Prospective study on ultrasound-guided stellate ganglion block improves cerebral blood flow in patients with stroke.

OBJECTIVES: The effect of routine internal medicine and stroke rehabilitation treatment was not good. To confirm that ultrasound-guided stellate ganglion block (SGB) can improve cerebral blood flow in patients with stroke, Transcranial Doppler (TCD) and carotid ultrasound were used to monitor the cerebral blood flow parameters of ultrasound-guided SGB in patients with stroke. METHODS: A prospective study of 40 patients with stroke from January 2021 to October 2022 randomly divided into two groups (group SGB: undergoing ultrasound-guided SGB and standard medical procedures, control group: undergoing standard medical procedures) with 20 cases in each was conducted in People's Hospital of Chongqing Liang Jiang New Area. TCD and carotid artery ultrasound were monitored before and after treatment. There were no significant differences in general data on age, gender, disease course, and stroke type between two groups (P>0.05). RESULTS: After treatment, the bilateral ACA Vm of group SGB was significantly higher, the bilateral internal carotid artery RI and left VA RI were significantly lower than in control group (P<0.05). In group SGB, the Vm of bilateral MCA, bilateral PCA, right ACA, bilateral VA, and BA after treatment were significantly (P<0.05) increased compared to before treatment. PI of bilateral MCA, right ACA, and left VA after treatment were significantly (P<0.05) decreased compared to before treatment. RI of bilateral MCA, bilateral PCA, and bilateral VA after treatment were significantly (P<0.05) decreased compared to before treatment. Right internal carotid artery D after treatment was significantly (P<0.05) higher than before treatment. RI of bilateral internal carotid artery after treatment was significantly (P<0.05) lower than before treatment. CONCLUSIONS: Ultrasound-guided stellate ganglion block could improve local cerebral blood flow and vascular compliance in patients with stroke, and reduce vascular resistance.

Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.

Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.

SNX20 Expression Correlates with Immune Cell Infiltration and Can Predict Prognosis in Lung Adenocarcinoma.

BACKGROUND: Sorting nexin-20 (SNX20) is a member of the sorting nexin family of proteins. It plays a crucial role in the regulation of innate immunity. However, the prognostic risk, potential mechanisms, immunotherapy, and other functions of SNX20 in lung adenocarcinoma (LUAD) remain unclear. METHODS: We analyzed and validated the expression and prognostic role of SNX20 in LUAD through a combination of The Cancer Genome Atlas, Gene Expression Omnibus, Oncomine, TIMER, and Human Protein Atlas databases. Further, we analyzed the correlation between SNX20 expression and clinical characteristics of LUAD, and the prognostic value of SNX20 in LUAD was evaluated. Using fitted SNX20 expression and other clinical parameters, a predictive model with predictive performance for the overall survival of patients with LUAD was constructed. The potential biological function of SNX20 in LUAD was explored using gene set enrichment analysis. In addition, we analyzed the correlation between SNX20 expression and the immune microenvironment and survival. RESULTS: SNX20 was downregulated in most cancer types, was associated with poor prognosis in LUAD and could be an independent prognostic factor for patients with LUAD. The predictive model developed by us had good predictive power for determining the overall survival of patients with LUAD. Biofunctional analysis revealed that genes co-expressed with SNX20 mainly promoted the immune process and inhibited the cell proliferation process in LUAD. We observed that high expression of SNX20 was accompanied by a better immune microenvironment and survival in patients with LUAD. Furthermore, the LUAD immune response was elevated with an increase in SNX20 expression. Finally, we found that SNX20 expression was significantly associated with various tumor-infiltrating immune cells, and it was widely involved in regulating various immune molecules in LUAD and affecting immune infiltration in the tumor microenvironment. CONCLUSION: Our results suggested that SNX20 is a potential immune-related biomarker and therapeutic target associated with the prognosis of patients with LUAD. This provided a new strategy for the development of immunotherapeutic and prognostic markers in LUAD.

Effect of controlled low central venous pressure technique on postoperative hepatic insufficiency in patients undergoing a major hepatic resection.

