ObjectiveTo investigate the effect of total glucosides of paeony （TGP） on neurotoxicity induced by aqueous extract of Strychni Semen （SA） in mice and to explore its mechanism. MethodThirty-two male KM mice were randomly divided into normal group，SA group （19.5 mg·kg^-1），TGP group （225 mg·kg^-1），and SA+TGP group （SA 19.5 mg·kg^-1+TGP 225 mg·kg^-1）. The open field test and beam walking test were used to observe the behavioral changes in mice. Pathological changes in the Nissl bodies of the cerebral cortex were assessed through Nissl staining. The levels of malondialdehyde （MDA），glutamate （Glu） in the mouse brain tissue，and serum levels of 5-hydroxytryptamine （5-HT） were detected using enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was employed to analyze gene expression profiles in the brain tissue. Common differentially expressed genes （DEGs） underwent gene ontology （GO） and kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses. The mRNA expression levels of key targets were determined using quantitative real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group，the SA group exhibited significant increases in side-to-side distance and average speed in the open field test，as well as increased walking time on the balance beam. The axons of cortical neurons were absent，and the levels of Glu and MDA in the brain tissue were significantly elevated （P<0.05，P<0.01），along with a notable increase in serum 5-HT levels （P<0.05）. In contrast to the SA group，the SA+TGP group significantly reduced the side-to-side distance，average speed，and balance beam walking time （P<0.05 or P<0.01）. The neuronal axons were clearly visible，and levels of 5-HT，Glu，and MDA were decreased （P<0.05，P<0.01）. Transcriptome analysis indicated that TGP could regulate the glutamate receptor，ionotropic，N-methyl-D-aspartate 2a （GRIN2A）/phospholipase C β₁ （PLCB1）/protein kinase C，gamma （PRKCG） signaling pathway. Compared with the normal group，SA significantly decreased the expression of GRIN2A，PLCB1，and PRKCG genes in the mouse brain （P<0.01），while the mRNA levels of GRIN2A and PRKCG significantly increased after TGP administration （P<0.05，P<0.01）. ConclusionSA induces significant neurotoxicity in the mouse brain，and TGP significantly alleviates SA-induced neurological damage，potentially through the GRIN2A/PLCB1/PRKCG signaling pathway.

Objective To observe the efficacy of percutaneous mechanical thrombectomy(PMT)for treating different traditional Chinese medicine(TCM)syndrome type lower extremity arterial thromboses.Methods Forty patients with lower extremity arterial thromboses who underwent PMT were retrospectively enrolled and divided into dampness-heat syndrome group(n=18)and blood stasis syndrome group(n=22)according to TCM syndrome types.The technical success rate,ankle-brachial index(ABI),Rutherford grade and vascular patency rate 12 months after PMT were compared between groups.Perioperative complications and adverse events during follow-up were recorded.Results The technical success rate of PMT in dampness-heat syndrome group and blood stasis syndrome group was 94.44%(17/18)and 100%(22/22),respectively.Twelve months after PMT,ABI was 0.45±0.11 and 0.52±0.14,and vascular patency rate was 94.44%(17/18)and 81.82%(18/22)in dampness-heat syndrome group and blood stasis syndrome group,respectively,both not significantly different between groups(all P＞0.05).No significant difference of Rutherford grade before treatment was found between groups(P＞0.05),while 12 months after PMT,Rutherford grade in dampness-heat syndrome group was higher than in blood stasis syndrome group(P＜0.05).During perioperative period,false aneurysm of brachial artery occurred in 1 case in dampness-heat syndrome group,while osteofascial compartment syndrome and atrial fibrillation occurred each in 1 case in blood stasis syndrome group,both relieved after treatments.No serious adverse event such as amputation nor death occurred during follow-up.Conclusion PMT was effective and safe for treating different TCM syndrome type lower extremity arterial thromboses.The prognosis of patients with blood stasis syndrome type lower extremity arterial thromboses was better than that of those with dampness-heat syndrome.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Abdomen/diagnostic imaging* ; Artificial Intelligence ; Body Composition ; Magnetic Resonance Imaging ; Practice Guidelines as Topic

