BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

Objective To investigate effect of cassava RS3 resistant starch(Ce-RS3)on serum homocysteine(Hcy)level in patients with atherosclerotic cerebral infarction(ACI)during the recovery period.Methods A total of 55 patients with ACI at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from October 2023 to October 2024 were selected as subjects.They were devieded into observation group(n=28)and control group(n=27)using a random number table.The control group received atorvastatin calcium,phospholipids,and aspirin,while the observation group received atorvastatin calcium,phospholipids,aspirin,and Ce-RS3.After 12 weeks of treatment,homocysteine(Hcy)levels,carotid plaque diameter,National Institutes of Health stroke scale(NIHSS)scores,Barthel index(BI)scores,and traditional Chinese medicine(TCM)syndrome scores were compared between two groups.Results After treatment,the serum Hcy levels decreased and carotid plaque size reduced in both groups,with the NIHSS scores and TCM syndrome scores also decreased,and observation group was lower than control group(P＜0.05).After treatment,the BI score increased,with observation group higher than control group(P＜0.05).Conclusion The use of Ce-RS3 in the recovery phase of patients with ACI can effectively improve neurological function and enhance treatment efficacy.

Objective To investigate effect of cassava RS3 resistant starch(Ce-RS3)on serum homocysteine(Hcy)level in patients with atherosclerotic cerebral infarction(ACI)during the recovery period.Methods A total of 55 patients with ACI at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from October 2023 to October 2024 were selected as subjects.They were devieded into observation group(n=28)and control group(n=27)using a random number table.The control group received atorvastatin calcium,phospholipids,and aspirin,while the observation group received atorvastatin calcium,phospholipids,aspirin,and Ce-RS3.After 12 weeks of treatment,homocysteine(Hcy)levels,carotid plaque diameter,National Institutes of Health stroke scale(NIHSS)scores,Barthel index(BI)scores,and traditional Chinese medicine(TCM)syndrome scores were compared between two groups.Results After treatment,the serum Hcy levels decreased and carotid plaque size reduced in both groups,with the NIHSS scores and TCM syndrome scores also decreased,and observation group was lower than control group(P＜0.05).After treatment,the BI score increased,with observation group higher than control group(P＜0.05).Conclusion The use of Ce-RS3 in the recovery phase of patients with ACI can effectively improve neurological function and enhance treatment efficacy.

ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg^-1）， valsartan capsule group （10.29 mg·kg^-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L^-1 glucose）， high glucose group （35 mmol·L^-1 glucose）， DMSO group （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS group （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.

ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg^-1）， and losartan capsules （10.29 mg·kg^-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L^-1）， high glucose （35 mmol·L^-1）， DMSO （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.

The pachychoroid spectrum disorders (PSD) refers to a group of clinical disorders characterized by common features of pathological choroidal thickening and potential pathogenic mechanisms. The pathological mechanism of PSD is very complex, and the theory of venous overload provides valuable research directions. The multimodal imaging technology represented by optical coherence tomography angiography has continuously evolved to provide clear and three-dimensional images of the fundus, making it easier to diagnose and monitor PSD at an early stage. There is no unified consensus on how to develop a treatment plan for PSD, and current research has shown that feasible treatments include drug therapy, laser photocoagulation therapy, and photodynamic therapy. However, the evidence of effectiveness and safety provided by these studies is still not sufficient. Surgery and integrative Chinese and Western medicine may provide new prospects for the treatment of PSD. In the future, it is necessary to further develop reasonable research programs, expand the sample size, strengthen follow-up observation, and provide more safe and effective treatment programs for patients.

