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Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.
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Objective To explore the effect of Shuanglu Tongnao Formula on neuronal ferroptosis in ischemic stroke rats and its regulatory mechanism on the silent information regulator 2 homolog 1(SIRT1)/nuclear factor erythroid 2-related fac-tor 2(Nrf2)/glutathione peroxidase 4(GPx4)signaling pathways.Methods Twenty rats were selected as sham operation group by the random number table method,and the remaining seventy rats were made ischemic stroke rat models by the middle cerebral artery occlusion method.The rats that had been successfully modeled were randomly divided into the model control group,Shuanglu Tongnao formula group,Shuanglu Tongnao formula+SIRT1 inhibitor group(Shuanglu Tongnao formula+EX527 group),with 20 rats in each group.After 14 days,the rats were scored for neurological injury;TTC staining was applied to detect the area of cerebral infarction in rats;HE staining was applied to detect pathological changes in rat brain tissue;Nissl staining was applied to detect the number of neurons in rat brain tissue;the kit was applied to detect the levels of ferri ion(Fe2+),superoxide dismutase(SOD),glutathione(GSH),and malonaldehyde(MDA)in rat brain tissue;immunohistochemistry was applied to de-tect the positive expression of acyl-CoA synthetase long-chain family member 4(ACSL4),transferrin receptor(TFR),and ferritin heavy polypeptide 1(FTH1)proteins in rat brain tissue;Western blotting method was applied to detect the expression of SIRT1,Nrf2,GPx4,and cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11)proteins in rat brain tissue.Results Compared with the sham operation group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expressions of ACSL4 and TFR in model control group were increased(P<0.05);the number of neurons,the con-tents of SOD and GSH,the protein expression of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 were all reduced(P<0.05).Compared with the model control group,the neurological deficit score,cerebral infarction area,the contents of Fe2+and MDA,and the protein expression of ACSL4 and TFR in the Shuanglu Tongnao formula group were reduced(P<0.05),and the number of neurons,the contents of SOD and GSH,the protein expressions of FTH1,SIRT1,Nrf2,GPx4,and SLC7A11 are all increased(P<0.05).The results of the SIRT1 inhibitor supplementation experiment showed that the SIRT1 inhibitor reversed the inhibitory effect of Shuan-glu Tongnao formula on neuronal ferroptosis,while also inhibited the expression of Nrf2 and GPx4(P<0.05).Conclusion The Shuanglu Tongnao formula may inhibit neuronal ferroptosis in ischemic stroke rats by activating the SIRT1/Nrf2/GPx4 signa-ling pathway.
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Objective To investigate the correlation between Yes-associated protein(YAP)nuclear expression and tumor size with prognosis of patients with epithelial ovarian cancer(EOC)and to study the role of YAP in EOC.Methods 120 patients with EOC were selected as the experimental group,including 38 patients with early stage(Ⅰ+Ⅱ)EOC and 8 2 patients with advanced stage(Ⅲ+Ⅳ)EOC.3 0 normal ovarian tissues obtained from patients with uterine leiomyoma were enrolled as the control group.Immunohistochemical(IHC)assay was em-ployed to determine YAP expression and sub-location.The relationship between YAP expression and the pathologi-cal parameters of the 120 patients with EOC was analyzed,so as to the prognosis of these patients.EOC cells(C13K and OV2008)were cultured with varying initial cell volumes.Ki67 expression and cell proliferation were tested by immunofluorescence and cloning assay respectively.YAP expression at mRNA and protein levels were de-tected by q-PCR and Western blot respectively when the cell conference of EOC cells reached to low(60％)and high(90％)cell density.Results The YAP nuclear expression was significantly higher in the EOC group com-pared to the control group(P＜0.05).The average diameter of stage Ⅰ+Ⅱ EOC was larger than that of stage Ⅲ+Ⅳ EOC(P＜0.01).The high nuclear expression of YAP was positively associated with pathological grade,clinical stage and the level of Ca125＞1 000 IU/ml,while negatively correlated with tumor size(all P＜0.05).Survival analyses showed that smaller tumor size(＜10 cm)and higher YAP nuclear expression were negatively as-sociated with the 3-year overall survival rate of EOC patients(P＜0.01).C13K and OV2008 cells cultured in the low density group exhibited a high number of clone formation,high Ki67 and YAP expression(P＜0.01).The down-regulation of YAP expression could decrease the cell viability of EOC cells in the low-and high-density groups(P＜0.05).Conclusion Higher level of YAP nuclear expression and smaller tumour size are inversely associated with the clinical prognosis of patients with EOC.Inhibiting YAP nuclear expression leads to a decrease in the prolif-eration capacity of EOC cells.
