Toll-like receptor 4 (TLR4) plays an important role in inflammation and immune response.MicroRNAs (miRNAs) are involved in the regulation of TLR4 signaling pathway in multiple levels and various molecules,which play an important role in inflammatory reaction.A variety of miRNAs are involved in the regulation of TLR4 signaling pathway,and the TLR4 signaling pathway can induce a variety of miRNAs.Chronic diseases such as diabetes,Alzheimer's disease and cardiovascular disease are closely related to inflammatory response.The regulatory role of TLR4 signaling related miRNAs has attracted much attention in inflammatory diseases.In this review,the research progress of TLR4 signaling pathway related miRNAs in the regulation of inflammatory response is summarized,which provides a new research direction for the clinical diagnosis and treatment of inflammatory response related diseases.

AIM:To investigate the effects of celecoxib,a selective cyclooxygenase-2 inhibitor,on antioxidative capability and apoptosis of cardiac myocytes after myocardial infarction.METHODS:24 New Zealand rabbits were divided into three groups randomly(8 in each group):sham-operated group(sham group),myocardial infarction group(MI group),celecoxib group(Cele group,10 mg kg-1?d-1,qd,with the drugs gastric gavage for six weeks).The NO concentration,total antioxidative capability(T-AOC),the activity of constitutive nitric oxide synthase(cNOS)and inducible NOS(iNOS)in cardiac tissue homogenate,adjacent to the infracted area,were detected.The pathological changes were observed by light microscope and electron microscopy.The expressions of Bcl-2 and Bax protein in myocytes were observed using immunohistochemistry,and the degree of apoptosis were examined by TUNEL.RESULTS:Cardiac tissue in MI group presented interstitial edema,fibroplastic proliferation,inflammatory cellular infiltration,and vacuolar degeneration in cardiac myocytes.The results of electron microscopy showed that myocytes presented more changes caused by ischemic injury:widened interspace of myofibril,disordered myofibrillae,focal lysis of myofilament,ectasia of sarcoplasmic reticulum.In Cele group,the pathological changes were light,the NO-_2/NO-_3 concentration,the activity of iNOS were lower(P

Objectives To investigate the etiology, renal pathology, treatment, and prognosis of children's urinary system injury after hematopoietic stem cell transplantation (HSCT). Methods Clinical data of 81 children with urinary dysfunction after HSCT admitted to the Hematology Department in Children's Hospital of Soochow University were analyzed, and relevant literatures were reviewed. Results In 81 cases (50 males and 31 females), the age ranges from 8 months to 17 years old. Thirty cases (37%) with prerenal injury were recovered after active rehydration and other symptom specific treatment. There were 9 (11.1%) children with renal injury, four cases were given up therapy or transferred to other hospitals, thus lead to an unknown prognosis. Kidney biopsy was performed in the remaining five cases for pathological investigation. After active symptom-speific and etiology-based treatment, serum creatinine and glomerular filtration rate of four cases return to normal. But in the long-term follow-up,one case died of recurrence of primary disease, reinfusion of hematopoietic stem cell combined with renal failure. The remaining 3 patients were with chronic kidney disease (CKD). One case with renal thrombotic microangiopathy was in the chronic dialysis. Postrenal renal injuries were mainly hemorrhagic cystitis (28.4%) and urinary tract infection (16%). After a large dose of rehydration, urine alkalization and anti-infection therapy, they were recovered in the short term with a good prognosis. Conclusions Urinary injury after HSCT is mainly divided into three categories: prerenal, renal and postrenal, in which renal injury is prone to frequent recurrence.