Objective:To explore the related risk factors for systemic embolism (SE) in patients aged≥75 years with non-valvular atrial fibrillation (NVAF).Methods:A case-control study. NVAF patients aged≥75 years who were hospitalized at the First Affiliated Hospital of Xinjiang Medical University from October 2018 to October 2020 were divided into no SE ( n=1 127) and SE ( n=433) groups according to the occurrence of SE after NVAF. Multivariate logistic regression was used to analyze SE-related factors in patients with NVAF without anticoagulation treatment. Results:In the multivariate model, the following factors were associated with an increased risk of SE in patients with NVAF: history of AF≥5 years [odds ratio ( OR)=2.75, 95% confidence interval ( CI) 1.98-3.82, P<0.01], lipoprotein(a)>300 g/L ( OR=2.07, 95% CI 1.50-2.84, P<0.01), apolipoprotein (Apo)B>1.2 g/L ( OR=1.91, 95% CI 1.25-2.93, P=0.003), left ventricular ejection fraction (LVEF) of 30%-49% ( OR=2.45, 95% CI 1.63-3.69, P<0.01), left atrial diameter>40 mm ( OR=1.54, 95% CI 1.16-2.07, P=0.003), and CHA 2DS 2-VASc score≥3 ( OR=15.14, 95% CI 2.05-112.13, P=0.01). ApoAI>1.6 g/L was negatively correlated with the occurrence of SE ( OR=0.28, 95% CI 0.15-0.51, P<0.01). Conclusions:History of AF≥5 years, lipoprotein(a)>300 g/L, elevated ApoB, left atrial diameter>40 mm, LVEF of 30%-49%, and CHA 2DS 2-VASC score≥3 are independent risk factors for SE whereas ApoAI>1.6 g/L is a protective factor against SE in patients with NVAF.

LC3-associated phagocytosis (LAP) is a special phagocytosis occurring at the intersection of the two pathways of phagocytosis and autophagy. A hallmark event of the LAP process is the recruitment of microtubule-associated proteinⅠlight chain type 3-Ⅱ(LC3Ⅱ) to the phagosome surface of the monolayer membrane structure. The LAP pathway relies on the functions of the RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein (Rubicon) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The LC3-associated phagosome (LAPosome) binds to the lysosome to digest and degrade the contents. In recent years, increasing studies have found that LAP plays an important role in the infections caused by pathogenic microorganisms including fungi and bacteria. LAP is a crucial way in the host to resist and degrade the infection of pathogenic microorganisms. However, some pathogenic microorganisms can effectively escape from LAP in the host and even use LAPosome as a place for colonization and replication. This article summarized the recent progress in the role of LAP in host defense against pathogenic microorganism infection and the significance of it in the occurrence and development of diseases.

Objective: To observe the clinical efficacy of umbilical therapy with herbal cakes made of Ge Gen Qin Lian Tang prescription of different dosages in treating damp-heat diarrhea in young children. Methods: Seventy-two kids with diarrhea of damp-heat pattern were recruited and divided into a high-dosage group and a low-dosage group using the random number table method, with 36 cases in each group. They all received conventional antidiarrheal treatment and umbilical application with herbal cakes. However, the herbal cakes for the high-dosage group were made of the mixture of Ge Gen Qin Lian Tang powder and water, and those for the low-dosage group consisted of 10％ Ge Gen Qin Lian Tang powder and 90％ auxiliary materials (corn starch) plus water. The treatment duration was 3 d. The clinical efficacy, antidiarrheal rate, effective rate for symptoms and signs of traditional Chinese medicine (TCM), TCM symptoms score, and safety indicators were compared between the two groups. Results: After the treatment, the TCM symptoms scores dropped significantly in both groups (P<0.01) and were lower in the high-dosage group than in the low-dosage group (P<0.05). The clinical efficacy was more significant in the high-dosage group than in the low-dosage group after the treatment, and the between-group difference was statistically significant (P<0.05); the antidiarrheal rate was markedly higher in the high-dosage group than in the low-dosage group (P<0.05). Regarding the TCM symptoms and signs, the high-dosage group showed better results in improving the greasy and yellowish tongue coating, bowel movement frequency, watery excrement, short and dark urine, red tongue body, red anus, vomiting, bowel sounds, and abdominal bloating compared with the low-dosage group, and the between-group differences were statistically significant (P<0.01). Conclusion: Umbilical therapy with herbal cakes made of Ge Gen Qin Lian Tang is safe, reliable, and effective in treating damp-heat diarrhea in young children; the high-dosage herbal cakes produce more significant efficacy than the low-dosage ones and are worth further investigation.