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Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.
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Objective To investigate the plasma levels of methylated DNA in the pregnant women with preeclampsia and its predictive value for the occurrence of preeclampsia.Methods A total of 82 pregnant women with preeclampsia admitted to the hospital from January to December 2022 were included as the obser-vation group,and another 82 healthy pregnant women were included as the control group.Total DNA was ex-tracted,and the relative expression levels of methylated single-intention homolog 2(SIM2),guanine nucleo-tide-binding protein(GNA12),and connective tissue growth factor(CTGF)genes in plasma were detected by real-time fluorescence quantitative PCR(qRT-PCR)after DNA bisulfite modification.The value of methyla-ted DNA in predicting preeclampsia was evaluated by correlation analysis and receiver operating characteristic(ROC)curve.Results The relative expression levels of methylated SIM2,GNA12 and CTGF in plasma in the observation group were significantly higher than those in the control group(P＜0.05),and the relative expres-sion levels of methylated SIM2,GNA12 and CTGF in severe preeclampsia group was higher(P＜0.05).Corre-lation analysis showed that the relative expression levels of methylated SIM2,GNA12 and CTGF in plasma were significantly positively correlated with the occurrence of preeclampsia in pregnant women(P＜0.05).ROC curve analysis results showed that the relative expression levels of plasma methylation SIM2,GNA12,and CTGF,both individually and in combination,had good predictive efficacy in predicting preeclampsia in pregnant women,and the combined detection of the three had the highest predictive efficacy(area under the curve was 0.888,95％CI:0.827-0.949).Conclusion Compared with healthy pregnant women,the relative expression levels of methylated SIM2,GNA12 and CTGF in plasma are higher in pregnant women with pre-eclampsia,which are positively correlated with the occurrence of preeclampsia and the severity of the disease.The relative expression levels of methylated SIM2,GNA12 and CTGF are expected to be important predicting indicators for preeclampsia.
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Objective To study the effect of microRNA-192(miR-192)on the proliferation,migration and invasion ability of colorectal cancer(CC)cell lines.Methods Group A(SW1116 CC transfected with physio-logical saline),group B(SW1116 CC transfected with miR-192 mimics)and group C(SW1116 CC transfected with miR-192 inhibitor)were set up,respectively.Cell proliferation was detected by MTT assay,cell apoptosis was detected by flow cytometry,cell migration ability was detected by scratch assay,and cell invasion ability was detected by Transwell assay.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of miR-192 and WNT family member 2B(WNT2B)in each group.Results The survival rate and monoclonal number of SW1116 CC cells in group B were(57.32± 6.19)％and(284.59±15.08),which were lower than(76.21±8.23)％and(601.47±23.16)in group A and(89.52±10.62)％and(2 150.68±34.79)in group C,while the apoptosis rate in group B was(20.52± 2.52)％,which was higher than(13.78±1.62)％in group A and(11.62±1.41)％in group C.The survival rate and number of monoclonal formation of SW1116 CC cells in group C were higher than those in group A,while the apoptosis rate was lower than that in group A(all P＜0.05).The scratch width of SW1116 CC cells in group B was(785.10±46.18)mm,which was higher than(601.32±33.21)mm in group A and(326.99± 17.48)mm in group C,while the scratch width in group C was lower than that in group A.The number of per-forating cells in group B was(624.67±19.05),which was lower than(875.23±27.30)in group A and(1 204.17±34.59)in group C,and the number of perforating cells in group C was higher than that in group A(all P＜0.05).The relative expression level of miR-192 mRNA in SW1116 CC cells in group B was(3.01± 0.26),which was higher than(1.87±0.20)in group A and(0.97±0.23)in group C,and the relative expres-sion level of miR-192 mRNA in group C was lower than that in group A.The expression level of WNT2B mR-NA in group B was(2.16±0.26),which was lower than(4.11±0.50)in group A and(6.08±0.72)in group C,and the expression level of WNT2B mRNA in group C was higher than that in group A(all P＜0.05).Con-clusion miR-192 could inhibit the malignant evolution of CC,and one of its main mechanisms may be related to the regulation of WNT2B expression.
