Aim: To study the effect of Eudragit S-100, a pH-responsive polymer, on protein refolding level, using recombinant human keratinocyte growth factor-2 (rhKGF-2) as a model protein. Methods: The refolding of rh-KGF-2 was performed by directly diluting denatured rhKGF-2 into a refolding buffer containing different concentrations of Eudragit. The ability of Eudragit S-100 to enhance protein refolding level was investigated using MTT assay, reverse phase HPLC, fluorescence emission spectroscopy and circular dichroism spectroscopy. Results: The addition of Eudragit S-100 in the refolding buffer significantly increased the rhKGF-2 refolding yield to 71%, when dilution refolding was conducted at 0. 5 mg/mL rhKGF-2. The outcome from the refolding study showed possibility of a special interaction between rhKGF-2 and Eudragit, suggesting that the refolding-enhancing ability of Eudragit S-100 was due to this interaction between Eudragit S-100 and rhKGF-2. Mean while, the result showed that the concentration of urea was also an important factor for the optimization of the refolding in the presence of Eudragit. Conclusion: Eudragit S-100 can significantly increase the refolding level of rhKGF-2.

Objective To analyze the changes and clinical significance of C-reactive protein (CRP)、hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) in different disease stage of multiple myeloma according the international staging system. Method Thirty untreated MM patients with complete clinical records were included in the stndy. The multiple myeloma patients were classified into three groups according to international staging system (ISS).Thirty megaloblastic anemia patients of similar age 、sex、hemoglobin level as the observation group.Resulets The levels of CRP (24.17±9.87 mg/L)、Hb (71.72±13.27 g/L) and ESR (105.94±27.73 mm/h) of stage Ⅲ patients were statistically different with stage Ⅰ ( CRP 8.54±1.97 mg/L; Hb 91.00±9.92g/L; ESR 73.57±20.53mm/h)、Ⅱ patients ( CRP 14.89±5.51 mg/L; Hb 91.29±8.32g/L; ESR 67.00± 15.56 mm/h) separately (P＜0.05).The levels of CRP (19.40±10.17 mg/L) and ESR (91.90±29.70 mm/h) in the MM patients were significantly higher than that in the observation group Ⅰ ( CRP 7.52±1.57mg/L; ESR 20.20±8.04mm/h) (P＜0.05 respectively).CRP and ESR level in MM patients positively correlated with myeloma cell proportion and β2-microglobulin level (P＜0.05), while Hb level negatively correlated with myeloma cell proportion and β2-microglobulin level (P＜0.05),Conclusion The levels of C-reactive protein、hemoglobin and erythrocyte sedimentation rate are closely associated with the development of multiple myeloma. C-reactive protein and hemoglobin are relatively sensitive response to disease than erythrocyte sedimentation rate. There is a clear clinical implication in detecting the patient' s condition for progress and the prognosis.

Microbiome dysbiosis is strongly associated with alcoholic liver disease(ALD).Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ALD.Importantly,targeting the microbiome has become a potential strategy for the prevention and treatment of ALD.In this review,we summarize the clinical evidence of microbiome dysbiosis in ALD patients,and experimental advances in microbiome and metabolomic functional changes in animals with different species and genetic back-grounds in ALD.We also summarize the studies in humanized intestinal microbiome and fecal micro-biota transplantation in mice.We introduce new developments in the studies on the role of the circulating bacterial microbiome,oral bacterial microbiome and fungal microbiome in the development of ALD.We highlight the potential mechanisms by which microbiome dysbiosis contributes to ALD,including short chain fatty acid changes,bile acid metabolism,intestinal barrier function,release of bacterial and fungal products,and inflammation.In addition,we summarize the recent developments targeting the microbiome in prevention and treatment of ALD,including dietary nutrient interference,herbal medicine,antibiotics,anti-fungal agents,probiotics,engineered bacterial therapy,fecal trans-plantation and oral hygiene.Although recent preclinical studies have advanced our understanding of the microbiome and ALD,clinical studies,especially prospective studies with large samples,are needed to better understand the cause-effect of microbiome dysbiosis in ALD.Identifying new precision-based strategies targeting the microbiome are expected to be developed as more effective therapies in ALD.

