Objective To identify the effective therapeutic targets of multiple system atrophy-parkinsonian type （MSA-P） based on clinical and electrophysiological assessment indices， and to investigate the clinical efficacy of low-frequency versus high-frequency repetitive transcranial magnetic stimulation （rTMS） applied to the primary motor cortex （M1 region） of the brain in patients with MSA-P. Methods A total of 40 patients with MSA-P who were diagnosed and treated in Jilin People’s Hospital from January 2023 to December 2024 were enrolled， and according to the frequency of rTMS， they were divided into low-frequency group with 20 patients and high-frequency group with 20 patients. The patients in the low-frequency group received 1 Hz rTMS over the M1 region， while those in the high-frequency group received 5 Hz rTMS over the M1 region， and clinical and electrophysiological assessments were performed for both groups at 1 week， 2 weeks， 4 weeks， and 3 months after intervention. Results After low-frequency or high-frequency rTMS was applied to the M1 region of MSA-P patients， there were no significant improvements in clinical and electrophysiological assessment indices in the low-frequency group， while the high-frequency group had significant improvements in clinical and electrophysiological assessment indices. Conclusion The primary motor cortex （M1 region） of the brain is an effective therapeutic target for MSA-P. Excitatory stimulation of the M1 region significantly improves the clinical and electrophysiological assessment indices of MSA-P， while inhibitory stimulation of the M1 region fails to achieve such improvements. This study shows that rTMS is an effective therapeutic modality for MSA-P and thus holds promise for clinical application. High-frequency rTMS over the M1 region can improve the symptoms of MSA-P and correct abnormal rhythmic activity within the cortex and related subcortical brain regions， thereby achieving a sustained therapeutic effect.

Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Atherosclerosis(AS)is a common cardiovascular disease,and its treatment and prevention have been the focus of medical research.AS an emerging technology,nanotechnology has unique advantages and plays an important role in the prevention,diagnosis and treatment of AS.This paper reviews the latest research on the application of nanotechnology in AS diseases,systematically discusses the role of nanotechnology in the diag-nosis and treatment of AS,and comprehensively analyzes the effects of nano-drug carriers based on different sur-face trimmers,loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment.The aim is to provide new thought for the clinical treatment of AS.

Objective:To explore the clinical value of antegrade transabdominal nasobiliary duct placement in the treatment of fine diameter choledocholithiasis in the elderly.Methods:From June 2021 to June 2022, 60 elderly patients with fine diameter common bile duct stones who were treatment in the Shandong Chengwu County People′s Hospital were enrolled. All patients underwent laparoscopic common bile duct exploration (LCBDE), 28 patients in the experimental group were underwent antegrade transabdominal placement of nasal bile ducts, 32 patients in the control group were treated with T-tube drainage. The operative index, postoperative complications and total medical expenses, postoperative patient satisfaction were compared between the two groups.Results:The operation was successful in both groups, and no conversion to laparotomy or death occurred. The indwelling time of common bile duct drainage, postoperative hospital stay in the experimental group were shorter than those in the control group, the incidence of postoperative pain was lower than that in the control group, the postoperative patient satisfaction was higher than that in the control group: (6.46 ± 1.04) d vs. (33.63 ± 1.19) d, (8.11 ± 0.74) d vs. (10.38 ± 1.54) d, 3.6%(1/28) vs. 21.9%(7/32), (9.21 ± 0.83) scores vs. (7.56 ± 0.62) scores, there were statistical differences ( P<0.05). The surgical time, postoperative activity time, gastrointestinal function recovery time and total medical expenses between the two groups had no statistical differences( P>0.05). The postoperative complications between the two groups had no statistical differences ( P>0.05). Conclusions:Anterior transabdominal nasobiliary duct placement can shorten the retention time and hospitalization time of the common bile duct drainage tube, reduce the incidence of postoperative complications, and promote rapid recovery. It is a safe and effective surgical method.

Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P＜0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)％,(0.82±0.03)％,(0.71±0.02)％,(0.62±0.03)％and(0.53±0.02)％vs(1.01±0.01)％,P＜0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P＜0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P＜0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P＜0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.