OBJECTIVE: To investigate the effect of controlled low central venous pressure (CLCVP) technique on postoperative hepatic insufficiency in patients undergoing major hepatic resection. METHODS: In this single-center, propensity score matching, retrospective study, 331 patients who underwent laparoscopic major hepatectomy consecutively from October 1, 2014 to October 30, 2020 were enrolled and divided into a CLCVP group [0≤ central venous pressure (CVP) ≤5 cmH2O] and normal CVP (NCVP) group (5< CVP ≤10 cmH2O). The propensity score matching was used to adjust the differences in the data and was matched 1:1 to evaluate the impact of CLCVP on the incidence of liver insufficiency. RESULTS: After propensity score matching, 84 patients were included in each group, with a good balance of preoperative baseline and intraoperative data between the two groups. The incidence of postoperative hepatic insufficiency was 21.23% in the CLCVP group, which did not differ from that in the NCVP group (21.54%) (P>0.05). CONCLUSION: In patients undergoing laparoscopic major hepatectomy, CLCVP technique did not increase the incidence of postoperative hepatic insufficiency.

A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection

Influenza pandemic poses public health threats annually for lacking vaccine which provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens inducing cross-protective antibody response with epitopes activating cross-protective cytotoxic T-cells would offer an attractive strategy for developing universal vaccine. In this study, we constructed a recombinant protein NMHC consisting of influenza viral conserved epitopes and superantigen fragment. NMHC promoted the mature of bone marrow-derived dendritic cells and induced CD4+ T cells to differentiate into Th1, Th2 and Th17 subtypes. Mice vaccinated with NMHC produced high level of immunoglobulins which cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtypes) and group 2 (H3 subtype) influenza virus strains. And purified anti-NMHC antibodies could bind to multiple HAs with high affinities. NMHC vaccination effectively protected the mice from infection and lung damage challenged by two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T-cell responses to clear the virus from infected tissue and prevent virus spreading. In conclusion, this study provided proof of concept for triggering both B cells and T cells immune responses against multiple influenza virus infection, and NMHC may be a potential candidate of universal broad-spectrum vaccine for various influenza virus prevention and therapy.

Curcumin analog A13 alleviates oxidative stress by activating Nrf2/ARE pathway and ameliorates fibrosis in the myocardium of high-fat-diet and streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus is an important risk factor for cardiomyopathy. Increasing oxidative stress may be one of the main factors of diabetic cardiomyopathy. A13, a newly synthesized curcumin analog, was proved to be superior to curcumin in biological activity. However, little know about how A13 performed in diabetic models. In this study, we evaluated the ability of curcumin analog A13 to alleviate oxidative stress and ameliorate fibrosis in the myocardium, and explore the underlying mechanisms. METHODS: Intraperitoneal injection of streptozotocin (30 mg/kg in 0.1 M sodium citrate buffer, pH 4.5) induced diabetes in high-fat fed rats. The rats were respectively treated with a daily dose of curcumin or A13 via intragastric intubation for 8 weeks. Myocardial tissue sections were stained with hematoxylin-eosin; oxidative stress was detected by biochemical assays; activation of the Nrf2/ARE pathway was detected by Western blot, immunohistochemical staining and RT-qPCR; myocardial fibrosis was identified by Western blot and Masson trichrome staining. RESULTS: Treatment with curcumin analog A13 reduced the histological lesions of the myocardium in diabetic rats. Curcumin and A13 treatment decreased the malondialdehyde level and increased the activity of superoxide dismutase in the myocardium of diabetic rats. Molecular analysis and immunohistochemical staining demonstrated that dose of 20 mg/kg of A13 could activate the Nrf2/ARE pathway. Molecular analysis and Masson staining showed that curcumin analog A13 treatment significantly ameliorated fibrosis in myocardium of these diabetic rats. CONCLUSION: Treatment with curcumin analog A13 protects the morphology of myocardium, restores the MDA levels and SOD activity, activates the Nrf2/ARE pathway and ameliorates myocardial fibrosis in diabetic rats. It may be a useful therapeutic agent for some aspects of diabetic cardiomyopathy.

[Intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats].

