ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism* ; Humans ; Central Nervous System/metabolism* ; Animals

OBJECTIVE To explore the clinical effect and safety of nicorandil combined with different doses of tirofiban in the treatment of elderly patients with acute ST-segment elevation myocardial infarction （STEMI）. METHODS A total of 162 elderly patients with STEMI admitted to our hospital from June 1， 2022 to June 1， 2024 were retrospectively enrolled. All patients received percutaneous coronary intervention （PCI） and conventional treatment of STEMI， and used nicorandil （5 mg each time， tid） and tirofiban. According to the use of tirofiban， the patients were divided into conventional-dose group （n＝104） and half-dose group （n＝58）. Patients in the conventional-dose group received an intracoronary injection of 10 μg/kg tirofiban， followed by intravenous infusion of 0.1 μg/（kg·min） for 48 h； patients in the half-dose group received an intracoronary injection of 5 μg/kg tirofiban， followed by intravenous infusion of 0.05 μg/（kg·min） for 48 h. Related indexes of PCI （the proportion of patients with grade 3 of thrombolysis in myocardial infarction， no reflow in infarct related artery， percentage decrease in total ST-segment elevation ＞50% on electrocardiogram 2 hours after PCI）， cardiac function parameters before and after treatment （troponin I， N-terminal pro-brain natriuretic peptide contents and left ventricular ejection fraction）， bleeding events during treatment （gingival bleeding， epistaxis， mucosal bleeding， gastrointestinal bleeding） and other adverse events （all-cause death， non-fatal reinfarction， hypotension， ventricular fibrillation， acute heart failure） were compared between 2 groups. RESULTS There were no significant differences in related parameters of PCI， cardiac function parameters after treatment， the incidences of gingival bleeding， epistaxis and gastrointestinal bleeding， the total incidence of bleeding events， or the incidence of other adverse events during treatment between 2 groups （P＞0.05）， but the incidence of mucosal bleeding in the conventional-dose group was significantly higher than the half-dose group （P＜0.05）. CONCLUSIONS The clinical effect of nicorandil combined with half-dose tirofiban in the treatment of elderly patients with acute STEMI is comparable to that of nicorandil combined with conventional dose of tirofiban， but the mucosal bleeding risk of the former is lower than that of the latter. Therefore， patients at risk of mucosal bleeding are more suitable to use the previous regimen.

Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a critical suppressor through transcriptomic sequencing and metastasis correlation screening. In UM, hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly alleviated by its overexpression. Mechanistically, UBE2G2 directly binds to galectin 3 binding protein (LGALS3BP) and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. Furthermore, UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and reprogramming the tumor microenvironment. Therefore, targeting intercellular and intracellular molecular mechanisms of the hypoxia-UBE2G2-LGALS3BP axis may contribute to developing various therapeutic strategies for UM.

Objective:To analyze the clinical application of different diagnostic methods for heart failure with preserved ejection fraction (HFpEF) in maintenance hemodialysis (MHD) patients.Methods:It was a single-center retrospective cohort study. Uremia patients who underwent hemodialysis at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2020 to June 2021 were enrolled. The demographic characteristics, laboratory indicators, and echocardiography parameters were collected. The 2016 European Society of Cardiology (ESC) criteria, H 2FPEF score [composite score based on weighted scores of heavy (H), hypertensive (H), atrial fibrillation (F), pulmonary hypertension (P), elder (E), and filling pressure (F)], and Heart Failure Association (HFA) -PEFF score [including pre-test assessment (P), echocardiography and natriuretic peptide score (E), functional testing (F) and final aetiology (F)] were used to diagnose HFpEF, respectively, and the difference of three diagnostic methods was compared. The association between HFpEF diagnosed by the three methods and poor outcomes (all-cause death, cardiovascular death) was analyzed. Results:A total of 160 MHD patients were included, whose age was (58.5±13.4) years, median dialysis age was 5.0 (2.3, 9.6) years, median H 2FPEF score was 2 (1, 3), median HFA-PEFF score was 4 (3, 5), and 92 (57.5%) were males. Of these patients, 118 patients (73.8%) met the 2016 ESC criteria for diagnosis of HFpEF, 4 (2.5%) met H 2FPEF score for diagnosis of HFpEF, and 56 (35.0%) met HFA-PEFF score for diagnosis of HFpEF. The consistency of three methods in diagnosing HFpEF was poor with κ values of 0.018 between ESC criteria and H 2FPEF score, 0.322 between ESC criteria and HFA-PEFF score, and 0.056 between H 2FPEF score and HFA-PEFF score. After a median follow-up of 2.6 years, 20 (12.5%) of the 160 MHD patients died. The Kaplan-Meier survival analysis showed a significant difference in mortality between patients diagnosed with HFpEF and those without using the H 2FPEF score (Log-rank test, χ2=6.95, P=0.008). After adjusting for demographic and clinical parameters, multivariate Cox regression analysis showed that HFpEF diagnosed by HFA-PEFF score was associated with all-cause mortality ( HR=2.73, 95% CI 1.07-6.98, P=0.036) and cardiovascular mortality ( HR=4.77, 95% CI 1.31-17.30, P=0.018). Conclusions:The 2016 ESC criteria, H 2FPEF score, and HFA-PEFF score have high heterogeneity and poor consistency in diagnosing HFpEF in MHD patients. Among the three diagnostic methods, only the diagnosis based on HFA-PEFF score is associated with the prognosis of MHD patients. The HFA-PEFF score can be used to assess the risk of HFpEF in MHD patients, and more clinical studies are needed to further verify it in the future.