Objective To evaluate the potential of serum exosomal miR-148a-5p as a biomarker and to investigate its role in the pathogenesis of rheumatoid arthritis(RA).Methods A total of 80 participants(30 healthy controls,HCs;50 RA patients)were recruited.Serum exosomes were extracted and identified.The expressions of exsomal miR-148a-5p will be screened by next-generation sequencing,validated by qRT-PCR and assessed its clinical significance.Target genes and their functions were determined by the luciferase reporter assays,cell transfection,and ELISA.Results Fifty-five differentially expressed serum exomiRNAs were identified(44 upregulated,11 downregulated).The high expression of the exo-miR-148a-5p in the serum of patients with RA was validated by qRT-PCR,comparing to HCs(P<0.000 1),which showed a strong correlation with the disease activity score(DAS)28,rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)and exhibited higher sensitivity and specificity of diagnostic(AUC 0.8633,95%CI 0.77～0.95).CREB5 was the potential target gene of miR-148a-5p.CCK-8 assays showed that miR-148a-5p mimic significantly promoted proliferation of MH7A and M0 macrophages at 48 h and 72 h(P<0.005).The miR-148a-5p inhibitor inhibited proliferation of MH7A and M0 macrophage at 48 h slightly(P<0.05),and better effects shown at 72 h(P<0.001).Additionally,miR-148a-5p mimic significantly reduced CREB5 protein expression in MH7A cells and increased the levels of MMP3 and CXCL10 in culture supernatant(P<0.001),which could be reversed by miR-148a-5p inhibitor.However,miR-148a-5p had no impact on protein expression of RBMXL1 or CREB5 in M0 macrophages.Conclusion Serum exosomal miR-148a-5p is a diagnostic marker and involves in the pathogenesis of RA,which promotes MH7A cell proliferation by affecting protein levels of CREB5 and excessive secretion of MMP-3,CXCL10.

Objective To evaluate the potential of serum exosomal miR-148a-5p as a biomarker and to investigate its role in the pathogenesis of rheumatoid arthritis(RA).Methods A total of 80 participants(30 healthy controls,HCs;50 RA patients)were recruited.Serum exosomes were extracted and identified.The expressions of exsomal miR-148a-5p will be screened by next-generation sequencing,validated by qRT-PCR and assessed its clinical significance.Target genes and their functions were determined by the luciferase reporter assays,cell transfection,and ELISA.Results Fifty-five differentially expressed serum exomiRNAs were identified(44 upregulated,11 downregulated).The high expression of the exo-miR-148a-5p in the serum of patients with RA was validated by qRT-PCR,comparing to HCs(P<0.000 1),which showed a strong correlation with the disease activity score(DAS)28,rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)and exhibited higher sensitivity and specificity of diagnostic(AUC 0.8633,95%CI 0.77～0.95).CREB5 was the potential target gene of miR-148a-5p.CCK-8 assays showed that miR-148a-5p mimic significantly promoted proliferation of MH7A and M0 macrophages at 48 h and 72 h(P<0.005).The miR-148a-5p inhibitor inhibited proliferation of MH7A and M0 macrophage at 48 h slightly(P<0.05),and better effects shown at 72 h(P<0.001).Additionally,miR-148a-5p mimic significantly reduced CREB5 protein expression in MH7A cells and increased the levels of MMP3 and CXCL10 in culture supernatant(P<0.001),which could be reversed by miR-148a-5p inhibitor.However,miR-148a-5p had no impact on protein expression of RBMXL1 or CREB5 in M0 macrophages.Conclusion Serum exosomal miR-148a-5p is a diagnostic marker and involves in the pathogenesis of RA,which promotes MH7A cell proliferation by affecting protein levels of CREB5 and excessive secretion of MMP-3,CXCL10.

[This corrects the article DOI: 10.1016/j.apsb.2021.07.006.].

Objective:To investigate the clinical efficacy of three-dimensional (3D) laparos-copic radical resection of rectal cancer with left colic artery preservation and natural orfice specimen extraction surgery (NOSES).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 186 patients with rectal cancer who were admitted to Henan Provincial People's Hospital from December 2018 to December 2019 were colleted. There were 120 males and 66 females, aged from 30 to 81 years, with a median age of 59 years. Patients underwent 3D laparoscopic radical resection of rectal cancer. Observation indicators: (1) surgical and postoperative situations; (2) follow-up. Follow-up using outpatient examination or telephone interview was conducted to detect survival of patients and tumor recurrence up to January 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and percentages. Result:(1) Surgical situations: 186 patients with rectal cancer under-went 3D laparoscopic radical resection and postoperative with left colic artery preservation and NOSES. The operation time was (123±24)minutes, volume of intraoperative blood loss was (30±20)mL, the numer of lymph nodes dissected was 15±7. The time to postoperative first flatus, time to semiliquid food intake, time to postoperative out-of-bed activities were (2.3±0.7)days, (4.1±1.4)days, (2.9±1.0)days, respectively. The incidence of postoperative complications was 8.06%(15/186). The duration of postoperative hospital stay of 186 patients was (6.6±1.9)days and the treatment cost was (3.8±1.1) ten thousand yuan. Results of postoperative pathological examination showed 54 cases of low differentiated adenocarcinoma, 97 cases of moderate differentiated adenocarcinoma, 19 cases of high differentiated adenocarcinoma and 16 cases of mucinous adenocarcinoma. (2) Follow-up: 186 patients with rectal cancer were followed up for 13 to 24 months, with a median follow-up time of 13 months. During the follow-up, 18 patients had tumor recurrence or metastasis including 6 patients of death, 168 cases recovered well.Conclusion:3D laparoscopic radical resection of rectal cancer with left colic artery preservation and NOSES is safe and feasible.

Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2−/− and Ampkα2−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser485), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser485), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.