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Chronic pelvic inflammatory disease(CPID)is a common chronic inflammatory disease in women,and has a long course and is easy to relapse.Danggui Shaoyao Powder is from Jin Gui Yao Lve(Synopsis of the Golden Chamber),which was a commonly-used formula for the treatment of women's abdominal pain in ancient medical records.It is now often used in the treatment of CPID and has achieved satisfactory therapeutic effect.The article summarizes and analyzes the achievements in the clinical research and experimental study of Danggui Shaoyao Powder in the treatment of CPID over the past 10 years,and invesigates the clinical efficacy of Danggui Shaoyao Powder in the treatment of CPID and its therapeutic mechanism.In the field of clinical studies,Danggui Shaoyao Powder for the treatment of CPID was used by modification,or alone,or in combination with antibiotics and Chinese medicine external treatment,and its combined use was effective on significantly improving the indicators of inflammatory response and immune function,alleviating the clinical signs and symptoms such as pain,and did not increase the incidence of adverse reactions compared with the application of western medicines alone.In the field of experimental studies,Danggui Shaoyao Powder played the therapeutic role in CPID by decreasing the adhesion of endothelial cells,regulating the degradation of extracellular matrix,improving the level of inflammatory factors,and down-regulating the expression of proteins related to the nuclear factor κB(NF-κB)pathway.
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Objective To discuss the clinical efficacy and safety of bilateral internal iliac artery Fogarty balloon occlusion in uterine curettage for patients with cesarean scar pregnancy(CSP).Methods The clinical data of a total of 80 CSP patients,who were admitted to the Fuyang People's Hospital of China between January 2021 and September 2022 to receive treatment,were retrospectively analyzed.The patients were divided into the observation group(n=40)and the control group(n=40).For the patients of the observation group,the hysteroscopic uterine curettage was carried out under the situation of bilateral internal iliac artery Fogarty balloon occlusion and during the operation the internal iliac artery was intermittently blocked.The embryo was removed,and the hemostasis was accomplished by electrocoagulation or surgical suture.For the patients of the control group,the hysteroscopic uterine curettage was performed within 1-2 days after uterine artery embolization(UAE).The digital subtraction angiography(DSA)fluoroscopy time,body surface radiation dose,blood loss during uterine curettage,time spent for uterine curettage,length of hospital stay,and postoperative follow-up results were compared between the two groups.Results Successful uterine curettage was accomplished and the uterus was retained in all the patients.In the observation group,no balloon-related complications occurred.In the control group,all the 40 patients developed different degrees of fever,pain at uterine area,and other post-embolization symptoms after UAE.In the observation group and the control group,the DSA fluoroscopy time was(9.2±1.1)seconds and(1 273.6±141.1)seconds respectively,the body surface radiation dose was(7.7±0.8)mGy and(1 503.8±101.8)mGy respectively,the differences between the two groups were statistically significant(both P＜0.05);the blood loss during uterine curettage was(30.3±14.7)mL and(27.5±13.2)mL respectively,the time spent for uterine curettage was(41.6±16.2)min and(42.8±15.0)min respectively,the differences between the two groups were not statistically significant(both P＞0.05);the length of hospital stay was(6.0±0.7)days and(7.3±0.8)days respectively,the difference between the two groups was statistically significant(P＜0.05).All patients were followed up for more than 3 months,the time of β-hCG turning to negative,time of vaginal bleeding,time of menstruation returning to normal,and patient satisfaction rate in the observation group were(21.1±2.4)days,(8.2±1.1)days,(29.5±2.2)days and 95.0%(38/40)respectively,which in the control group were(24.6±3.3)days,(13.6±2.6)days,(46.7±7.3)days and 67.5%(27/40)respectively,the differences in the above indexes between the two groups were statistically significant(all P＜0.05).Conclusion In performing uterine curettage for CSP patients,both bilateral internal iliac artery Fogarty balloon occlusion and UAE can significantly reduce the intraoperative blood loss,but bilateral internal iliac artery Fogarty balloon occlusion is superior to UAE in reducing radiation dose,in shortening the patient's hospital stay,the time of β-hCG turning to negative,the time of vaginal bleeding and the time of menstruation returning to normal,and in improving the patient satisfaction rate.
