Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

Objective:To study the therapeutic effect of sacubitril valsartan combined metoprolol on patients with chronic cardiac insufficiency and its impact on levels of chemokine CXC ligand 13(CXCL13)and human cardiac sarcoplasmic reticulum calcium ion ATPase 2a(SERCA2a).Methods:This randomized controlled study enrolled 120 patients with chronic cardiac insufficiency admitted in Peking University Shenzhen Hospital between June 2018 and December 2021.They were divided into control group(n=60,metoprolol therapy)and combined treatment group(n=60,additional sacubitril valsartan therapy based on control group).After 90d treatment,therapeutic effect,cardiac function,coronary hemodynamics,levels of CXCL13 and SERCA2a,and safety were compared between two groups.Results:Total effective rate in combined treatment group was significantly higher than that of control group(91.67％vs.76.67％,P=0.024).Compared with patients in control group after treatment,those in combined treatment group had significant higher left ventricular ejection fraction(LVEF),cardiac output(CO),coronary diastolic peak veloci-ty(DPV),systolic peak velocity(SPV),diastolic velocity time integral(DVTI),systolic velocity time integral(SVTI)and SERCA2a level,and significant lower left ventricular end-diastolic volume(LVEDV),left ventricular end-diastolic di-ameter(LVEDd)and CXCL13 level(P＜0.001 all).We detected no significant difference in incidence of adverse reac-tions between two groups during treatment(P=0.378).Conclusion:Sacubitril valsartan combined with metoprolol has good therapeutic effect in patients with chronic cardiac insufficiency.It can improve cardiac function,increase the coronary blood flow velocity,reduce CXCL13 level and increase SERCA2a level with good safety.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective To explore the efficacy of high tibial osteotomy(HTO)combined with medial meniscus centraliza-tion in knee osteoarthritis.Methods A total of 26 patients who underwent surgery from October 2018 to October 2020 were re-viewed.Among them,14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group,including 8 males and 6 females,with an average age of(50.2±1.4)years old and follow-up time of(16.8±4.0)months.Twelve patients with high tibial osteotomy were in the control group,including 6 males and 6 females,with an average age of(50.9±1.8)years and follow-up time of(19.0±4.8)months.Operation time,the knee Lysholm score,knee 2000 IKDC score,MRI,femoral tibial angle(FTA),hip knee ankle angle(HKA),and intraoperative and postoperative compli-cations were recorded.Results All the incisions healed without any complication.The operation time in the centralized group was longer than that in the control group[(65.0±2.1)min vs(52.0±2.1)min,P＜0.05].The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[(2.8±1.4)mm vs(1.1±2.2)mm,P＜0.05].The FTA,HKA,knee Lyshlom score,and 2000 IKDC score between two groups were no significantly(P＞0.05).Postop-erative knee Lyshlom score and knee 2000 IKDC score improved in both groups(P＜0.05).Conclusion HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function.The medium and long-term curative effect still needs long-term follow-up of more cases.

Objective To explore the postmortem diffusion rule of Aconitum alkaloids and their metabo-lites in poisoned rabbits,and to provide a reference for identifying the antemortem poisoning or post-mortem poisoning of Aconitum alkaloids.Methods Twenty-four rabbits were sacrificed by tracheal clamps.After 1 hour,the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration.Then,they were placed supine and stored at 25℃.The biological samples from 3 randomly selected rabbits were collected including heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney tissues at 0 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h after intragastric administration,respectively.Aconitum alkaloids and their metabolites in the biological samples were ana-lyzed by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Results At 4 h after intragastric administration,Aconitum alkaloids and their metabolites could be detected in heart blood,peripheral blood and major organs,and the contents of them changed dynamically with the preservation time.The contents of Aconitum alkaloids and their metabolites were higher in the spleen,liver and lung,especially in the spleen which was closer to the stomach.The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration.In contrast,the contents of Aconitum alkaloids and their metabolites in kidney were all lower.Aconi-tum alkaloids and their metabolites were not detected in urine.Conclusion Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits,diffusing from high-content organs(stomach)to other major organs and tissues as well as the heart blood.The main mechanism is the dispersion along the concentration gradient,while urine is not affected by postmortem diffusion,which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

Objective:To study the therapeutic effect of sacubitril valsartan combined metoprolol on patients with chronic cardiac insufficiency and its impact on levels of chemokine CXC ligand 13(CXCL13)and human cardiac sarcoplasmic reticulum calcium ion ATPase 2a(SERCA2a).Methods:This randomized controlled study enrolled 120 patients with chronic cardiac insufficiency admitted in Peking University Shenzhen Hospital between June 2018 and December 2021.They were divided into control group(n=60,metoprolol therapy)and combined treatment group(n=60,additional sacubitril valsartan therapy based on control group).After 90d treatment,therapeutic effect,cardiac function,coronary hemodynamics,levels of CXCL13 and SERCA2a,and safety were compared between two groups.Results:Total effective rate in combined treatment group was significantly higher than that of control group(91.67％vs.76.67％,P=0.024).Compared with patients in control group after treatment,those in combined treatment group had significant higher left ventricular ejection fraction(LVEF),cardiac output(CO),coronary diastolic peak veloci-ty(DPV),systolic peak velocity(SPV),diastolic velocity time integral(DVTI),systolic velocity time integral(SVTI)and SERCA2a level,and significant lower left ventricular end-diastolic volume(LVEDV),left ventricular end-diastolic di-ameter(LVEDd)and CXCL13 level(P＜0.001 all).We detected no significant difference in incidence of adverse reac-tions between two groups during treatment(P=0.378).Conclusion:Sacubitril valsartan combined with metoprolol has good therapeutic effect in patients with chronic cardiac insufficiency.It can improve cardiac function,increase the coronary blood flow velocity,reduce CXCL13 level and increase SERCA2a level with good safety.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