Objective To explore the impact of intermittent androgen deprivation therapy on prostate volume and lower urinary tract symptoms (LUTS) in patients with prostate cancer combined with prostatic hyperplasia (BPH),and to evaluate the clinical effect of intermittent androgen deprivation therapy as compared with conventional drug in patients with BPH.Methods Patients with prostate cancer (n=57) and BPH (n=83) were respectively treated with intermittent androgen deprivation therapy and finasteride combined with alpha-receptor antagonist.Prostate volume,international prostate symptom score (IPSS),quality of life index (QOL) and maximum urinary flow rate (Qmax) in patients were observed before and 1,3,6 and 12 months after treatment.Results The improvements in prostate volume,IPSS,QOL and Qmax were higher in prostate cancer patients treated with intermittent androgen deprivation therapy than in BPH patients treated with finasteride combined with alpha-receptor antagonist (P ＜ 0.05).Conclusions Intermittent androgen deprivation therapy can significantly reduce prostate volume and improve LUTS in patients with prostate cancer,and has a better clinical effect than finasteride combined with alpha-receptor antagonist treatment.

Objective To evaluate the diagnostic and therapeutic status of lower urinary tract symptoms (LUTS) in the elderly outpatients with benign prostatic hyperplasia (BPH) in Guangzhou.Methods The investigation was conducted in outpatient departments for elderly patients in 3 hospitals of Guangzhou. The eligible male patients with LUTS/BPH were chosen from patients who came to the clinic in the process of investigation. Results The 29.7% (1824/6140) of them had history of LUTS/BPH previously or presently. In 134 patients received medical questionnaire, the proportion of LUTS/BPH patients with mild, middle and severe degree based on international prostate symptom score (IPSS) was 24.5%, 72.5% and 3.0% respectively. The abnormal percentage of PSA was 37. 3 %. The most common examinations that patients received were directeral rectun examination (96.8%), PSA (88. 7%) and transabdominal ultrasonography (84.8%). The 44.7% of cases were given the treatment of 5α-reductase inhibitor, and 24.7% of cases received a combination therapy of 5α-reductase inhibitor plus α receptor blocker. The 16.7% of cases were given a combination treatment of 5α-reductase inhibitor plus herbs. The proportion of therapy with α receptor blocker and herbs was similar (6.8% and 7.1% respectively). Conclusions LUTS/BPH is one of the most common diseases in elderly male patients. The examinations conducted by doctors are unreasonable.The doctors are easy to ignore inquirement of patient's history and IPSS. The drugs conducted by doctors are reasonable basically.

