This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

Cognitive dysfunction is the impairment of higher brain functions.Cognitive impairment caused by neuropsychiatric diseases has caused serious impact on patients'quality of life and the outcome of the disease.The transcranial alternating current stimulation(tACS)improves cognitive function by modulating neural oscillations of specific frequencies,affecting the release of neurotransmitters such as serotonin and dopamine,and enhancing local and distal synchronization of brain networks.Specific frequencies of tACS can improve the cognitive impairment caused by Alzheimer disease(AD),schizophrenia,and depression,among which the gamma and theta frequencies of tACS have the most significant effects on cognitive function.tACS has high safety and low operational difficulty,and has great potential to improve cognitive function.

Objective:To evaluate the efficacy and safety of traditional Chinese medicine(TCM)in the treatment of male im-mune infertility(MII)by meta-analysis.Methods:We retrieved randomized controlled trial(RCT)on the treatment of male im-mune infertility with traditional Chinese medicine from the databases of WanFang,Chinese Biomedical Literature,Cochrane Library,Weipu,PubMed and CNKI,and performed methodological quality assessment of the RCTs identified and statistical analysis and evalua-tion of the publication bias using the RevMan5.4 software.Results:Totally,25 RCTs(2 563 cases)were included in this study.Compared with Western medicine alone in the treatment of MII,TCM achieved a significantly higher total effectiveness rate(OR=6.35,95% CI:4.96-8.13,P<0.000 01),negative conversion rate of seminal plasma anti-sperm antibodies(OR=4.52,95% CI:2.72-7.51,P<0.000 01),negative rate of serum anti-sperm antibodies(OR=2.98,95% CI:2.23-3.96,P<0.000 01),sperm concentration(MD=15.56,95% CI:11.32-19.79,P<0.000 01),grade a sperm motility(MD=3.85,95% CI:1.91-5.79,P=0.000 01),grade a+b sperm motility(MD=13.77,95% CI:7.06-20.48,P<0.000 1),sperm viability(MD=10.32,95% CI:6.78-13.86,P<0.000 01)and pregnancy rate(OR=3.53,95% CI:2.68-4.63,P<0.000 01),but a lower rate of adverse reactions(OR=0.06,95% CI:0.01-0.23,P<0.000 01).There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII(MD=-7.53,95% CI:-15.50-0.44,P=0.06).Conclusion:TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

Glycine receptors (GlyRs) belong to the ligand-gated ion channel receptor superfamily and are widely distributed throughout the central nervous system. GlyRs are essential for maintaining visual, auditory, sensory and motor functions, and abnormalities in its structure and function can lead to various neurological disorders. This review aims to provide an extensive analysis of the structure, function and regulatory mechanisms of GlyRs, and evaluate its role in various central nervous system diseases. Ultimately, this review will provide theoretical support for the development of novel drugs specifically targeting GlyRs.
Receptors, Glycine/physiology* ; Humans ; Animals ; Central Nervous System Diseases/metabolism*

3D printing is an additive manufacturing technology with the help of digital control. Since FDA approved the first 3D printing drug in 2015, its research enthusiasm in the pharmaceutical field has been increasing year by year. In printing technology, fused deposition molding (FDM) and semi-solid extrusion (SSE) are the two most widely used extrusion molding technologies. In this review, recent advances of pharmaceutical 3D printing extrusion molding technology are reviewed from six aspects: mechanism, equipment, pharmaceutical excipients, applications, design and industrialization prospects of extrusion molding technology.

ObjectiveTo analyze the induction effect of Fusobacterium nucleatum （Fn） on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78（GRP78） and X-box binding protein 1（XBP1） in esophageal squamous cell carcinoma （ESCC）， and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h， 24 h and 48 h. The oxidative stress indexes （ROS， MDA and SOD） and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups， Fn+siNC1 groups， Fn+siGRP78 groups， Fn+siNC2 groups and Fn+siXBP1 groups； the oxidative stress indexes， paclitaxel （PTX） response efficacy， abilities of proliferation， invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells， the content of ROS and MDA was gradually increased， the activity of SOD was gradually decreased， and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups （12 h， 24 h and 48 h） （P < 0.05）. Compared with Fn groups， Fn+siNC1 groups， and Fn+siNC2 groups， ROS and MDA contents were decreased， SOD activity was increased， PTX response efficacy was enhanced， and abilities of proliferation， invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups （P < 0.05）. The rates of Fn， GRP78 and XBP1 in ESCC tissues were 43.16%， 69.66% and 60.68%， respectively. And the three indexes were significantly consistent （P < 0.05）. The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking， and the tumor differentiation degree was low， the invasion degree was deep， the lymph node metastasis rate was high， and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened （P < 0.05）. ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1， and promote the malignant evolution of ESCC.

