Mesangial proliferation is a basic pathologic process of many kidney diseases,mesangial proliferative glomerulonephritis(MsPGN) is the common pathological type.The pathogenesis of MsPGN still remains unclear.Recently,cytokines of fractalkine,interleukin and TGF-β gradually become hotspot in the pathogenesis of MsPGN.Studies shows that a variety of cytokines play an important roles in the development of MsPGN and the mechanism has been gradually clarified.Certain progress has been made in treatment,and more profound understanding of mycophenolate mofetil has been received,the treatment of the MsPGN as manifestations with refractory nephrotic syndrome has been achieved good effect.This review is based on the recent years of the primary non-IgA MsPGN progress.

Objectives To evaluate the efficacy and safety of single-incision versus conventional laparoscopic cholecystectomy.Methods We searched electronic databases (PubMed,EMBASE,Cochrane Library,Chinese Biomedicine databases) from January 2000 to April 2012.Personal contact with experts in the field of laparoscopic cholecystectomy was performed to identify further potentially relevant clinical trials.Randomized controlled trials conducted on single-incision versus conventional laparoscopic cholecystectomy were analysed to compare conversion rates,blood loss,operation time,postoperative complications,wound satisfaction score,postoperative pain score and postoperative duration of hospitalization.Data were extracted by two reviewers independently.Statistical analysis was performed by using the RevMan 5.1 software.Results Twelve studies involving 915 patients met the inclusion criteria.When compared with conventional laparoscopic cholecystectomy (LC),the singleincision laparoscopic cholecystectomy (SILC) group showed no significant difference in conversion rate (OR=0.70,95％CI: 0.13～3.77,P=0.68),postoperative complications (OR=1.13,95％CI:0.72～1.78,P＝0.59) and postoperative pain scores (WMD＝-0.18,95％CI:-0.78～-0.43,P=0.57) . There was a significant increase in operative blood loss (WMD ＝ 1.43,95 ％ CI: 0.09 ～2.78,P＜0.05),increase in operative time (WMD=16.79,95％CI: 9.05～24.52,P＜0.01),but an increase in wound satisfaction score (WMD=1.28,95％CI..1.09～1.47,P＜0.01).The postoperative duration of hospitalization was significantly shorter (WMD =-0.30,95％ CI:-0.58 ～-0.02,P＜0.05).Conclusions Current evidence suggests that there is no significant difference in conversion rate or postoperative complications between SILC and LC.Although SILC requires a longer operative time and there is more blood loss when compared with LC,the SILC is superior in wound satisfaction score and in duration of hospitalization.

Objective To find out a more rational pathological classification criteria for renal injury in patients with type 2 diabetes mellitus. Methods The renal clinicopathological features of forty-nine type 2 diabetic patients with maeroalbuminuria were collected and were compared retrospectively. The patients without diabetic renal disease were excluded. According to the pathological features, the patients were divided into two groups: typical diabetic glomerulopathy (DG) and atypical diabetes-related renal disease (ADRD). Results The renal biopsy revealed DG accounted for 59.2% of the patients, while the remaining 40.8% presented atypical renal injury defined as ADRD. In DG group, volume fraction of mesangium per glomerulus, glomerular basement membrane width, atrophic tubules index, intersititium injury index and prevalence of hyalinization of renal arteriole were higher; podocyte density per glomerulus was lower; duration of type 2 diabetes was longer; the level of fast blood glucose, systolic blood pressure, mean arterial pressure, proteinuria and prevalence of diabetic retinopathy (DR) were higher; glomerular filtration rate (GFR) was lower. In ADRD group, body mass index and prevalence of obesity were higher; dyslipidemia was more severe. GFR was negatively correlated with glomerular global sclerosis rate in both DG and ADRD group. Proteinuria was positively correlated with volume fraction of mesangium per glomerulus in DG. No correlation between proteinuria and pathological features was found in ADRD. DR (94.8%) and duration of type 2 diabetes over five years (90.7%) had high negative predictive value for DG. Conclusions Renal injuries in type 2 diabetes patients are heterogeneous. ADRD is an atypical renal injury in type 2 diabetes patients whieh is different from DG. DR and duration of diabetes are more helpful in predicting DG separating from ADRD.

