In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Atherosclerotic cardiovascular disease(ASCVD)is one of the leading causes of death worldwide,and its progression is closely related to the pathological effects of neutrophil extracellular traps(NETs).In atherosclerosis(AS),NETs aggravate the process of disease by promoting inflammatory response,inducing endothelial dysfunction,promoting thrombosis and other mechanisms.The components such as myeloperoxidase(MPO),neutrophil elastase(NE)and citrullinated histone H3(CitH3)released by NETs can activate the immune inflammatory cascade,directly damage the vascular endothelium and promote thrombosis.In vascular inflammation,the formation of NETs is regulated by actin,and the released harmful molecules can induce endothelial cell apoptosis and drive the progress of inflammation through oxidative stress.The degradation and clearance of NETs depend on the action of enzymes such as deoxyribonuclease Ⅰ(DNase Ⅰ),and its regulatory mechanisms in atherosclerosis and vascular inflammation remain to be further studied.Based on the above mechanism,NETs-related markers have shown the potential as novel diagnostic and prognostic assessment biomarkers for ASCVD.This article aims to systematically elaborate the core pathological mechanism of NETs driving ASCVD through inflammatory activation,endothelial injury and thrombosis,providing a theoretical basis for targeted intervention.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Atherosclerotic cardiovascular disease(ASCVD)is one of the leading causes of death worldwide,and its progression is closely related to the pathological effects of neutrophil extracellular traps(NETs).In atherosclerosis(AS),NETs aggravate the process of disease by promoting inflammatory response,inducing endothelial dysfunction,promoting thrombosis and other mechanisms.The components such as myeloperoxidase(MPO),neutrophil elastase(NE)and citrullinated histone H3(CitH3)released by NETs can activate the immune inflammatory cascade,directly damage the vascular endothelium and promote thrombosis.In vascular inflammation,the formation of NETs is regulated by actin,and the released harmful molecules can induce endothelial cell apoptosis and drive the progress of inflammation through oxidative stress.The degradation and clearance of NETs depend on the action of enzymes such as deoxyribonuclease Ⅰ(DNase Ⅰ),and its regulatory mechanisms in atherosclerosis and vascular inflammation remain to be further studied.Based on the above mechanism,NETs-related markers have shown the potential as novel diagnostic and prognostic assessment biomarkers for ASCVD.This article aims to systematically elaborate the core pathological mechanism of NETs driving ASCVD through inflammatory activation,endothelial injury and thrombosis,providing a theoretical basis for targeted intervention.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Objective To observe the clinical efficacy of midnight-noon ebb-flow needling based on individualized timing in treating senile chronic gastritis. Method Seventy-eight elderly patients with chronic gastritis were randomized into a treatment group of 39 cases and a control group of 39 cases. The treatment group was intervened by midnight-noon ebb-flow needling based on individualized timing, while the control group was by midnight-noon ebb-flow needling based on local mean solar time, 10 d as a treatment course. The clinical efficacies were observed after 2 treatment courses. Result The total effective rate was 94.9% in the treatment group versus 89.7% in the control group, and the difference was statistically insignificant (P>0.05); the recovery rates were respectively 46.2% and 28.2%, and the difference was statistically significant (P<0.05). Conclusion Midnight-noon ebb-flow needling based on individualized timing can produce a significant efficacy in treating senile chronic gastritis, and is worth promoting in clinic.

OBJECTIVETo explore the feasibility, safety and efficacy of endovascular reconstructive treatment by multiple overlapping stents with or without coils.

METHODSTotally 17 patients of vertebrobasilar fusiform aneurysms treated by multiple overlapping stents with or without coils between September 2011 and September 2015 in Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. There were 15 male and 2 female patients with mean age of (47±13) years. Clinical manifestations included subarachnoid hemorrhage in 5 patients, cerebral ischemia or infarction in the posterior circulation in 5 patients, mass effect accompanied with brainstem infarction in 1 patients, headache or dizziness in 4, and incidental findings in 2 patients. Aneurysm located in intracranial vertebral artery in 11 patients, vertebrobasilar junction in 2 patients, and basilar trunk in 4 patients. Mean aneurysmal size was 18.5 mm×8.0 mm(length×width).

RESULTSSole stenting with overlapping stents was performed in 8 patients, and overlapping stents with coils was applied in 9 patients. Post-procedural hemorrhage occurred in a patient with a giant basilar trunk fusiform aneurysm and led to death. The 16 surviving patients were clinically followed up for a mean of 21.1 months. One patient had a modified Rankin score of 4, and the other patients had a good recovery. Among 15 patients with a mean angiographic follow-up of 8.6 months, 9 patients had their aneurysms further thrombosed, 3 patients were stable, and 3 patients with a recurred aneurysm. Final complete occlusion was achieved in 7 patients.

CONCLUSIONReconstructive treatment by overlapping stents with or without coils is feasible and relative safe in vertebrobasilar fusiform aneurysms.

Adult ; Endovascular Procedures ; Female ; Humans ; Intracranial Aneurysm ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Stents ; Subarachnoid Hemorrhage ; surgery ; Treatment Outcome ; Vertebral Artery ; pathology

Objective Toinvestigatethetechnicalfeasibilityandefficacyofvertebralarteryorigin and adjacent subclavian artery stenosis treated with a single self-expandable stent implantation simultaneously. Methods Twenty-onepatientswithposteriorcirculationischemicsymptomsweretreatedwithasingle stent implantation for vertebral artery origin (stenosis rate≥70%)and adjacent subclavian artery stenosis (stenosis rate ≥50%)simultaneously. The head end of a single self-expandable open-cell stent was implanted into the middle or distal V1 segment of vertebral artery,and the caudal end was implanted at the proximal subclavian artery during procedure. At 6 -12 months after procedure they received followed-up with CTA and/or DSA. The clinical and image data of the patients were analyzed retrospectively. Results Allstentswereimplantedsuccessfully.Thevertebralarterystenosisratewasdecreasedfrom 87. 1 ± 5. 7% before procedure to 7. 4 ± 6. 4% and the subclavian artery stenosis rate was decreased from 61.9±8.4% to4.5±5.7% aftertheprocedure.Therewassignificantdifference(allP<0.05).No perioperative complications occurred. The in-stent restenosis (about 50%) was found in one patient (4.8%)during the follow-up and he did not have any relevant clinical symptoms. One patient (4. 8%) had recurrent vertigo at 6 months after procedure. CTA and DSA examinations revealed stent compression and vertebralarteryocclusion.Conclusion Asingleself-expandablestentimplantationforthetreatmentof vertebral artery origin and adjacent subclavian artery stenosis simultaneously is feasible and safe. The incidences of in-stent stenosis and stent compression are low.