Ulcerative colitis （UC） is a chronic intestinal autoimmune disease， with clinical manifestations including abdominal pain， diarrhea， mucus and bloody stools， and its pathogenesis is complex. The classic prescription Xianglian pills （XLP） has been widely used in the clinical treatment of UC in recent years. It has few adverse reactions， good patient tolerance， and shows significant potential for clinical application. However， there is currently no comprehensive integration of evidence on its clinical research and molecular mechanisms. Through a systematic review of the clinical research and molecular mechanisms of XLP in the treatment of UC， it is found that XLP and its modified formulas， when used in combination with chemical drugs， can significantly improve the symptoms of UC patients and reduce intestinal inflammation， with superior efficacy compared to chemical drugs alone. Its mechanism of action involves regulating pan-apoptosis， immune response， signaling pathways （hypoxia-inducible factor-1α， nuclear factor-κB， etc.）， intestinal flora， and repairing the intestinal mucosal barrier. Its medicinal materials， monomers and active components can also prevent the differentiation of helper T cells 17 and restore the balance of M1/M2 cells through regulating multiple pathways such as Wnt/β -catenin and Janus kinase/signal transducer and activator of transcription， thereby reducing intestinal damage in UC.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Objective:To investigate the application value of Th1/Th2 cytokines,interleukin-17(IL-17)and serum tumor markers in the diagnosis,prognosis and recurrence of breast cancer.Methods:A total of 200 patients with breast cancer admitted to Inner Mongolia Hospital of Peking University Cancer Hospital from December 2021 to December 2022 were selected,and they were divided into negative group(60 cases),weakly positive(80 cases)group and positive group(60 cases)according to immunohistochemistry indicators.In addition,another 60 persons who underwent physical examination were selected as healthy control group.The changes of the Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA levels were observed,and the clinical value of the combined detection of the 6 indicators in predicting the prognosis and recurrence of breast cancer was investigated.Results:The results of comparative analysis indicated that the clinical pathological features related to recurrence,histological grading,tumor diameter and lymph node metastasis(x2=7.552,12.037,12.063,8.543,P＜0.05),respectively.Multivariate analysis showed that tumor recurrence,tissue grading,tumor diameter and lymph node metastasis were the important factors for the prognosis of patients with breast cancer(OR=3.096,3.050,3.425,3.031,P＜0.05).Compared with the single prediction of Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA,the combined prediction of 6 indicators had higher clinical value for prognosis and recurrence of patients with breast cancer,which sensitivity,accuracy and specificity were respectively 96%,93.46%and 85%.Conclusion:The observation on the changes of the combined predictive levels of 6 items,which include Th1/Th2,IL-17,CA125,CYFRA21-1,CA153 and CEA of patients,indicates that the combined detection has high sensitivity and accuracy.This highly efficient and convenient detection method can provide references for improving the prognosis,reducing the recurrence and enhancing the accuracy of assessment.

Objective:To observe any effects of repetitive high-frequency transcranial magnetic stimulation (rTMS) on the upper limb motor function of stroke survivors with right hemiplegia.Methods:Forty stroke survivors with right hemiplegia were divided at random into a high-frequency rTMS group and a sham stimulation group, each of 20. In addition to routine rehabilitation, the high-frequency rTMS group was given daily high-frequency rTMS 5d per week for 2 weeks, while the sham stimulation group was provided with sham rTMS. Before and after the treatment, both groups were evaluated using the Fugl-Meyer Upper Extremity motor function evaluation scale (FMA-UE), surface electromyography (sEMG), and electroencephalographic microstatus testing. Any adverse reactions in the course of the treatment were recorded.Results:After the treatment, the average FMA-UE scores of both groups had improved significantly, with the average of the high-frequency rTMS group significantly higher than the other group′s average. After the treatment the peak-to-peak sEMG value of the radial long extensor carpi radialis longus muscle in the high-frequency rTMS group was significantly higher than before the treatment and significantly higher than that of the other group. The temporal coverage of microstate B, the average duration and temporal coverage of microstate C, and the temporal coverage and frequency of occurrence of microstate D after treatment of both groups were also significantly improved. The mean duration of electroencephalographic (EEG) microstate A was negatively correlated with the FMA-UE scale scores ( r=-0.57) and its temporal coverage was positively correlated with the peak-to-peak sEMG value of the ulnar lateral wrist flexor. The mean duration of EEG microstate B was positively correlated with the peak-to-peak sEMG value of the triceps brachii and deltoid, and the mean duration of EEG microstate C was also positively correlated with the peak-to-peak sEMG value of the deltoid muscle. Conclusions:High-frequency rTMS can effectively improve the upper limb motor functioning of stroke survivors with right hemiparesis. After high-frequency rTMS, the functional network activity related to EEG microstate B increases significantly, while that related to microstates C and D decreases significantly.