Objective:The purpose of this study was to examine the clinical features and initial treatment outcomes of elderly individuals with idiopathic membranous nephropathy.Methods:This study retrospectively analyzed the clinical characteristics and therapeutic effect of hospitalized patients aged 60 years or older with renal-biopsy-proven idiopathic membranous nephropathy for at least one year.Results:This study enrolled a total of 91 elderly patients with IMN, consisting of 51 males(56.0%)and 40 females(44.0%). The median age of the patients was 67 years.The urinary protein creatinine ratio(uPCR)and urinary albumin creatinine ratio(uACR)of the patients were 4 454.3 mg/g and 2 258.5 mg/g, respectively.The median 24-hour urinary protein and urinary albumin levels were 5 098.2 mg/24 h and 2 800.6 mg/24 h, respectively.The average estimated glomerular filtration rate(eGFR)was(60.5±20.4)ml·min -1·1.73 m -2.Out of the total of 61 patients, 67.0% achieved remission, including complete and partial remission, within a year of renal biopsy.The levels of uPCR and uACR were significantly higher in the non-remission group compared to the remission group(5 462.5 vs.2 271.1 mg/g, P<0.001; 2 774.4 vs.1 320.0 mg/g, P=0.001). Additionally, the levels of 24h urinary protein and urinary albumin were significantly higher in the non-remission group compared to the remission group(6 526.4 vs.3 210.4 mg/g, P=0.002; 3 067.7 vs.2 102.4 mg/g, P=0.007). The remission group had a higher proportion of patients receiving immunosuppressive therapy(85.2% vs.33.3%, P<0.001). The remission rates were higher in patients treated with glucocorticoid combined with cyclophosphamide, glucocorticoid combined with calcineurin inhibitors, or glucocorticoid combined with mycophenolate mofetil compared to those receiving conservative treatment(88.2% vs.31.0%, P=0.001; 80.0% vs.31.0%, P<0.001; 100.0% vs.31.0%, P=0.007). There was no significant difference in remission rate between the three immunosuppressive therapy groups( P>0.05). However, upon further analysis, it was found that the levels of uPCR, uACR, and serum cystatin C(CysC)were higher in the immunosuppressive therapy groups compared to conservative treatment.Additionally, serum total protein and albumin were lower in the immunosuppressive therapy groups, and these differences were statistically significant( P<0.05). Conclusions:The majority of elderly patients diagnosed with IMN have multiple comorbidities.For those at high risk with elevated urinary protein levels, early initiation of immunosuppressive therapy may lead to a higher initial urinary protein remission rate.Therefore, it is advisable to develop individualized treatment plans for elderly patients with IMN based on their clinical characteristics, as well as the risks and benefits associated with immunosuppressive therapy.

Objective: To investigate the number and distribution of dendritic cells (DCs), macrophages and M2 macrophages in renal tissues of patients with IgA nephropathy (IgAN) and their correlation with clinicopathological parameters, and explore its role in the progression of IgAN. Methods: Renal tissue samples from 42 patients aged ≥18 years with IgAN were collected by kidney biopsy in Guangdong Provincial People's Hospital from January 2018 to June 2018. The patients were divided into different groups according to Oxford classification and Lee grade classification criteria. The distribution and number of DCs (CD209), macrophages (CD68) and M2 macrophages (CD68 and CD206) were detected by immunohistochemistry. Spearman correlation test was used to analyze the correlation between the number of DCs and macrophages in renal tissues and clinical pathological parameters. Results: The number of DCs in the glomeruli of the M1, T0 and C1 groups increased significantly compared with the M0, T1 and C0 groups, and the number of DCs in the renal interstitium of the T1 group increased significantly compared with the T0 group (all P<0.05). The number of glomerular macrophages in group C1 was significantly higher than that in group C0. The number of macrophages in S1, T1 and Lee IV-V tubulointerstitial groups was significantly higher than that in S0, T0 and Lee II-III groups (P<0.05). The number of M2 macrophages in the S1, T1 and Lee IV-V groups was significantly higher in the tubulointerstitial group than in the S0, T0 and Lee II-III groups (all P<0.05). The blood urea nitrogen, serum creatinine and 24 h urine protein levels in the T1 and Lee IV-V groups were significantly higher than those in the T0 and Lee II-III groups, and the serum albumin levels in the Lee IV-V group were significantly lower (all P<0.05). Spearman correlation analysis showed that the number of DCs in renal interstitium was positively correlated with the proportion of tubulointerstitial fibrosis. There were a positive correlation between the proportion of glomerular segmental sclerosis and tubulointerstitial fibrosis and renal interstitial macrophages and M2 macrophages. The number of M2 macrophages was positively correlated with serum creatinine and 24 h urine protein (both P<0.05). Conclusions The number of DCs and M2 macrophages in kidneys are positively correlated with the clinicopathological features of IgAN patients, which indicates that they may be associated with disease progression.

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*