ObjectiveBased on the antidepressant activity， the optimal ratio of Rehmanniae Radix and Lilii Bulbus in Baihe Dihuangtang was optimized and its possible mechanism was preliminarily explored. MethodA total of 100 male mice were randomly divided into normal group， model group， Rehmanniae Radix single decoction group， Lilii Bulbus single decoction group， and 5 different ratios of Baihe Dihuangtang group （Rehmanniae Radix-Lilii Bulbus 5∶6， 5∶5 ， 5∶4， 5∶3， 5∶2）， fluoxetine hydrochloride group. Except for the normal group， the remaining 9 groups were treated with chronic unpredictable mild stress method （CUMS） for 21 consecutive days to establish the depression mouse model.The Rehmanniae Radix single decoction group， Lilii Bulbus single decoction group and 5 different ratios of Baihe Dihuangtang group were administered with corresponding drugs at a dose of 2 g·kg^-1 respectively， and fluoxetine hydrochloride group was administered fluoxetine hydrochloride at a dose of 0.01 g·kg^-1， the normal group and the model group were respectively given an equal volume of normal saline by gavage for 21 consecutive days. The antidepressant effect of Baihe Dihuangtang with different ratios was evaluated by behavioral experiments. Western blot was used to detect the expression levels of brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB） in hippocampus. The level of total superoxide dismutase （SOD） in hippocampus was detected by hydroxylamine method. The level of reduced glutathione （GSH） in hippocampus was detected by spectrophotometric method. The levels of glutathione peroxidase （GPX） and glutathione S-transferase （GST） in hippocampus was detected by colorimetric method. The level of malondialdehyde （MDA） in hippocampus was detected by thiobarbituric acid method， and preliminary exploration of its antidepressant mechanism. ResultCUMS caused a significant decrease in the preference rate of sugar water and a significant prolongation of forced swimming and tail suspension immobility time （P<0.01）， while the different ratios of Baihe Dihuangtang and the single decoction of Rehmanniae Radix and Lilii Bulbus were significantly reversed to varying degrees. Abnormalities of the above indicators were observed （P<0.05， P<0.01）， especially when the ratio of 5∶6 had the most obvious effect on the above indicators， Moreover， CUMS caused the hippocampal BDNF and the expression of TrkB， SOD and glutathione antioxidant-related indexes were significantly decreased （P<0.01）， and the levels of lipid peroxidation product MDA was significantly increased （P<0.01）. However， the superior ratio of Baihe Dihuangtang （Rehmanniae Radix-Lilii Bulbus 5∶6， 5∶5， 5∶4） and the single decoction of Rehmanniae Radix and Lilii Bulbus significantly reversed the abnormality of the above indicators to varying degrees （P<0.05， P<0.01）. ConclusionIn summary， 5 different ratios of Baihe Dihuangtang and the single decoction of Rehmanniae Radix and Lilii Bulbus can produce antidepressant effect， especially when the ratio of 5∶6 had the most obvious effect on the above indicators， and the antidepressant effect gradually weakens with the proportion of Lilii Bulbus in the recipe decreases， and its mechanism may involve enhancing the nutritional level and antioxidant defense ability of hippocampal central nervous system.

Objective:To evaluate the characteristics of adult abdominal fat distribution and analyze its influencing factors by energy spectrum CT scan.Methods:The body height, weight, waist circumference, and hip circumference of 105 adults were measured, and the characteristics of abdominal fat distribution were evaluated by energy spectrum CT scan.Results:Compared with non-obese individuals, the contents of abdominal subcutaneous fat, abdominal cavity and liver ectopic fat were higher in obese patients ( P<0.05), and the intramuscular fat (IMAT) content did not increase with the increase of BMI. In middle-aged group, the waist circumference, waist-to-hip ratio (WHR) abdominal cavity area and IMAT content were higher than those in the youth group, and the muscle content of the middle-aged group was lower than that of the youth group, the difference between the two groups was significant ( P<0.05); the male group had higher abdominal cavity area and muscle content than the female group, while the female group had higher the subcutaneous fat area, abdominal subcutaneous fat thickness and erector spinae fat content than the male group, the differences were significant ( P<0.05). Conclusions:The characteristics of abdominal fat distribution of subjects with different BMI, age and gender were different. Therefore, we should pay attention to the individual assessment of ectopic fat distribution in obese patients. Energy spectrum CT can be used as an important approach for the assessment of ectopic fat to provide evidence for developing individualized weight loss programs.

Objective:Shizukuishi scoring method was used to compare the diagnostic value of parotid gland and submandibular gland scintigraphy for Sj?gren's syndrome (SS).Methods:Parotid gland and submandibular gland scintigraphy were conducted in 124 SS patients and 91 control subjects respectively, the results of scintigraphy of each gland were evaluated by excretion rate and 0-3 points per gland, the diagnostic accuracy of parotid and submandibular gland scintigraphy was compared by receiver operating characteristic curve (ROC).Results:The score of parotid scintigraphy was 0-6, with the cut-off value of 2, the sensitivity for diagnosis of SS was 76.9%, the specificity was 72.6%, the area under the curve (AUC) was (0.798±0.030). The score of submandibular scintigraphy was 0-6, with the cut-off value of 2. The sensitivity for diagnosis of SS was 78.0%, the specificity was 78.2%, the area of AUC was 0.854±0.026.Conclusion:The diagno-stic value of the submandibular gland scintigraphy is good.