ObjectiveTo explore the brain mechanism of repetitive transcranial magnetic stimulation (rTMS) on dysfunction after stroke using functional magnetic resonance imaging (fMRI). MethodsLiteratures about the functional magnetic resonance imaging study about repetitive transcranial magnetic stimulation for dysfunction after stroke were retrieved in PubMed, Web of Science, CNKI and Wanfang data from establishment to June 1st, 2021. The quality of the literature was evaluated with Physiotherapy Evidence Database (PEDro) scale. Literature screening, and data extraction were performed by two researchers. ResultsA total of 14 randomized controlled trials were finally enrolled. They were of high or very high quality. They mainly involved the therapeutic effect and imaging mechanisms of rTMS on dysfunction after stroke. ConclusionrTMS could change the excitability of the cerebral cortex and the effective connections between brain regions after stroke, promote the reorganization of brain function, and achieve the recovery of post-stroke dysfunction.

In recent years, studies have shown that transplanted neural stem cells (NSCs) help neural tissues regenerate and return to normal through paracrine action rather than just replacing cells. Exosomes are essential paracrine mediators that can participate in cell communication through substance transmission. This review focuses on NSCs regulated by exosomes and their application in treatment of nervous system diseases, in order to provide important references for further research and clinical application of NSCs exosomes..

Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.

Objective:To compare the perioperative complications and prognosis of intracorporeal and extracorporea lileal conduit urinary diversion(ICUD or ECUD)following robot-assisted radical cystectomy(RARC).Methods:The data of 95 patients who underwent RARC treatment in Nanjing Drum Tower Hospital from March 2016 to June 2019 were retrospectively analyzed. Among them, 37 underwent ICUD and 58 underwent ECUD. In the ICUD group, there were 32 males and 5 females, aged(68.0±7.8) years, body mass index (BMI) of (24.1±3.4) kg/m 2, American Society of Anesthesiologists(ASA)score of 1-2 in 4 cases(10.8%), ASA score of 3-5 in 33 cases(89.2%), preoperative hemoglobin of(126.5±14.2)g/L, albumin of(39.0±2.2)g/L, and C-reactive protein of 4.0(2.0-8.5) mg/L. In the ECUD group, there were 53 males and 5 females, aged(67.5±9.0)years, BMI of(24.2±3.6)kg/m 2, ASA score of 1-2 in 16 cases(27.6%), ASA score of 3-5 in 42 cases (72.4%) , preoperative hemoglobin of(129.0±12.4)g/L, albumin (38.2±3.1) g/L, and C-reactive protein of 4.9 (3.1-14.4) mg/L. There was no significant difference in preoperative data between the two groups ( P>0.05). The two groups underwent RARC and pelvic lymph node dissection similarly. The ICUD group underwent a total intracorporeal ileal conduit and the ECUD group underwent extracorporeal ileal conduit with direct vision through a median incision in the lower abdomen.There were 32 cases (86.5%) and 46 cases (79.3%) undergoing expanded pelvic lymph node dissection in the ICUD group and the ECUD group respectively, and the difference was not statistically significant ( P=0.374). The complications were graded according to the Clavien-Dindo grading system. The perioperative complications and prognosis of the two groups were compared. Results:The operation time of the ICUD group and the ECUD group were (430±63) min vs. (410±69) min, respectively ( P=0.163). The estimated blood loss were (435±233) ml vs. (388±277) ml, respectively ( P=0.182). Intraoperative blood transfusion were 10 cases (27.0%) and 12 cases (20.7%)( P=0.475). None of the above differences were statistically significant. Postoperative albumin of the ICUD group and the ECUD group were (31.5±2.4) g/L vs. (31.0±2.8) g/L ( P=0.387), postoperative C-reactive protein were 30.9 (10.4-52.1) mg/L vs.29.5 (14.4-58.5) mg/L ( P=0.655) and postoperative hemoglobin were (110.0±13.8) g/L vs. (113.7±13.4) g/L ( P=0.187). The postoperative feeding recovery were 4(3-5) d vs. 4(3-5) d ( P=0.752) and the postoperative hospital stay were 13(10-19) d vs. 13(11-18) d ( P=1.000). There was no statistically significant difference in perioperative data. The postoperative pathological examination results of ICUD group and ECUD group showed that there were 17 cases (45.9%) vs.19 cases (32.8%) in T a/T 1/Tis stage, 12 cases (32.4%) vs. 18 cases (31.0%) in T 2 stage, 5 cases (13.5%) vs. 19 cases (32.8%) in T 3 stage, 3 cases (8.1%) vs. 2 cases (3.4%) in T 4 stage, respectively and the difference was not statistically significant( P=0.166). The number of lymph nodes removed were (18.2±6.7) vs.(16.5±7.9)( P=0.178) and the number of patients with positive lymph nodes were 6(16.2%) vs.11(19.0%), respectively( P=0.733). None of the patients had positive margins. There was no statistically significant difference in pathological examination overall. There were 14 cases (37.8%) in the ICUD group and 21 cases (36.2%) in the ECUD group experiencing complications within 30 days after operation and the difference was not statistically significant( P=0.872). The complications within 90 days after operation were 14 cases (37.8%) vs. 24 cases (41.4%) respectively and the difference was not statistically significant( P=0.731). Clavien-Dindo grade Ⅲ-Ⅴ complications in the two groups were 1 case (2.7%) vs.1 case (1.7%) respectively, with no significant difference ( P=0.849). One patient in the ICUD group developed an intestinal anastomotic leakage and underwent reoperation for repairing and 1 patient in the ECUD group developed mechanical intestinal obstruction and underwent reoperation. The rate of readmission within 90 days after operation of the ICUD group was lower than that of the ECUD group, but the difference was not statistically significant [3 cases (8.1%) vs. 11 cases (19.0%), P=0.090]. Postoperative follow-up was 13-53 months and the median follow-up of ICUD group and ECUD group were 19 months and 31 months respectively. There was no significant difference in the survival curve between the two groups( P=0.746). The 1-year survival rate was 91.9% in the ICUD group and 91.4% in the ECUD group. Routine re-examination of urinary system CT or B-ultrasound was performed 3 months, 6 months and 1 year after surgery. The incidence of ureteral dilatation/hydronephrosis in the ICUD group was lower than that of the ECUD group, with 4.1%(3 sides) vs. 14.7%(17 sides)( P=0.020). Conclusion:Compared with RARC+ ECUD, RARC+ ICUD does not increase the incidence of complications within 90 days after surgery and may reduce the risk of upper urinary tract dilatation.