Objective To study the pathologic pattern and clinical feature of type 2 diabetes mellitus complicated with chronic kidney diseases (CKD). Methods Clinicopathological features of 155 type 2 diabetic patients complicated with CKD were collected and analyzed retrospectively. The patients were divided into four groups: typical diabetic glomerulopathy (DG),atypical diabetes-related renal disease (ADRD), non-diabetic renal diseases (NDRD) and DG complicated with NDRD. Results Renal biopsies revealed DG accounted for 18.7% of the patients, ADRD accounted for 12.9%, NDRD accounted for 60.0%, and DG complicated with NDRD accounted for 8.4%. In DG group, duration of type 2 diabetes was longer;the level of fast blood glucose, systolic blood pressure, mean arterial pressure and prevalence of diabetic retinopathy (DR) were higher;proteinuria was heavier and evaluated glomerular filtration rate (eGFR) was lower. In ADRD group, body mass index and prevalence of obesity were higher;dyslipidemia was more severe. Gross hematuria and acute renal insufficiency could be only found in NDRD group.Without DR, duration of diabetes under 5 years, gross hematuria, acute renal insufficiency,evidences of autoimmune diseases and proteinuria≥3.5 g/24 h but eGFR ≥60 ml/min were specific valuable predictors for NDRD. Conclusions Renal injuries in type 2 diabetic patients are structural heterogeneous, in which NDRD is more common and is different from ADRD and DG.Renal biopsy should be considered when type 2 diabetic patients complicated with CKD present at least one characteristic as follows: duration of diabetes under 5 years, without DR, history of gross hematuria, acute decrease of renal function, evidences of autoimmune diseases and proteinuria ≥ 3.5 g/24 h but eGFR ≥ 60 ml/min.

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.

Objective To investigate the influence of atosiban on the pregnancy outcome in patients with repeated implantation failure(RIF)in blastcyst thawed embryo transfer(bTET) Methods From January 2014 to December 2015,a total of 262 RIF patients undergoing bTET were retrospectively studied. They were divided into study group with a single bolus dose (6.75 mg/0.9 mL,iv) of atosiban before bTET (n = 94),and control groupwithout atosiban(n = 168). Results The clinical pregnancy rate(57.41%),implantation rate(38.41%) and living-birth rate(46.81%) of study group were significantly higher than those of control group (41.12%, 28.32% and 33.93% respectively;P < 0.05). Although the abortion rate of study group was higher than that of control group(14.82% vs 13.04%),both the ectopic pregnancy rate(3.70%) and the multiple pregnancy rate (16.67%) were lower than those of control group(5.79% and 17.39%),and there was no statistical difference (P > 0.05). Conclusion Atosiban treatment before embryo transfer may improve pregnancy outcomes of RIF patients in bTET.

Currently, killed-virus and modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are used to control porcine reproductive and respiratory syndrome. However, both types of vaccines have inherent drawbacks; accordingly, the development of novel PRRSV vaccines is urgently needed. Previous studies have suggested that yeast possesses adjuvant activities, and it has been used as an expression vehicle to elicit immune responses to foreign antigens. In this report, recombinant Kluyveromyces lactis expressing GP5 of HP-PRRSV (Yeast-GP5) was generated and immune responses to this construct were analyzed in mice. Intestinal mucosal PRRSV-specific sIgA antibody and higher levels of IFN-gamma in spleen CD4+ and CD8+ T cells were induced by oral administration of Yeast-GP5. Additionally, Yeast-GP5 administered subcutaneously evoked vigorous cell-mediated immunity, and PRRSV-specific lymphocyte proliferation and IFN-gamma secretion were detected in the splenocytes of mice. These results suggest that Yeast-GP5 has the potential for use as a vaccine for PRRSV in the future.
Administration, Oral ; Animals ; Antibodies, Viral/*immunology ; B-Lymphocytes/immunology/virology ; Enzyme-Linked Immunosorbent Assay ; *Immunity, Cellular ; *Immunity, Mucosal ; Injections, Subcutaneous ; Kluyveromyces/genetics ; Mice ; Mice, Inbred BALB C ; Porcine respiratory and reproductive syndrome virus/*immunology ; Recombinant Proteins/genetics/immunology ; T-Lymphocytes/immunology/virology ; Viral Envelope Proteins/*genetics/*immunology ; Viral Vaccines/administration & dosage/*pharmacology

