cAMP response element binding protein (CREB) is an eukaryotic intranuclear protein widely expressed in a variety of organs, and its activation increases the transcriptional activity of downstream genes and promotes the expression of related genes. The neuronal function of CREB is related to many intracellular processes, such as proliferation, differentiation, survival, long-term synaptic potentials, neurogenesis and neuronal plasticity. Increasing evidence has demonstrated that CREB plays an important role in the stroke development and therefore, it may serve as a potential target for stroke therapy. Since some herbal medicines as well as their active ingredients regulate the CREB signaling, this article will summarize the role of CREB signaling pathway in stroke pathophysiology. The research progress of traditional Chinese medicine and its active ingredients modulating CREB activity will also be discussed, with the aim of providing the basis and reference for the future research and development of natural medicines against stroke.

Diabetes mellitus is a metabolic disease with high incidence and many complications,among which type 2 diabetes mellitus(T2DM)accounts for a large proportion.Current studies have shown that T2DM is accompanied by damage of liver,kidney,and other organs and its complications seriously en-danger human health.Ferroptosis generates many Reactive Oxygen Species(ROS)through the Fenton reaction,and the accumulation of ROS activates Hypoxia Inducible Factor-1(HIF-1α).As a result,the level of vascular endothelial growth factor(VEGF)is increased.Ferrostatin-1(Fer-1),a ferroptosis in-hibitor,has strong antioxidant capacity.Therefore,based on the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)signaling pathway,we explored the therapeutic effect of Fer-1 on the liver and kidney tissues of diabetic mice.db/db mice(21～22 weeks old)were used as the model of diabetes mellitus.Ferroptosis inhibitor Fer-1 was used as the intervention drug.db/m mice served as the blank control group,and body weight and blood glucose were measured for 4 weeks.Food intake and water intake were recorded in each group.The levels of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in the serum were measured.ROS and Glutathione(GSH)activity in liver and kidney tissues and urinary protein content were measured.Liver and kidney tissue sections were stained with Hematoxylin-Eosin(HE),and the pathological morphology was observed under a light microscope.The protein levels of HIF-1α,VEGF,and glutathione peroxidase 4(GPX4)in liver and kidney tissues were detected by Western blot.In db/db mice,Fer-1(1 mg·kg-1,ig)could significantly reduce the a-mount of food and water intake,the levels of ALT and AST in serum,the ROS production in liver and kidney tissues,and the level of urine protein,but significantly increase the activity of GSH,thus improve the pathological conditions of liver and kidney.Fer-1 also significantly inhibited HIF-1α and VEGF pro-tein indexes and increased GPX4 protein levels in liver and kidney tissues.Although Fer-1 can not change the body weight and reduce blood glucose in diabetic mice,it can play a therapeutic role in the liver and kidney tissues of diabetic mice in the middle and late stages,and its mechanism may be related to HIF-1α/VEGF and GPX4.

Objective:To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway.Methods:The expression levels of LMP1 protein,CD38 and the phosphorylation levels of p70S6K in EBV+and EBV-DLBCL cell lines were detected by Western blot.Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi.The expression of LMP1 gene was verified by RT-qPCR.The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot.Results:Compared with EBV-DLBCL cells,the expression of LMP1 was detected on EBV+DLBCL cells(P=0.0008),EBV+DLBCL cells had higher phosphorylation levels of p70S6K(P=0.0072)and expression levels of CD38(P=0.0091).Compared with vector group,the cells of LMP1OE group had higher expression levels of LMP1 and CD38(P=0.0353;P＜0.0001),meanwhile molecular p70S6K was phosphorylated much more(P=0.0065);expression of LMP1 mRNA was verified(P＜0.0001).Compared with si-NC group,expression level of LMP1 protein(P=0.0129)was not detected and phosphorylated p70S6K disappeared of LMP1KO group(P=0.0228);meanwhile,expression of CD38 decreased,although there was no significant difference(P=0.2377).Conclusion:LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.
Infant, Newborn ; Humans ; Hypothermia, Induced/methods* ; Hypothermia/therapy* ; Hyperbaric Oxygenation ; Brain ; Electroencephalography ; Hypoxia-Ischemia, Brain/therapy*

Objective:To study the prevalence and distribution of adult thyroid diseases in urban and rural areas of Hebei Province.Methods:A multi-stage stratified cluster sampling method was used to select Renqiu City and Licun Town, Luquan City of Hebei Province as the urban and rural survey sites, respectively. Questionnaire survey, physical examination and thyroid B ultrasound examination were conducted on local permanent residents (≥ 5 years of residencies) over 18 years old. The fasting venous blood sample was collected to determine the serum thyroid function indicaters.Results:A total of 2 650 adults were surveyed, including 1 393 urban residents and 1 257 rural residents (1 357 males and 1 293 females). A total of 435 patients with thyroid diseases were diagnosed, the detection rate was 16.42%. There were seven thyroid diseases, including subclinical hypothyroidism (60.92%, 265/435), Hashimoto's thyroiditis (34.02%, 148/435), hypothyroidism (4.83%, 21/435), simple goiter (3.22%, 14/435), hyperthyroidism (2.53%, 11/435), subclinical hyperthyroidism (2.53%, 11/435), and thyroid cancer (1.84%, 8/435). The detection rates of thyroid diseases in urban and rural areas were 21.18% (295/1 393) and 11.14% (140/1 257), respectively. The detection rates of thyroid diseases in males and females were 11.42% (155/1 357) and 21.66% (280/1 293), respectively. The detection rates of thyroid diseases in 18-< 30, 30-< 40, 40-< 50, 50-< 60 and ≥60 years old were 13.46% (91/676), 14.81% (81/547), 15.42% (89/577), 20.94% (85/406) and 20.05% (89/444), respectively. There were statistically significant differences between different areas, gender and age groups (χ 2 = 48.54, 50.53, 14.68, P < 0.05). Conclusions:The detection rate of subclinical hypothyroidism in adults in urban and rural areas of Hebei Province is relatively high, followed by Hashimoto's thyroiditis. Attention should be paid to the screening, evaluation, and intervention of thyroid function among urban female populations.

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.