Objective To evaluate the value of intrathecal synthetic related markers in patients with mild cognitive impairment(MCI),Alzheimer's disease(AD),and other types of dementia.Methods Retrospec-tively collect the clinical data of 577 patients diagnosed with MCI(MCI group,178 cases),AD(AD group,131 cases),and other types of dementia(other types group,268 cases)from June 2019 to July 2023 in Beijing Tiantan Hospital,Capital Medical University.Oligoclonal zone electrophoresis(OCB)and 24 h intrathecal pro-tein synthesis rate(ISR)of each group were investigated,and the difference of different indexes among the groups was compared to evaluate the value of related indexes in the differential diagnosis of different diseases.Results Compared with AD group and other groups,AD group had a higher proportion of females,more patients were＞50-70 years old,and the incidence of abnormal lipid metabolism was higher,with statistical significance(P＜0.05).There were significant differences in OB(S),cerebrospinal fluid albumin,serum albumin and cerebrospinal flu-id IgG in different disease groups(P＜0.05).IgG index and ISR in patients with positive SOB(CSF)were higher than those in negative and weakly positive patients,and the differences were statistically significant(P＜0.001).IgG index was positively correlated with ISR(r=0.878,P＜0.001).Conclusion Intrathecal synthetic mark-ers such as IgG index,SOB(CSF)and 24 h ISR have synergistic effects in the diagnosis of cognitive dysfunction and various dementias,which can be collectively utilized in the diagnosis of diseases.

Objective:To discuss the effect of NOD-like receptor protein 3(NLRP3)inflammasome on the renal interstitial fibrosis in the unilateral ureteral obstruction(UUO)model rats,and to clarify its potential mechanism.Methods:Thirty healthy male Wistar rats were randomly divided into sham operation group(n=6)and UUO group(n=24).The rats in sham operation group underwent the dissection of the ureter without ligation,while the rats in UUO group were sacrificed on the 3rd,7th,and 14th days after operation,and based on the treatment duration,the rats were divided into UUO 3 d group(n=8),UUO 7 d group(n=8),and UUO 14 d group(n=8).HE staining and Masson staining were used to observe the pathomorphology of kidney tissue of the rats in various groups;reagent kits were used to detect the levels of malondialdehyde(MDA),activities of superoxide dismutase(SOD),and levels of hydroxyproline(HYP)in kidney tissue of the rats in various groups;immunohistochemistry method was used to detect the expression levels of α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)proteins in kidney tissue of the rats in various groups;Western blotting method was used to detect the expression levels of NLRP3 protein in kidney tissue of the rats in various groups.Results:The HE staining results showed significant tubular dilation,interstitial edema,and widening,with increased infiltration of inflammatory cells,and shedding of epithelial cells was seen in parts of the tubular lumina of the rats in UUO group.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);compared with UUO 3 d group and UUO 7 d group,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).The Masson staining results showed that in UUO group,there was evident infiltration of inflammatory cells in the renal interstitium and a noticeable increase in fibrotic tissue proliferation;with the increasing of duration of UUO,some tubular structures disappeared,and the interstitial widened further with gradually increasing collagen deposition,particularly at the corticomedullary junction.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);and compared with UUO 3 d and UUO 7 d groups,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).Compared with sham operation group,the levels of MDA in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05),and the SOD activities were significantly decreased(P<0.05).Compared with sham operation group,the levels of HYP in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the level of HYP in obstructed kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05).The immunohistochemistry results showed that compared with sham operation group,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significant increased(P<0.05);compared with UUO 3 d and UUO 7 d groups,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05);compared with sham operation group,the expression levels of TGF-β1 protein in renal tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the expression levels of TGF-β1 protein in the tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 14 d group were significantly decreased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of NLRP3 protein in kidney tissue of the rats in UUO 7 d and UUO 14 d groups were significantly increased(P<0.05).Conclusion:The NLRP3 inflammasome plays a critical role in renal fibrosis of the UUO rats,and its mechanism may be related to the increasing of oxidative stress and the increasing of expression level of TGF-β1 protein.

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.

Objective:To analyze the diagnosis and treatment process of a kala-azar case with prominent renal damage treated with liposomal amphotericin B (L-AmB), and to provide theoretical basis for clinical diagnosis and treatment.Methods:A retrospective analysis method was used to analyze the clinical data, diagnosis and treatment process and laboratory test results of a case of kala-azar with prominent renal damage who presented to the Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University on June 30, 2020.Results:A 56-year-old female patient presented with fever (the highest body temperature was 38.2 ℃) and chills. The results of clinical laboratory tests showed that hemoglobin(55 g/L), red blood cell (2.68 × 10 12/L), white blood cell (1.06 × 10 9/L) and platelet count (8.00 × 10 9/L) were decreased, renal function showed abnormal blood urea nitrogen and creatinine, spleen enlargement, etc., and the diagnosis of kala-azar combined with kidney insufficiency was confirmed by blood and bone marrow Leishmania spp. examination. With the assistance of continuous renal replacement therapy (CRRT), after a small dose of L-AmB was initially and slowly increased and maintained at a low dose, the patient's body temperature was normal, the blood routine showed that the three-lineage cells gradually increased, and the renal function showed blood urea nitrogen and creatinine decreased gradually the spleen was retracted; no recurrence was found at follow-up after 6 months, and renal function returned to normal. Conclusions:L-AmB is safe and effective in the treatment of kala-azar with renal damage as the prominent manifestation. The patient is not only cured by etiology, but is also recovered renal function.