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Objective To evaluate the postoperative analgesia efficacy and clinical safety of hydro-morphone patients-controlled intravenous analgesia(PCIA)in patients with scar pregnancy after auxiliary uterine artery embolization(UAE).Methods A total of 116 patients with scar pregnancy,who received auxiliary UAE at the Fuyang Municipal People's Hospital of China between January 2021 and September 2022,were enrolled in this study.According to the intravenous self-controlled analgesic drugs used after UAE,the patients were randomly and equally divided into observation group(n=58)and control group(n=58).Ten minutes before the procedure,intravenous injection of 2 mg hydromorphone(observation group)or 2 μg/kg sufentanyl(control group)was performed,and the PCIA pump was connected.In the observation group,the mixed solution of 10 mg hydromorphone+100 mg flurbiprofen axetil+100 mL saline was put in the analgesic pump,while in the control group,the mixed solution of 2 μg/kg sufentanyl+flurbiprofen axetil 100 mg+100 mL saline was put in the analgesic pump.The post-UAE 0.5-h,4-h,8-h,12-h,24-h and 48-h visual analogue scale(VAS)scores,the Bruggrmann comfort scale(BCS)scores,the number of pressing analgesic pump times within postoperative 48 hours,the used dosage of analgesic drugs,the adverse reactions,and the incidence of postoperative complications were recorded.Results The difference in the post-UAE 0.5-h VAS scores between the observation group and the control group was not statistically significant(P＞0.05),while the post-UAE 4-h,8-h,12-h,24-h and 48-h VAS scores in the observation group were significantly lower than those in the control group,and the differences were statistically significant(all P＜0.05).The post-UAE 0.5-h,4-h,8-h,12-h,24-h and 48-h BCS scores in the observation group were significantly higher than those in the control group,and the differences were statistically significant(all P＜0.05).The number of pressing analgesic pump times and the used dosage of analgesic drugs within postoperative 48 hours in the observation group were lower than those in the control group,and the differences were statistically significant(all P＜0.05).No statistically significant differences in the complications such as drowsiness,skin itching,hypoxia,or respiratory depression,etc.existed between the two groups,while the difference in the incidence of adverse reactions between the two groups was statistically significant(P＜0.05).Conclusion Hydromorphone and sufentanil PCIA can relieve the pain in scar pregnancy patients after UAE.Hydromorphone is superior to sufentanil in reducing the number of pressing analgesic pump times within postoperative 48 hours,reducing the used dosage of analgesic drugs,and decreasing the incidence of adverse reactions,therefore,hydromorphone PCIA has a certain promotion value.(J Intervent Radiol,2024,33:240-244)
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Objective To investigate the changes of sex hormone levels in polycystic ovary syndrome(PCOS)in infertile population after the assisted reproductive technology treatment,and to provide an evidence for the choice of the treatment.Methods The medical data of patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2016 to June 2021 were collected and divided into PCOS group(103)and non-PCOS group(589)according to whether they were diagnosed with PCOS,and the sex hormone changes of the two groups were compared.Results The patients in PCOS group were younger and had the higher BMI,more sinus follicles,higher AMH value,and lower total Gn usage.The number of LH/FSH>2 in PCOS group was higher than that in non-PCOS group(P<0.05).After the treatment,LH in both groups decreased,FSH,E2 and(P<0.05)increased;The difference of LH and E2 before and after the treatment in PCOS group was greater than that in non-PCOS group<0.05).Conclusion Compared with non-PCOS infertile patients,the changes of sex hormone indexes in PCOS infertile patients before and after the treatment were more obvious.In order to obtain the better clinical effect in patients with polycystic ovaries,it is recommended to pay attention to the changes of related sex hormone levels in the course of subsequent treatment,and choose a reasonable treatment plan.
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Objective To compare and analyze the gene mutation of EGFR of bronchoalveolar lavage fluid(BALF)exosome,serum and lung cancer tissue specimens of patients with advanced non-small cell lung cancer(NSCLC)and assess whether the BALF exosome specimens are suitable for screening before clinical targeted therapy,to provide new ideas and screening methods for early individualized treatment of advanced NSCLC patients.Methods BALF exosomes,serum and lung cancer tissue specimens EGFR gene mutations of 78 cases with advanced NSCLC were detected by using amplification refractory mutation system(ARMS)method in Department of Respiratory and Critical Care Medicine in our hospital from May 2021 to May 2023,and the results were retrospec-tively analyzed.A comparative analysis of the specimens was conducted using lung cancer tissue specimens as bench-marks.Results A total of 33,25 and 38 cases of EGFR gene mutation and 42,53 and 40 cases of EGFR wild type were detected in BALF exosomes,serum and lung cancer tissues specimens respectively.The mutation rate of EGFR gene was 42.3%(33/78,32.1%(25/78)and 48.7%(38/78)in BALF exosomes,serum and lung cancer tissues specimens respectively.EGFR detection showed no results in 3 cases and the false-negative rate was 6.4%(5/78)in BALF specimen,and false-negative rate was 16.7%(13/78)in serum.The detection coincidence rate of EGFR mutation was 86.8%(33/38)in BALF exosomes specimen,and 65.8%(25/38)in serum.Conclusions EGFR gene mutation rate in BALF exosome specimen is consistent with that in serum and lung cancer tissue samples,showing no statistical significance(P>0.05).It is superior to serum specimen and suitable for patient screening before targeted therapy and provides new ideas and screening methods for early individualized treatment decisions of advanced NSCLC patients.
