0.01）， while all dimensions of SF-36 scores， T4， T3， and cAMP levels significantly increased in both groups （P＜0.05 or P＜0.01）. The dosage of thyroid hormone preparations and the levels of cGMP， CCL2， and CD40L in the experimental group significantly decreased after treatment （P＜0.01）. When compared between the two groups after treatment， the total TCM syndrome score， the major symptoms score， the scores of individual major symptom （chest tightness， chest pain， fear of cold， cold limbs， waist and kness soreness and weakness）， the secondary symptoms score， angina pectoris score， TSH， cGMP， CCL2， and CD40L levels of the experimental group were significantly lower than those of the control group （P＜0.05 or P＜0.01）， while all dimension scores of SF-36， T4， T3， and cAMP levels were significantly higher （P＜0.01）. A total of three adverse events occurred during treatment， none of which were judged to be related to the interventions of this study. ConclusionMWYF can significantly ameliorate the TCM syndrome， angina pectoris， quality of life and thyroid function in CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency， and can promote the reduction and disconti-nuation of thyroid hormone preparations. The mechanism may be related to the regulation of cAMP/cGMP balance， the regulation of hypothalamic-pituitary-thyroid metabolic axis and the reduction of immune inflammation.

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Abstract: Stem cells, which are a type of primitive cells with multipotent differentiation potential and self-renewal ability, have the potential to regenerate various tissues and organs. Stem cell drug development is a frontier research field in life sciences. Extensive clinical trials involving stem cells have been conducted for different complicated diseases. Some stem cells have been approved as drugs for some indications, indicating their broad industrial prospects. This review introduces the progress of stem cell drugs around the world, especially in China, and discusses the main problems in the industrialization of stem cell drugs, such as their effectiveness, quality control and safety, so as to provide some reference and insight for the development and rapid industrialization of stem cell drugs.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

This paper summarized Professor ZHANG Junping's clinical experience in treating coronary heart disease （CHD） combined with hypothyroidism. It is believed that yang deficiency was the root cause of CHD complicated with hypothyroidism， and also the key pathogenesis throughout its development. Accordingly， combined with the different focuses on the lesions in the blood， pulse， heart and spirit， Professor ZHANG took warming yang as the basic rule and summarized the four methods of warming yang for syndrome differentiation and treatment. When spleen-kidney yang deficiency， disturbance of qi transformation， dysfunction of blood transportation as the pathological basis of CHD combined with hypothyroidism， the self-prescribed Butian Formula （补天方） could be used for warming yang and benefiting the kidney， thereby regulating Qi and blood； when the cold and dampness blocked the blood vessels， and turbidity-toxin generated gradually， resulting in heart vessel obstruction， the self-prescribed Huazhuo Changmai Decoction （化浊畅脉汤） could be used to warm yang and dissolve the turbidity so that to unblock the heart vessels； when the structure and function of the heart fail， edema due to yang deficiency with pericardial fluid retention， the self-prescribed Yuxin Baomai Formula （育心保脉方） could be used to warm yang and excret water， and protect the heart； when yang deficiency led to emotional and mental stagnation， and the heart impairment aggravated emotional and mental disorders， which resulted in emotional and mental abnormalities， the self-prescribed Jieyu Anshen Decoction （解郁安神汤） could be used to relieve emotional and mental stagnation， and calm mind.

Objective To investigate the expression of miR-31a-5p in myocardial infarction (MI) mice and its potential mechanism. Methods A dataset was downloaded from the gene expression database, and miR-31a-5p and its predicted target gene hypoxia-inducible factor-1α (HIF-1α) were screened using bioinformatics methods. The MI model was established by ligating the left anterior descending branch of the coronary artery in C57BL/6J male mice which were randomly divided into sham and MI groups (n=6 in each group). The in vitro hypoxic cell model was induced by treatment of H9c2 cells with cobalt chloride (CoCl2) and divided into a control group, a model group, a NC group, a miR-31a-5p mimic group and a miR-31a-5p inhibitor group. The degree of myocardial tissue fibrosis was stained by Masson and analyzed. The expression levels of miR-31a-5p and HIF-1α mRNA in mouse myocardial tissues and H9c2 cells were detected by qRT-PCR. Western blotting was used to detect the expression levels of B-cell lymphoma 2 (Bcl-2), cleaved-caspase 3 apoptotic protein in mouse myocardial tissues and HIF-1α and apoptotic protein in H9c2 cells, respectively. The dual luciferase reporter gene assay was used to verify the targeting relationship between miR-31a-5p and HIF-1α. Results Masson staining showed significantly increased fibrosis in MI mice (P<0.000 1); miR-31a-5p, cleaved-caspase 3 were significantly elevated and Bcl-2 was decreased in MI mice and CoCl2 treated H9c2 (P<0.05). The results of dual luciferase reporter assay showed that the relative luciferase activity of miR-31a-5p mimic cotransfected with HIF-1α-3'-UTR WT plasmid was reduced (P<0.000 1); miR-31a-5p mimic decreased HIF-1α expression and increased apoptotic protein levels in CoCl2 induced H9c2 cells (both P<0.05), while miR-31a-5p exerted the opposite effect. Conclusion miR-31a-5p can aggravate apoptosis in myocardial ischemia by targeting HIF-1α.