CCAAT enhancer binding protein β (C/EBPβ), as a nuclear transcription factor necessary for the development of liver, airway epithelium, and adipose tissue, plays a vital role in physiological processes related to cell proliferation, apoptosis, and differentiation. However, the up-regulation of C/EBPβ activates signal pathways related to inflammatory response, epithelial-mesenchymal transition, cell proliferation and invasion, immune response, and angiogenesis by regulating a series of downstream genes transcription promotes the development of lung diseases. Therefore, targeting C/EBPβ may be a potential treatment strategy for lung diseases. This paper summarizes the regulatory effects of C/EBPβ and related signaling pathways in lung infection, asthma, chronic obstructive pulmonary disease, lung injury, pulmonary fibrosis, and lung cancer to provide a theoretical basis for the precision medicine of lung diseases.

Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

ObjectiveTo investigate the effects of the volatile oil of Linderae Radix on the apoptosis and autophagy of human gastric cancer cell line AGS， and to explore the regulatory role of adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway in this process. MethodThe volatile oil of Linderae Radix was extracted by steam distillation， and the effect of the volatile oil on the viability of AGS cells was detected by thiazolyl tetrazolium （MTT） colorimetry. The optimal intervention dose and time were determined according to the half maximal inhibitory concentration （IC₅₀） for subsequent research. The blank， low， medium， and high-dose volatile oil （0， 15， 30， 60 mg·L^-1） groups and the positive drug cyclophosphamide （CTX， 350 mg·L^-1） group were designed. AGS cells were treated with different doses of volatile oil for 48 h. The changes in cell proliferation， cycle， and migration were measured by colony formation assay， flow cytometry， and cell scratch test， respectively. Hematoxylin-eosin （HE） staining was employed to observe the changes of cell morphology， Annexin-V/propidium iodide （PI） double staining to measure the apoptosis， and acridine orange （AO） staining to measure the autophagy level of the cells. Western blotting was employed to determine the expression of the autophagy effectors Beclin-1， p62， microtubule-associated protein 1-light chain 3 （LC3）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3， cleaved poly ADP-ribose polymerase （PARP）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultCompared with the blank group， 24 h and 48 h of intervention with the volatile oil of Linderae Radix inhibited the viability of AGS cells in a concentration- and time-dependent manner （P<0.05， P<0.01）. Compared with the blank group， the volatile oil decreased the cell proliferation and migration （P<0.05， P<0.01） and blocked the AGS cell cycle in G₂/M phase （P<0.05， P<0.01） in a concentration-dependent manner. The cells treated with the volatile oil became spherical and smaller， with the formation of apoptotic bodies and increased apoptosis rate （P<0.05， P<0.01）. As the dose of the volatile oil increased， the number of autophagosomes increased and the red fluorescence gradually enhanced， indicating the elevated level of autophagy. Compared with the blank group， different doses of volatile oil up-regulated the protein levels of Beclin-1， LC3 Ⅱ/LC3 Ⅰ， cleaved Caspase-3， cleaved PARP， Bax/Bcl-2， and AMPK （P<0.05， P<0.01） and down-regulated the protein levels of p62 and p-mTOR （P<0.05， P<0.01）. ConclusionThe volatile oil of Linderae Radix induces the apoptosis and exerts the autophagy-mediated growth inhibition of AGS cells by regulating the AMPK/mTOR signaling pathway.