Objectives To detect the level of soluble programmed death 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in serum and urine of children with primary nephrotic syndrome (PNS),and explore its clinical significance.Methods From July 2017 to November 2017,children with PNS admitted to the Children's Hospital Affiliated to Soochow University were divided into onset group (36 cases) and remission group (33 cases).Thirty healthy children who underwent medical examination for enrollment,undersize or overweight in the outpatient department of pediatric health care and inpatient department of Endocrinology were selected as healthy control group.Serum and urine samples were collected,in which the levels of sPD-1 and sPD-L1 were detected by enzyme-linked immunosorbent assay (ELISA).The correlation between serum and urine sPD-1,sPD-L1 levels and lymphocyte subsets,urinary protein were analyzed by Pearson and Spearman correlation analysis.Results The level of sPD-1 in serum was lower in remission group than those in healthy controlgroup [1.60(0.48,8.15) ng/ml vs 7.38(2.15,19.02) ng/ml,P ＜ 0.01].The level of urinary sPD-1 in onset group was higher than that in remission group [1.21(0.61,2.56) pg/μg vs 0.51(0.31,0.97) pg/μg,P ＜0.001] and healthy control group [1.21(0.61,2.56) pg/μg vs 0.82(0.34,1.15) pg/μg,P ＜ 0.01].The levels of sPD-L1 in serum and urine were higher in onset and remission group than those in healthy control group (P ＜ 0.001).The level of sPD-1 in the serum was positive correlated with the numbers of CD3+,CD3+CD4+,CD3+ CD8+ T lymphocytes and CD3-CD19+,CD19+CD23+ B lymphocytes (r=0.537,0.478,0.454,0.429 and 0.374;P=0.002,0.008,0.012,0.018 and 0.042).The level of sPD-1 in the urine had positive relation with the ratio of 24 hours urinary albumin and weight (24 h UmAlb/Wt),N-acetylglucosaminidase and urinary creatinine (UNAG/Cr) and β2 microglobulin and urinary creatinine (Uβ2MG/Cr) (r=0.409,0.588 and 0.276;P=0.016,0.000 and 0.032).Conclusions The dynamic changes of sPD-1 and sPD-L1 in serum and urine suggested that PD-1/PD-L1 signaling pathway is involved in the development process of childhood primary nephrotic syndrome.

Objective:To investigate the effectiveness and safety of bortezomib combined with conventional chemotherapy regimens for treatment of relapsed/refractory acute B lymphoblastic leukemia (B-ALL).Methods:Twenty patients with relapsed/refractory B-ALL treated with bortezomib combined with chemotherapy in Jiaozuo People's Hospital Affiliated to Xinxiang Medical College, Jiaozuo Coal Industry Group Central Hospital and the Second People's Hospital of Jiaozuo from September 2021 to June 2022 were collected, and their treatment response and prognosis were retrospectively analyzed.Results:The median age of the 20 patients was 49.5 years old (25.0-58.5 years old); 12 were male and 8 were female; 12 were relapsed and 8 were refractory. All patients completed 1 course of bortezomib (1.6 mg/m 2, subcutaneous injection on days 2 and 16) combined with chemotherapy. Before bortezomib treatment, there were 0 case of complete remission (CR), 7 cases of partial remission (PR) and 13 cases of non-remission (NR) in 20 patients, the objective remission rate (ORR) was 35% (7/20), and all were positive for minimal residual disease (MRD). After bortezomib treatment, there were 13 cases of CR, 3 cases of PR and 4 cases of NR, and the ORR was 80% (16/20); the MRD of all patients decreased, among which 13 cases (65%) turned to negative; the differences were statistically significant when comparing CR rate, ORR and MRD negative conversion rate before and after bortezomib treatment ( χ2 values were 65.41, 8.83 and 19.30, all P < 0.05). Four of the 20 patients developed central nervous system infiltration despite bone marrow remission, and one died from post-chemotherapy infection. Myelosuppression occurred in all patients, the incidence of infection was 90% (18/20), and the incidence of digestive system adverse effects was 75% (15/20). Conclusions:Bortezomib combined with conventional chemotherapy regimens is effective and well tolerated in the treatment of relapsed/refractory ALL, and has the potential to enable patients with multi-drug resistant relapse to overcome resistance and to achieve deep remission.

Objective:To investigate the behavioral, electroencephalographic, and cognitive functional differences in drug-resistant epileptic rat models of cognitive impairment prepared by intraperitoneal injection of lithium chloride-pilocarpine followed by intracranial injection of pilocarpine or carbamylcholine.Methods:One hundred and sixty adult male SD rats were randomly divided into normal control group ( n=10), lithium chloride-pilocarpine group (establishing epileptic rat models by intraperitoneal injection of lithium chloride-pilocarpine, n=50), pilocarpine-pilocarpine group (intracranial injection of pilocarpine after intraperitoneal injection of lithium chloride-pilocarpine, n=50)and pilocarpine-carbamylcholine group (intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine, n=50). Frequency and duration of spontaneously recurrent seizures (SRSs) were observed by video monitoring system, and 2 weeks after that, phenobarbital and phenytoin sodium were injected intraperitoneally to screen drug-resistant models. Frequency and amplitude of the epileptic waves in EEG were recorded by BL-420 Bio-signal Acquisition and Processing System. Novel object recognition experiment was used to detect the novel exploration, Y-maze free exploration experiment and new and different arm experiment were used to detect the spatial recognition and memory ability, and Morris water maze experiment was used to detect the spatial memory ability. Results:(1) Twenty-four rats (48.00%) survived in the lithium chloride-pilocarpine group, 25 (78.00%) in the pilocarpine-pilocarpine group, and 21 (65.62%) in the pilocarpine-carbamylcholine group; and ultimately 7, 9, and 8 drug-resistant epileptic rat models were identified, respectively; frequency and duration of SRSs in the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group were significantly higher/longer than those in the lithium chloride-pilocarpine group ( P<0.05). (2) The pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly higher amplitude of the epileptic waves in EEG compared with the lithium chloride-pilocarpine group ( P<0.05); the frequency of the epileptic waves in EEG increased gradually in the lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group ( P<0.05). (3) Discrimination index, accuracy, ratio of distance traveled in novel arm to total distance, and time of novel arm entries gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). (4) Compared with the normal control group, the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly decreased frequency in crossing the original platform ( P<0.05); compared with the normal control group, lithium-pilocarpine chloride group and pilocarpine-pilocarpine group, the pilocarpine-carbamylcholine group had statistically shorter distance of target quadrant activity ( P<0.05); number of entries in the target quadrant gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). Conclusion:Drug-resistant epileptic rat models established by intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine have high survival rate, high SRSs rate, and severe cognitive impairment, which is suitable for studying drug-resistant epilepsy combined with cognitive impairment.