Glycosylation is one of the most important reactions in living organisms as it results in the formation of glycoconjugates with diverse biological functions. Sugar nucleotides are structurally composed of sugar and nucleoside diphosphate or monophosphate, which are widespread within a variety of biological cells. As glycosyl donors for the transglycosyl reactions catalyzed by Leloir-type glycosyltransferases, sugar nucleotides are essential for the synthesis of glycans and glycoconjugates. However, high costs and limited availability of nucleotide sugars prevent applications of biocatalytic cascades on an industrial scale. Therefore, attentions on synthetic strategies of sugar nucleotides have been increasing to achieve their wide applications in various fields. The 9 common sugar nucleotides in mammals have been fully studied with large-scale synthesis through chemical, enzymatic (chemo-enzymatic) and cell factory strategies. In addition to common sugar nucleotides, many rare sugar nucleotides are present in plants and bacteria. Although unnatural sugar nucleotides cannot be synthesized in organisms, they have great potential in research as substrates for glycosyltransferases in carbohydrate synthesis, as enzyme inhibitors in biochemical studies, and as components of glycoconjugate biosynthesis. Therefore, increasing attention has been paid to explore the efficient synthesis of unnatural sugar nucleotides. Currently, strategies for chemical synthesis of sugar nucleotides have been greatly improved, such as the use of effective catalysts for forming pyrophosphate bonds and the development of entirely new synthesis protocols. Multiple sugar nucleotides, especially unnatural sugar nucleotides, are synthesized chemically. However, chemical synthesis requires tedious protection and deprotection steps, resulting in complex steps, high cost and low yield. In contrast, enzymatic (chemo-enzymatic) and cell factory methods have significant advantages such as high yield, easy operation and easy process scale-up in the preparation of sugar nucleotides. Hence, they are prominent strategies for sugar nucleotide preparation. Herein, the biosynthesis and application of sugar nucleotides are reviewed, mainly focusing on the 9 sugar nucleotides common in mammals. The early strategies for enzymatic synthesis of sugar nucleotides generally used de novo synthesis pathway. With the discoveries of enzymes involved in salvage pathway of sugar nucleotide synthesis and the development of one-pot multienzyme (OPME) method, the synthesis of sugar nucleotides was greatly simplified. Cell factory method employs the microbial living cells as a “processing plant” by engineering their metabolic pathways through genetic engineering technology. The cell factory method has high yield, and has been applied for efficient synthesis of several sugar nucleotides. Moreover, the strategy of gram-scale synthesis of multiple rare sugar nucleotides by cascade reactions from common sugar nucleotides using sugar nucleotides synthases cloned from different sources was illustrated. In recent years, the synthesis cost of sugar nucleotides has been further reduced through various ways, such as regeneration of nucleotides, regeneration of organic cofactors, and application of immobilized enzyme technology. Furthermore, through the continuous improvement of sugar nucleotide purification process, the use of high concentration of multi-enzyme cascade and rapid non-chromatographic purification process, the synthesis of multiple sugar nucleotides and their derivatives from monosaccharides was achieved, which gradually broke the limitations of the existing strategy. With the efficient synthesis of sugar nucleotides, their applications in various fields have been increasingly explored, including the synthesis of glycans and glycoconjugates, biochemical characterization of glycosyltransferases and bioorthogonal labeling strategies, which are of great significance to the research of biochemistry, glycobiology and the development of related pharmaceutical products.