The purpose of this study was to investigate the effect of isorhyncophylline on hippocampal endogenous metabolites in spontaneously hypertensive rats (SHR) by ¹H NMR metabolomics and molecular docking. Twelve SHR were randomly divided into a model group and a treatment group. Six Wistar-Kyoto rats were selected as a control group. The rats in the treatment group were administered isorhyncophylline (0.3 mg·kg^-1) while the rats in the other two groups were treated with the same amount of sterilized saline solution. Animal experiment was authorized by the Ethics Committee of Shandong University of Traditional Chinese Medicine (No. SDUTCM20210721002). Hippocampal tissues were removed after administration for 8 weeks and assayed by ¹H NMR based metabolomics technology combined with a pattern recognition method to find characteristic metabolites, and the metabolic targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes database. Molecular docking technology was used to evaluate binding of isorhyncophylline to the core targets. The results of a principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed a clear cluster of samples among three groups. There were seven differentially altered metabolites, and glucose metabolism and glutamate metabolism were the principal related pathways. Molecular docking indicated that isorhyncophylline had good binding properties with nine key candidate target proteins. According to the above research results, isorhyncophylline can influence energy metabolism and glutamate metabolism in the hippocampus.

Objective:To study the effect of Biejiajian Wan on the epithelial-mesenchymal transition （EMT） of rat hepatic oval cells induced by transforming growth factor- β₁（TGF-β₁）， in order to explore its mechanism in reversing EMT. Method:WB-F344 cells were divided into five groups： blank group， TGF-β₁ model group （10 μg·L^-1TGF-β₁）， low-dose group （10 μg·L^-1TGF-β₁+0.55 g·kg^-1Biejiajian Wan）， medium-dose group （10 μg·L^-1TGF-β₁+1.1 g·kg^-1Biejiajian Wan）， high-dose group （10 μg·L^-1TGF-β₁+2.2 g·kg^-1Biejiajian Wan）. Except blank group， TGF-β₁ was used to induce WB-F344 cells in all of the remaining groups to construct an EMT model. After the cells were treated with low， medium and high doses of Biejiajian Wan serum， the changes of migration ability of WB-F344 cells were detected by cell scratching test. The expressions of E-cadherin， N-cadherin and Vimentin were detected by Western blot. Real-time PCR was used to detect the changes in the expression of β-catenin mRNA. The expression of β-catenin was detected by cell immunofluorescence assay. Result:Compared with normal WB-F344 cells， the intercellular space of WB-F344 cells became loose from tight， and the morphology changed from cobblestone to fibroblast after TGF-β₁ induced WB-F344 cells for 4 days， and the expression of E-cadherin protein decreased， while the expression of N-cadherin protein increased （P<0.01）， indicating that the EMT model of WB-F344 cells was successfully built. Compared with the blank group， the migration ability of WB-F344 cells in TGF-β₁ model group was enhanced （P<0.01）， compared with TGF-β₁ model group， Biejiajian Wan could significantly inhibit the migration ability of WB-F344 cells； specifically， the low-dose group had no statistical significance， and the medium and high-dose groups had statistical significance （P<0.05）. Western blot results showed that compared with the blank group， the expression of E-cadherin decreased， whereas those of N-cadherin and Vimentin increased in the TGF-β₁ model group （P<0.01）， compared with TGF-β₁ model group， E-cadherin protein expression was increased in the low， medium and high-dose groups， while the expressions of N-cadherin and Vimentin was decreased； specifically， the low-dose groups had no statistical significance， and the medium and high dose groups had statistical significance （P<0.05，P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expression of β-catenin in the TGF-β₁ model group was increased （P<0.05）， whereas compared with TGF-β₁ model group， the mRNA expression of β-catenin in the low， medium and high-dose groups of Biejiajian Wan was reduced （P<0.01）. The results of cellular immunofluorescence showed that compared with the blank group， the fluorescence expression of β-catenin in the cell nucleus was enhanced in the TGF-β₁ model group； and compared with the TGF-β₁ model group， the expression of β -catenin in the cell nucleus of the low， medium and high-dose groups of Biejiajian Wan decreased， and the inhibitory effect of Biejiajian Wan on β-catenin in the cell nucleus was positively correlated with its concentration. Conclusion:Biejiajian Wan may reverse the EMT process that TGF-β₁ induced WB-F344 cells， and inhibit the migration of WB-F344 cells by inhibiting Wnt/β-catenin signaling pathway.