OBJECTIVE: To investigate the effect of low-frequency pulsed electromagnetic fields (PEMF) on the maturation and mineralization of rat cranial osteoblasts and its relation to IGF-1R/NO signaling pathway. METHODS: The rat osteoblasts were isolated and cultured and randomly divided into blank control group, PEMF group, GSK group (IGF-1R blocker) and PEMF+GSK group. The cells were treated with 50 Hz 0.6 mT PEMF for 1.5 h/d. After 3 d of PEMF treatment, the expressions of protein kinase (AKT), inducible nitric oxide synthase (iNOS) and cGMP-dependent protein kinase (PKG) were detected by Western blotting; on 6 d of PEMF treatment alkaline phosphatase (ALP) activity was determined; on 12 d of PEMF treatment the calcification nodule formation was demonstrated by Alizarin red staining. RESULTS: NO level was significantly increased in rat osteoblasts treated with 50 Hz 0.6 mT PEMF for 1.5 h/d. Western blot analysis showed that the expressions of AKT, iNOS and PKG protein in PEMF group were higher than those in the control group (all <0.01); the ALP activity was increased(<0.05), and the PEMF group had the largest area of Alizarin red staining (<0.01). The expressions of AKT, iNOS and PKG protein in GSK group were lower than those in the control group; the ALP activity was decreased (<0.05), and the GSK group had the least area of Alizarin red staining (<0.01). The expressions of AKT, iNOS, PKG protein, the ALP activity and the area of Alizarin red staining in PEMF+GSK group were between PEMF group and GSK group. CONCLUSIONS PEMF may enhance the maturation and mineralization of rat cranial osteoblasts through IGF-1R/NO signaling pathway.
Animals ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Electromagnetic Fields ; Nitric Oxide ; metabolism ; Osteoblasts ; radiation effects ; Rats ; Receptor, IGF Type 1 ; metabolism ; Signal Transduction ; radiation effects