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.

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.

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.

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 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 evaluate the short-term outcome of single stenting technique for unruptured, wide-necked, tiny aneurysms of the anterior circulation.

METHODSEleven unruptured, wide-necked, tiny aneurysms of the anterior circulation were treated by a single stent deployed in the parent artery between January 2008 and July 2013 in Department of Neurosurgery in Beijing Hospital. The maximum diameter of the aneurysms ranged from 2.0 to 3.0 mm, mean (2.4 ± 0.4) mm, and the dome-to-neck ratios were all ≤ 1.2. The locations were clinoid segment of internal carotid artery (n=2), posterior communicating artery origin (n=4), anterior choroidal artery origin (n=2) and middle cerebral artery bifurcation (n=3). All internal carotid aneurysms were located in the medial and/or ventral wall of the internal carotid artery. The rate of aneurysm obliteration and rupture during follow-up was obtained by repeat angiography and clinic or telephone interview respectively.

RESULTSSole stent placement in the parent artery was intentionally performed for nine aneurysms, while attempt of coiling after stent deployment for the other two aneurysms failed due to unsuccessful microcatherization. Ten stents were successfully deployed, of which one was used to treat two tandem lesions simultaneously. Only one aneurysm became smaller immediately postprocedure. No perioperative complications occurred. Angiographic follow-up after a mean period of (13 ± 6) months (range 8-24 months) revealed that 8 aneurysms did no change in size, 2 became smaller and only one was totally occluded. Asymptomatic in-stent stenosis of the parent artery was found in all 3 shrinking or occluded aneurysms. No aneurysm rupture was observed in the clinical follow-up.

CONCLUSIONFor those unruptured, wide-necked, tiny aneurysms arising at branching sites in the anterior circulation, single stenting technique seems to be a safe alternative treatment, while the short-term rate of aneurysm occlusion is low.

Aneurysm, Ruptured ; Beijing ; Cardiovascular Surgical Procedures ; methods ; Carotid Artery Diseases ; surgery ; Carotid Artery, Internal ; pathology ; Cerebral Angiography ; Constriction, Pathologic ; Humans ; Intracranial Aneurysm ; surgery ; Stents ; Treatment Outcome

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.

Objective To investigate the clinical effect and feasibility of interventional treatment of cervical artery stenosis in the elderly patients aged 75 years and over. Methods The data of 60cases aged 75 years or over who underwent interventional treatment of the cervical arteriostenosis involving carotid artery (CA), vertebral artery (VA) or proximal segment of the subclavian artery (SCA) were analyzed retrospectively. The clinical manifestations, imaging characteristics,interventional managements and follow-up results were recorded. Results In this cohort, the mean age was (78. 9±3.7) years (range from 75 to 89). The 50 patients (93.3%) complained of cerebral ischemic symptoms, and all the patients had concurrent diseases or risk factors, including hypertension, diabetes mellitus, coronary heart disease (CHD), stroke history, and so on. Digital subtraction angiography (DSA) data showed 55 cases (91.7%) had 2 or more cerebral arteries with a stenosis exceeding 30%. Among all cases, 84 lesions were treated with 84 stents, with a technical success rate of 98.8%. After stenting, the percent diameter stenosis of lesions decreased from a mean of (80.8 ± 12.9) % to (7.1 ± 9.5 ) %. The periprocedural and 30-day postoperative neurological complication rate was 8. 3 %, resulting in a permanent complication rate of 5 %. Clinical improvement rate was 87.5%. During a follow-up period of (36.7±26. 3) months (range from 5 to 99), there were 4 deaths: 2 died from myocardial infarction, 1 died from brain metastases of lung cancer and 1 died from cerebral hemorrhage. Cerebral infarction recurred in 3 cases. Imaging follow-up in 78. 3% of patients for 66 stents, including ultrasound, CTA, MRA or DSA, showed that the general in-stent restenosis rate was 9. 1%, and the restenosis rate of VA, CA and SCA was 21.7% (5/23), 2.6%and 0, respectively. Conclusions The results of this series suggest that interventional treatment ofcervical artery stenosis in the elderly patients aged 75 years and over is effective and feasible. In our experience, clinical comprehensive management and skillful technique of the operator are equally important for the elderly patients aged 75 years and over with high incidence of concurrent diseases or risk factors.

Objective To explore the diagnosis, treatment strategies and clinical outcomes of spontaneous subarachnoid hemorrhage in elderly patients. Methods A total of 68 patients aged over 60 years presenting with spontaneous subarachnoid hemorrhage underwent cerebral angiography. And 72 intracranial aneurysms were detected in 60 patients, among whom 47 patients with 59 aneurysms underwent endovascular coil embolization, 6 aneurysms in 6 patients were clipped in microneurosurgery operation, and 7 patients chose conservative treatment. Results A total of 57 aneurysms (96.6%) were embolized successfully, among which 40 aneurysms (70.2%) reached dense occlusion and 17 aneurysms (29.8%) reached incomplete occlusion. Among 47 patients undergoing endovascular treatment, 39 patients (83.0%) were evaluated as good, 7 patients (14.9%) were moderately to seriously disabled according to Glasgow Outcome Scale when they were discharged, and one patient died. Conclusions Active treatment such as endovascular coil embolization can acquire good outcome in elderly patients with spontaneous subarachnoid hemorrhage, especially in elderly patients detected with aneurysms.

Objective To analyze the angiography procedure,distribution of cerebral vascular lesions and complications of cerebral angiography in patients 75 years or older with cerebrovascular diseases.Methods A total of 83 consecutive patients 75 years or older (range 75-89 years) diagnosed as cerebral vascular diseases underwent cerebral angiography with a coverage of all arteries supplying blood to the whole brain including bilateral subclavian arteries between June 2003 and June 2009.The angiogram showed 61 patients (73.5%) with ischemic cerebralvascular diseases,22patients (26.5%) with hemorrhagic cerebralvascular diseases.Results The 78 (94.0%)angiographies were performed using transfemoral access.Composite curve catheters such as Simmons curve were selected in 11 (13.3%) angiographies.In patients with ischemic cerebralvascular diseases,159 stenotic lesions were detected,among which 107 (67.3%) lesions located at the anterior circulation and 52 (32.7%) lesions located at the posterior circulation;97 (61.0%) lesions were extracranial and 62 (39.0%) lesions were intracranial.The 9 unruptured aneurysms were incidentally detected in 8 patients.In patients with hemorrhagic cerebralvascular diseases,19 aneurysms were detected in 16 (72.6 % ) patients.Complications occurred in 5 (6.0 % ) patients:transient neurological complications occurred in 2 (2.4%) patients,hematoma at the puncture site occurred in 2 (2.4%)patients and uroschesis occurred in 1 (1.2%) patients.Conclusions As a kind of diagnostic technology,cerebral angiography is safe in patients 75 years or older with cerebral vascular diseases.The incidence of complications especially permanent neurological complications is low.