OBJECTIVE: To investigate the intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats. METHODS: Sixty male SD rats, 10 rats were chosen as normal control group (NC), the other 50 rats were assigned to experiment group. Experiment diabetic rats were induced by high-fat food and intraperitoneal injection of steptozotocin (STZ). After the model was established successfully, diabetic rats were divided into four groups randomly: diabetes mellitus group (DM, n=12), curcumin treatment group (CUR, n=10), high dose treatment group of J7 (J+, n=10), low dose treatment group of J7 (J-, n=10). The CUR group were intragastrically administered with curcumin 20 mg/kg daily, in addition, the J+ group and the J- group were intragastrically administered with J7 20 mg/kg and 10 mg/kg daily respectively. After 8 weeks, the fast blood glucose was detected biochemically. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were detected by hydroxylamine method and thiobarbituric acid method respectively. The protein expressions of the nuclear factor-erythroid 2-related factor 2 (tNrf2), phosphorylation of Nrf2 (pNrf2), catalase (CAT), NAD(P)H quinine oxidoreductase 1 (NQO1) were measured by Western blot. The mRNA expressions of CAT, NQO1, hemeoxygenase-1 (HO1) were measured by quantitative real-time PCR (qRT-PCR). Morphological structure of testis was observed by hematoxylin-eosin (HE) staining. The expressions of Nrf2 and CAT were also detected by immunohistochemical method. RESULTS: The levels of fast blood glucose and MDA in DM group were increased significantly(P＜0.05), while the body weight, the activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of CAT, NQO1, HO1 were decreased (P＜0.05). Under light microscope, the DM group showed disrupted histological appearance. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were decreased. With the treatment of curcumin and J7, the MDA levels in the three treatment groups were decreased (P＜0.05). The activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of NQO1, HO1 were increased (P＜0.05). the levels of fast blood glucose were decreased in the J+ and J- group (P＜0.05), and the mRNA expression of CAT was increased in the J+ group (P＜0.05). The ratio of pNrf2/tNrf2 in the J+ group was significantly higher than that in CUR and J- group (P＜0.05). The protein level of CAT in the J+ group was also significantly higher than that in J- group (P＜0.05). There were no significant differences in other indexes among the three treatment groups. Under light microscope, the morphology was obviously improved in the three treatment groups. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were increased in the three treatment groups. It was suggested that high dose J7 had better antioxidant stress ability in testis of diabetic rats. CONCLUSION: Curcumin and J7 could inhibit the oxidative stress damage of testicular tissue in diabetic rats, which might be related with the activation of the Nrf2-ARE signaling pathway.

Ring-opened tetrahydro-γ-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms.

This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5-18) were synthesized and structure-activity relationship studies indicated that the change of the tetrahydro-γ-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials. In addition, attachment of different hydroxamic acid groups, the zinc binding motif at the N1 position, contributes to the antiproliferative activity in cancer cells. Several synthetic compounds exhibited potent growth inhibition in a broad spectrum of tumor cell lines, induced irreversible growth arrest capacities by suppressing colony formation ability and activated the apoptosis pathway. The data provide compelling evidence that our newly synthesized compounds with type B to D hydroxamic acid groups as the zinc binding motif at the N1 position are potent selective inhibitors of HDAC6 and could be investigated preclinically as potential anticancer drugs.

Combination of maintenance hemodialysis with hemoperfusion: a safe and effective model of artificial kidney.

OBJECTIVE: To investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve the quality of life of MHD patients and reduce their mortality rate. METHODS: This study was a prospective, randomized, controlled clinical trial. 100 MHD patients were selected and then randomly divided into two groups after four weeks of run-in period. Group 1 received HD alone 2 times a week and the combined treatment of HD with HP (HD+HP) once a week, whereas Group 2 was given HD alone 3 times a week. This study was followed up for a mean of 2 years. The primary outcome was the death of patients. Secondary end points included normal clinical data, leptin, high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), ß(2) microglobulin (ß(2)-MG), immunoreactive parathyroid hormone (iPTH), tumor necrosis factor-α (TNF-α) and the index of dimensions of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 Chinese Edition ). RESULTS: At the end of the two-year observation, the serum concentration of leptin, hsCRP, iPTH, IL-6, ß(2)-MG and TNF-α, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), cardiothoracic ratio, left ventricular mass index (LVMI), the EPO doses and the types of antihypertensive drugs used were lower with Group 1 than with Group 2 (p<0.05); Group 1 had higher hemoglobin (Hb), ejection fraction (EF), and body mass index (BMI) (p<0.05). No statistical difference between the two groups was observed in terms of serum albumin, serum iron (SI), total iron binding capacity (TIBC), cardiac output (CO), Kt/V, early/atrial mitral inflow velocities (E/A) (p>0.05). Besides, the SF-36 indicated that the total score of overall dimentions of Group 1 was higher than Group 2 (p<0.05) and the quality of life of Group 1 was evidently better than Group 2. The Kaplan-Meier Survival Curves for the 2-year observation period showed that patients in Group 1 had obvious survival advantage while Log-rank test results showed p<0.05. No serious adverse incidents occurred during the HD+HP treatment. CONCLUSIONS: HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body. These findings suggest a potential role for HD+HP in the treatment to improve the quality of life and survival rate of MHD patients.