Coronary Angiography ; Coronary Disease ; Humans ; Liver ; Non-alcoholic Fatty Liver Disease/complications*

Allyl alcohol is an intermediate widely used in industrial production activities, which has caused many occupational damage in China. In this paper, the data of a case of skin damage and clinical cure of inhalation pneumonia caused by occupational allyl alcohol exposure were analyzed and summarized. The patient accidentally inhaled large amounts of allyl alcohol at work and had skin exposure, which was mainly manifested as aspiration pneumonia, respiratory failure, eye damage and skin bullae. After short-term hormone shock therapy, mechanical ventilation, infection prevention, local treatment and other comprehensive treatment, the patient was clinically cured. This case suggests that chemical pneumonia and respiratory failure may be caused by inhalation of allyl alcohol, and skin bullae may be caused by skin contact. Early treatment and hormone use should be emphasized.
Blister ; Hormones ; Humans ; Pneumonia ; Propanols ; Respiratory Insufficiency

Objective:To observe the effect of forsythiaside A on gastrointestinal motility disorder induced by chemotherapy in mice， and explore the mechanism of forsythiaside A regulating gastrointestinal motility. Method:The 60 KM mice were randomly divided into normal group， model group， metoclopramide group （5 mg·kg^-1） and forsythiaside A low， medium and high-dose groups （30， 60， 120 mg·kg^-1）， 10 for each group， which include half male and half female. The above dose was given once a day for 4 consecutive days， which the intragastric volume was 10 mL·kg^-1. One hour after 1^rd day administration， equal volume of saline was intraperitoneally injected to the normal group， 2 mg·kg^-1 cisplatin was intraperitoneally injected to the other groups with daily for 4 consecutive days. Observing the effects of forsythiaside A on gastric emptying and small intestinal propulsion on mice models， serum gastrin （GAS） and somatostatin （SS）， motilin （MTL）， vasoactive intestinal peptide （VIP） levels were examined by enzyme-linked immunosorbent assay （ELISA）. Activities of acetylcholinesterase （AChE） and total nitric oxide synthase （tNOS） in gastric antrum and ileum were detected by ELISA. The expression of AChE and inducible nitric oxide synthase （iNOS） in gastric antrum and ileum were detected by Western blot. Result:Compared with normal group， the gastric retention rate and small intestinal propulsion rate of the model group were significantly increased （P<0.01）， serum levels of MTL， GAS， SS and VIP， the AChE activity in the homogenate of ileum in the model group were significantly reduced （P<0.05，P<0.01）， while the tNOS activities in gastric antrum and ileum were significantly increased （P<0.05，P<0.01）. Protein expression of AChE in gastric antrum and ileum were significantly decreased （P<0.05）， and the expression level of iNOS protein was significantly increased in the model group （P<0.05）. Compared with model group， different doses of forsythiaside A can reduce the gastric residual rate and small intestinal propulsion rate of mice to varying degrees. Meanwhile forsythiaside A can increase the serum levels of MTL， GAS， SS， and VIP， and the AChE activity and protein expression levels in gastric antrum and ileum tissues were also increased， while tNOS activity and iNOS protein expression were decreased in gastric antrum and ileum （P<0.05，P<0.01）. Conclusion:Forsythiaside A can significantly ameliorate the delayed gastric emptying and small intestine hyperfunction induced by cisplatin in mice. Its mechanism to ameliorate gastrointestinal dysfunction caused by chemotherapy is related to the regulation of gastrointestinal AChE and NOS activity in gastric antrum and ileum and the regulation of gastrointestinal hormone levels.