Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Coronary heart disease has a significant age correlation,and cell aging is the basic factor of aging of the body.Aging endothelial cells can interfere with the development of coronary heart disease through oxidative stress,mitochondrial dysfunction and other ways.This article focused on the mechanism of endothelial cell aging promoting coronary heart disease,which is related to"kidney"in TCM.Kidney has physiological characteristics such as participating in the growth and aging,the interaction of essence and blood,water and liquid metabolism,etc.Deficiency of kidney essence can slow down the generation of kidney turbidity,which can also be followed by blood stasis,phlegm and other pathogenic factors eroding arteries,which is consistent with the role of endothelial cell aging in promoting plaque development and accelerating thrombosis.The article also discussed the biological connotation of treating coronary heart disease from kidney from the perspective of endothelial cell aging,and put forward that the basic principle of treating coronary heart disease from kidney should be tonifying kidney and expelling turbidity,and then treat it according to different syndromes such as heart-kidney disharmony,qi stagnation in the heart and chest,phlegm obstruction in collaterals and blood stasis obstruction in collaterals,providing new ideas for the biological research and clinical application of TCM in the treatment of coronary heart disease.

Coronary heart disease has a significant age correlation,and cell aging is the basic factor of aging of the body.Aging endothelial cells can interfere with the development of coronary heart disease through oxidative stress,mitochondrial dysfunction and other ways.This article focused on the mechanism of endothelial cell aging promoting coronary heart disease,which is related to"kidney"in TCM.Kidney has physiological characteristics such as participating in the growth and aging,the interaction of essence and blood,water and liquid metabolism,etc.Deficiency of kidney essence can slow down the generation of kidney turbidity,which can also be followed by blood stasis,phlegm and other pathogenic factors eroding arteries,which is consistent with the role of endothelial cell aging in promoting plaque development and accelerating thrombosis.The article also discussed the biological connotation of treating coronary heart disease from kidney from the perspective of endothelial cell aging,and put forward that the basic principle of treating coronary heart disease from kidney should be tonifying kidney and expelling turbidity,and then treat it according to different syndromes such as heart-kidney disharmony,qi stagnation in the heart and chest,phlegm obstruction in collaterals and blood stasis obstruction in collaterals,providing new ideas for the biological research and clinical application of TCM in the treatment of coronary heart disease.

Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Objective To explore the effect of health education based on interactive 3D-modeling of intracranial artery on interventional diagnosis and treatment for patients with intracranial artery stenosis.Methods A total of 70 patients requiring interventional diagnosis and treatment due to intracranial artery stenosis admitted to our department in 2022 were enrolled,and randomly divided into observation group and control group,with 35 cases in each group.Their stenotic sites of intracranial arteries included the vertebral and middle cerebral arteries.The observation group received the preoperative conventional education mode combined with interactive 3D-modeling to carry out health education,while the control group got the unified education sheet and slides to carry out routine preoperative health education.A self-made publicity and education effectiveness rating scale was used to score before and after the publicity and education,and their scores of awareness of intracranial artery stenosis,awareness of treatment plans,and satisfaction with medical treatment were compared between the 2 groups.Results Before the health education,there was no statistical differences in their awareness scores concerning intracranial vessels(normal intracranial arteries,intracranial arterial occlusion,and vascular stenosis treatment)between the 2 groups patients.After the implementation of education,the awareness scores of intracranial vessels were elevated in both groups,but the awareness scores of the normal intracranial artery,intracranial artery occlusion,vascular stenosis treatment,and treatment satisfaction were significantly higher in the observation group than the control group(P＜0.05).Moreover,the patients with middle cerebral artery and vertebral artery stenosis from the observation group obtained obviously higher propaganda score than those from the control group(P＜0.05).Conclusion The health education model combined with 3D-modeling can improve the patient's awareness of the diagnosis and treatment of intracranial artery stenosis,promote their satisfaction of medical treatment,and thus increase their compliance and the rate of interventional diagnosis and treatment,and then finally,prevent strokes caused by intracranial artery stenosis.

OBJECTIVE To investigate the efficacy and safety of aerosol inhalation of polycolistin B in the treatment of severe pneumonia combined with mechanical ventilation， and to provide a reference of real-world data for clinical drug therapy. METHODS A retrospective cohort study was conducted to analyze the clinical data of 87 patients with severe pneumonia combined with mechanical ventilation at the First Affiliated Hospital of Shandong First Medical University from January 2021 to February 2023. According to route of administration， all patients were divided into combined group （24 cases， receiving aerosol YXH2021ZX013） inhibition of polycolistin B combined with intravenous dripping） and routine group （63 cases， intravenous dripping of polycolistin B alone）. The differences in efficacy （mortality，clinical response rate and bacterial clearance rate）and safety （elevated serum creatinine， bronchospasm and skin pigmentation） were compared between two groups； the influential factors of primary outcome index as mortality were analyzed through univariate analysis and multivariate Logistic regression analysis. RESULTS In terms of efficacy， there were no statistical differences in mortality（37.50% vs. 41.27%， P＝0.749）， clinical response rate （54.17% vs. 55.56%， P＝0.907） and bacterial clearance rate （45.83% vs. 44.44%， P＝0.907） between the two groups. In terms of safety， the incidence of bronchospasm in the combined group was significantly higher than that of the routine group （12.50% vs. 0， P＝0.028）， but the differences in incidence of elevated serum creatinine and skin pigmentation between two groups were not statistically significant （P＞0.05）. Univariate analysis showed that the moralities were higher in the case of infected with Acinetobacter baumannii， Klebsiella pneumoniae and combined use of quinolones （P＜0.05）； multivariate Logistic regression analysis showed that infection with A. baumannii （OR＝3.36， P＝0.014） and combined use of quinolones （OR＝3.54， P＝0.013） were independently associated with mortality （P＜0.05）. CONCLUSIONS For severe pneumonia patients with mechanical ventilation， intravenous dripping of polycolistin B combined with aerosol inhalation does not show superior efficacy compared with intravenous dipping of polycolistin B alone， but significantly increases the incidence of bronchospasm. Infection with A. baumannii and combined use of quinolones are independent risk factors for the increase of mortality.

Atherosclerotic cardiovascular disease is a common disease with high incidence rate and mortality worldwide. Atherosclerosis is an important pathological basis for the formation of ischemic cardiovascular diseases such as cardiovascular disease， which is related to inflammation， oxidative stress， apoptosis， vascular endothelial damage， foam cell formation， platelet activation， and so on， involving mitogen-activated protein kinase （MAPK）， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， cyclic adenosine monophosphate/protein kinase A （cAMP/PKA）， Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil containing protein kinase （ROCK）， nuclear factor-kappa B （NF-κB）， and other signaling pathways. In the past few decades， high-intensity statins were mainly used to treat atherosclerosis by reducing blood lipid levels， which usually caused obvious side effects. Therefore， the development of safer and more effective drugs and treatment modes is the focus of research at this stage. In recent years， Chinese medicine has been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. There are many studies on the mechanism of Chinese medicine in the prevention and treatment of atherosclerosis， and it is found that a variety of single Chinese medicine regulate the formation process of atherosclerosis by regulating targeted signal molecules. This paper reviewed the research results of related signaling pathways involved in the pathological formation of atherosclerosis and the mechanism of Chinese medicine in the prevention and treatment of cardiovascular diseases， thereby providing references for the clinical treatment of cardiovascular diseases.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Purpose: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. Materials and Methods: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. Results: One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). Conclusion The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.