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Objective To observe and evaluate the protective effect of desflurane post-conditioning on myocardial injury during cardiopulmonary bypass and its influence on patients'postoperative recovery.Methods A total of 200 patients in need of cardiac surgery were selected as the experimental subjects,who were aged from 20 to 65 years old,and divided into ASA Ⅱ-Ⅲ and NYHA Ⅱ-Ⅲ by endotracheal intubation and extracorporeal circulation method under general anesthesia.The patients were randomly divided into desflurane post-treatment group(experi-mental group,group D)and control group(group C)after selection.With the successive opening of the aorta and superior vena cava,group D were given 5%desflurane by inhalation with mechanical ventilation.While group C inhaled pure oxygen without inhaling desflurane.The depth of intraoperative anesthesia was maintained between 40～50 during the operation.Radial artery blood was collected from patients in 24 h before surgery(T0),immediately after intubation(T1),and 1 h(T2),6 h(T3),12 h(T4)and 24 h(T5)after aortic opening to achieve the determi-nation of troponin I(cTnI)and creatine kinase isoenzyme MB(CK-MB).On the premise of obtaining the informed consent of the patient,about 50 mg of right atrial appendage tissue was collected before aortic intubation(T1.5)and 1 hour after aortic opening(T2)to determine the apoptosis rate.Results(1)cTnI in group C at the time of T2,T3,T4 and T5 was apparently higher than group D(P<0.05).(2)CK-MB in group C at the time of T3 was apparently higher than group D(P<0.05).(3)The myocardial tissue results showed that there was a lower apoptosis rate in experimental group at the time of T2(P<0.05).Conclusion Desflurane post-conditioning has a myocardial protec-tive effect during cardiac surgery under cardiopulmonary bypass.
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BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.
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Objective In order to explore the influence and effect of case teaching method based on real patients in oto-rhinolaryngology on clinical practice ability of general practice.Methods 96 trainees of general practice in otolaryngology de-partment from January 2018 to January 2021 were randomly divided into two groups:a CBL group and a control group.In the CBL group,CBL teaching method was adopted based on real patients in Otorhinolaryngology.Conventional teaching method was used in the control group.Results The theoretical scores of written test and the examination of clinical skill operation scores of the CBL group and the control group were analyzed.There was significant difference between the two groups(P＜0.05).The students in CBL group were more satisfied with clinical thinking ability,analysis and problem solving ability,active learning abil-ity,learning efficiency,teacher-student interaction,doctor-patient communication ability and consultation skills than the control group.There was significant difference between the two groups(P＜0.05).Conclusion The CBL teaching method can obvi-ously improve the learning enthusiasm and clinical practice ability of general resident training doctors.The teaching quality has been significantly improved.It is of great value to cultivate excellent general practitioners.
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Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.
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ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.
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ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L-1）， Coptidis Rhizoma group（B group， 38.4 g·L-1）， processed Euodiae Fructus group（C group， 5.88 g·L-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（Cmax） of Ber， Pal， Evo， and Rut were the highest and time to peak（tmax） were the lowest in the liver of A group. In plasma， the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group， tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver， compared with B-D groups， Cmax values of 5 representative components except Pae were elevated， AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t1/2） of each representative components in A group was elevated and tmax was decreased， and Cmax of each representative ingredient except Pal was decreased， AUC0-t values of Ber and Pal were increased， whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.
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As a new type of immunosuppressant，iguratimod can mediate the anti-inflammatory signaling pathway by inhibiting the proliferation of inflammatory cells and reducing the release of inflammatory cytokines， and play the role of anti-inflammatory. It can affect the proliferation of immune cells and the expression of immune factors，reduce the production and deposition of immune complexes in the body，and play the role of immune regulation. It can regulate bone metabolism by mediating signaling pathways such as Wnt/β-catenin，Toll-like receptor 4/nuclear factor-κB and osteoprotegerin/nuclear factor-κB receptor activating factor ligand， and play a role in bone protection. It can inhibit pulmonary fibrosis by inhibiting the expression of transforming growth factor β1/ Smad2/3 signaling pathway，tumor necrosis factor-α，interleukin-1，interleukin-6，matrix metalloproteinase-9 and other inflammatory cytokines in lung tissue，and inhibiting the expression of collagen and fibronectin. Its efficacy and safety have been confirmed in the clinical application of rheumatoid arthritis and primary Sjogren syndrome and included in the diagnosis and treatment of the disease. It has also shown good efficacy in the clinical application of other connective tissue diseases such as systemic lupus erythematosus and ankylosing spondylitis，and no obvious safety risks have been found.
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Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L
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During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.