AIM: To assess the therapeutic effect of lienal polypeptide injection (LPI) on bone marrow suppression and poor immunity in Kunming (KM) mice after the intervention of chemotherapy drug carboplatin (CBP), as well as its potential mechanisms. METHODS: KM female mice were randomly divided into control group, model group, low-dose lienal polypeptide, and high-dose lienal polypeptide treatment groups. On day 1, mice in the treatment group and model group were subjected to intraperitoneal single injection of carboplatin (70 mg / kg), to induce chemotherapy-induced bone marrow suppression in mice, while the control group was intervened with normal saline. From Day 2 to Day 16, the treatment groups received daily intraperitoneal injections of lienal polypeptide (60 mg · kg

Objective: To investigate the inhibitory effect of macrophage foaming by Yinlan Tianzhi formula (YLTZ) and to explain its effects on lipid-induced inflammation and LXRα-ABCA1 signal pathway. Methods: The model of macrophage foaming was induced by incubating the RAW264.7 cells or BMMs with ox-LDL (50 mg·L-1). The serum containing YLTZ was prepared. The cells were divided into blank group, model group, and drug group. After drug intervention, MTT method was used to detect cell proliferation. The lipid accumulation in cells was observed by oil red O staining, and GPO-PAP method was used to determine the total cholesterol content in cells. Protein and mRNA levels were determined by Western blot and RT- qPCR. Results: Compared with control group, after YLTZ treatment, the lipid level was significantly decreased, and the level of mRNA and protein of LXRα and ABCA1 were significant increased. The expression of inflammatory factor COX2 and iNOS was significantly decreased. Conclusion: YLTZ inhibits macrophage foaming through enhancing LXRα-ABCA1 pathway and suppressing of inflammatory response.

Objective To comprehensively analyze the clinical outcomes of total cavopulmonary connection (TCPC) in the treatment of functional single ventricle combined with heterotaxy syndrome (HS). Methods A retrospective analysis was conducted on the patients with functional single ventricle and HS who underwent TCPC (a HS group) in Guangdong Provincial People's Hospital between 2004 and 2021. The analysis focused on postoperative complications, long-term survival rates, and identifying factors associated with patient survival. Early and late postoperative outcomes were compared with matched non-HS patients (a non-HS group). Results Before propensity score matching, 55 patients were collected in the HS group, including 42 males and 13 females, with a median age of 6.0 (4.2, 11.8) years and a median weight of 17.0 (14.2, 28.8) kg. Among the patients, there were 53 patients of right atrial isomerism and 2 patients of left atrial isomerism. Eight patients underwent TCPC in one stage. TCPC procedures included extracardiac conduit (n=39), intracardiac-extracardiac conduit (n=14), and direct cavopulmonary connection (n=2). Postoperative complications included infections in 27 patients, liver function damage in 19 patients, and acute kidney injury in 11 patients. There were 5 early deaths. The median follow-up time was 94.7 (64.3, 129.8) months. The 1-year, 5-year, and 10-year survival rates were 87.2%, 85.3%, and 74.3%, respectively. After propensity score matching, there were 45 patients in the HS group and 81 patients in the non-HS group. Compared to the non-HS group, those with HS had longer surgical and mechanical ventilation time, higher infection rates (P<0.05), and a 12.9% lower 10-year survival rate. Multivariate Cox regression analysis identified asplenia was a risk factor for mortality (HR=8.98, 95%CI 1.86-43.34, P=0.006). Conclusion Compared to non-HS patients, patients with HS have lower survival rates after TCPC, and asplenia is an independent risk factor for the survival of these patients.