In order to meet the fertility needs of infertile patients as much as possible during the pandemic of COVID-19 Omicron strain, this expert group reviewed global and domestic literature, combined with the current epidemic situation and prevention and control policies, fully considered the service procedures and characteristics of assisted reproductive institutions and sperm banks in China, and then put forward specific recommendations on institutional prevention and control management, and treatment and surgical management of COVID-19 infected patients, so as to guide and standardize the related practices in assisted reproductive institutions and sperm banks. In the practical application process, assisted reproductive institutions and sperm banks in various provinces and cities should develop personalized institutional prevention and control measures and patient management procedures based on local prevention and control requirements and the actual situation of their own institutions.

In order to meet the fertility needs of infertile patients as much as possible during the pandemic of COVID-19 Omicron strain, this expert group reviewed global and domestic literature, combined with the current epidemic situation and prevention and control policies, fully considered the service procedures and characteristics of assisted reproductive institutions and sperm banks in China, and then put forward specific recommendations on institutional prevention and control management, and treatment and surgical management of COVID-19 infected patients, so as to guide and standardize the related practices in assisted reproductive institutions and sperm banks. In the practical application process, assisted reproductive institutions and sperm banks in various provinces and cities should develop personalized institutional prevention and control measures and patient management procedures based on local prevention and control requirements and the actual situation of their own institutions.

OBJECTIVE To learn from the self-medication tax system in Japan and improve over-the-counter drug cost sharing mechanism in China. METHODS By searching relevant policies and literature ，the evolution ，specific contents ，current situation and effects of Japanese self-medication tax system were summarized. Recommendations were put forward in the light of the actual situation of over-the-counter drug guarantee in China. RESULTS & CONCLUSIONS Japan has implemented the self-medication tax system since 2017. The Ministry of Health ， Labour and Welfare has made clear provisions on the preconditions for applying for the tax system and the deduction standards of the tax system ，and established a list of drugs to be responsible for the regular inclusion and discharge of the drugs under the tax system. The self- medication tax system has a remarkable effect in promoting the self-health management ，disease prevention and reducing medical expenses of Japanese residents. Our country can learn from the self-medication tax system in Japan and the experience of implementing the special deduction system for major medical conditions in China. To promote rational self-medication ，it is advisable to add a special deduction system for over-the-counter drugs into deductions in personal income tax and formulate the criteria and scope of application ，and establish a special list of over-the-counter drugs，thereby reducing the heavy burden of medical expenses of residents ，and exploring a new way to share the costs of over-the-counter drugs which is applicable to our national conditions.

Secondary hyperparathyroidism (SHPT) is a common and serious complication in long-term dialysis patients, who often experience multiple symptoms and a poor quality of life. Parathyroidectomy (PTX) is the best choice for severe SHPT patients with poor drug treatment. At present, the follow-up after PTX has not received sufficient attention, and the assessment of patients' clinical symptoms and quality of life is not yet adequate. In view of this, we systematically combed the changes and influencing factors of patients' quality of life and related symptoms after surgery, in order to provide reference for the practice and research of symptom management of such patients in the future.