PURPOSE: C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that is overexpressed in many cancers. CtBP1 transcriptionally represses a broad array of tumor suppressors, which promotes cancer cell proliferation, migration, invasion, and resistance to apoptosis. Recent studies have demonstrated that CtBP1 is a potential target for cancer therapy. This study was designed to screen for compounds that potentially target CtBP1. METHODS: Using a structure-based virtual screening for CtBP1 inhibitors, we found protocatechuic aldehyde (PA), a natural compound found in the root of a traditional Chinese herb, Salvia miltiorrhiza, that directly binds to CtBP1. Microscale thermophoresis assay was performed to determine whether PA and CtBP1 directly bind to each other. Further, clustered regularly interspaced short palindromic repeats associated Cas9 nuclease-mediated CtBP1 knockout in breast cancer cells was used to validate the CtBP1 targeting specificity of PA. RESULTS: Functional studies showed that PA repressed the proliferation and migration of breast cancer cells. Furthermore, PA elevated the expression of the downstream targets of CtBP1, p21 and E-cadherin, and decreased CtBP1 binding affinity for the promoter regions of p21 and E-cadherin in breast cancer cells. However, PA did not affect the expression of p21 and E-cadherin in the CtBP1 knockout breast cancer cells. In addition, the CtBP1 knockout breast cancer cells showed resistance to PA-induced repression of proliferation and migration. CONCLUSION Our findings demonstrated that PA directly bound to CtBP1 and inhibited the growth and migration of breast cancer cells through CtBP1 inhibition. Structural modifications of PA are further required to enhance its binding affinity and selectivity for CtBP1.

Objective To investigate the clinical efficiency,safety and prognostic factors of secondline chemotherapy regimen with gemcitabine combined with rituximab in the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma.Methods A total of 157 patients with relapsed or refractory B-cell nonHodgkin lymphoma were selected from July 2008 to February 2015 in Xi'an Central Hospital.Among them,87 patients were given GEMOX regimen (gemcitabine + oxaliplatin) combined with rituximab,and 70 patients were given GDP program (gemcitabine + cisplatin + dexamethasone) combined with rituximab.The chemotherapy efficacies of the two groups were evaluated.At the same time,the patients were grouped according to whether rituximab was applied or not,and the total objective response rate (ORR) difference was compared.The relevant prognostic factors affecting overall survival (OS) were found.The adverse reactions of patients after treatment were observed.Results The ORR of the GEMOX regimen combined with rituximab group was 65.5％,and the ORR of the GDP regimen combined with rituximab group was 55.7％,but the difference between the two groups was not statistically significant (x2 =1.58,P =0.210).The ORR was 75.2％ in 105 patients who had not used rituximab,and the ORR was 32.7％ in 52 patients who had previously received rituximab.The difference between the two groups was statistically significant (x2 =29.50,P ＜ 0.001).Univariate analysis showed that middle-high risk or high risk of the lymphoma international prognostic index (IPI) score (x2 =69.21,P ＜0.001),lactate dehydrogenase (LDH) increased (x2 =16.90,P ＜0.001),refractory patients (x2 =14.43,P =0.001),large mass (x2 =4.57,P =0.030),and failure to achieve CR or PR after salvage chemotherapy (x2 =50.85,P ＜ 0.001) were risk factors for OS.Cox multivariate analysis showed that middle-high risk or high risk of IPI (HR =2.138,95％ CI:1.301-3.512,P =0.001),refractory patients (HR =3.157,95％CI:1.001-10.644,P =0.014),failure to achieve CR or PR after salvage chemotherapy (HR=3.017,95％CI:2.218-7.366,P＜0.001),LDH increased (HR =2.236,95％ CI:1.797-2.781,P =0.001),large mass (HR =1.792,95％ CI:1.255-2.558,P ＜ 0.001) were independent risk factors affecting OS.Adverse reactions to chemotherapy were neutropenia,thrombocytopenia,nausea and vomiting,liver damage and cardiotoxicity,with no treatment-related death.Conclusion The second-line chemotherapy regimen containing gemcitabine combined with rituximab has a better curative effect on relapsed or refractory B-cell non-Hodgkin lymphoma,and the safety is good.Middle-high risk or high risk of IPI,refractory patients,failure to achieve CR or PR after salvage chemotherapy,elevated LDH and large mass were independent risk factors for OS.In patients with relapsed or refractory disease after rituximab treatment,re-application of rituximab was not effective.