Objective To evaluate the effect of high-frequency chest well oscillation expectoration system on ventilator-associated pneumonia (VAP) and time for withdrawing mechanical ventilation (MV) system in ICU patients with invasive mechanical ventilation (IMV). Methods 100 ICU patients with IMV were divided into observationgroup (n = 50) and control group (n = 50). The high-frequency chest well oscillation expectoration was used in the former group and the mechanical vibration expectoration was used in the latter. The two groups were compared in terms of amount of sputum, vital signs (heart rate, breathing, systolic blood pressure and blood oxygen saturation), time for withdrawing MV system and VAP rate. Results On days 1, 2, 3, 4 and 5, the amount of sputum in the observationgroup was (33.5 ± 4.2)mL/d, (41.1 ± 3.0)mL/d, (38.2± 3 .5) mL/d, (34.8 ± 2.5) mL/d and (31.1 ± 2.1) mL/d, and those of the control group respectively was (27.4 ± 3.1) mL/d, (30.3 ± 3.6) mL/d, (28.1 ± 2.2) mL/d, (25.7±1.8)mL/d and (20.8 ± 1.7)mL/d. The differences between the two groups were statistically significant (P < 0.05). After sputum expectoration, the blood oxygen saturation of the observationgroup was significantly higher than the control group [(97.5 ± 0.9) vs. (95.2 ± 1.0)] (P <0.05), but there were no statistical differences in heart rate, breathing and systolic blood pressure (P > 0.05). The time for withdrawing MV system in the observationgroup and the control group respectively was (5.8 ± 2.2)d and (9.5 ± 1.8)d, (P < 0.05). The rates of VAP in the observationgroup and the control group respectively was 30.0% (15/50) and 52.0% (26/50), with significant difference between them (P < 0.05). Conclusion The high-frequency chest well oscillation expectoration for ICU patients with invasive mechanical ventilation can promote sputum expectoration , improve blood oxygen saturation , shorten the time for withdrawing the ventilator, and prevent the incidence of VAP.

BACKGROUND: p38 mitogen-activated protein kinase signal transduction pathway is a member of the mitogen-activated protein kinase family. It plays an important role in the development of osteoarthritis. OBJECTIVE: To review the progress of p38 mitogen-activated protein kinase signal transduction pathway in the pathological process of osteoarthritis. METHODS: An online search of CNKI and PubMed databases was performed for articles using keywords of “p38 mitogen-activated protein kinase signal transduction pathway, osteoarthritis, articular cartilage, chondrocyte” in Chinese and English, respectively. Relevant articles were summarized from three aspects of introduction of p38 signal transduction pathway, the role of p38 mitogen-activated protein kinase signal transduction pathway in osteoarthritis and the inhibitor of p38 in osteoarthritis. A total of 90 articles were included. According to inclusion criteria, a number of 46 articles were retained at last. RESULES AND CONCLUSION: p38 mitogen-activated protein kinase signal transduction pathway has a close relation with chondrocyte hypertrophy and calcification, chondrocyte apoptosis, synthesis of cartilage matrix metal oproteinase, production of proinflammatory cytokines, and exerts a significant effect on the development of osteoarthritis. p38 mitogen-activated protein kinase is involved in the formation and development of osteoarthritis through a variety of complex mechanisms and plays a very important role. Therefore, blocking p38 mitogen-activated protein kinase signaling pathway may be a new target in the treatment of osteoarthritis.

Objective To investigate the association of radial arterial calcification damage with bone mineral density (BMD) and bone metabolism biomarkers in uremia patients.Methods Sixty-seven incident hemodialysis patients were recruited into uremic group.Serum creatinine,calcium,phosphorus,lumbar spine and femoral neck BMD were measured.Parathyroid hormone (iPTH),25OHD,1,25(OH)2D,fibroblast growth factor (FGF) 23,bone specific alkaline phosphates (BAP) and osteocalcin (BGP),type Ⅰ collagen pyridine crosslinked C-telopcptidc (ICTP) were detected.Radial artery calcification was analyzed by von Kossa staining and transmission electron microscopy.Arterial type Ⅰ collagen (Col Ⅰ) expression was examined.Twenty-three healthy cases received serum and BMD examination only as control.Results Uremic patients presented higher serum phosphate,iPTH,FGF23,lower serum calcium,25OHD,1,25 (OH)2D (all P ＜ 0.05),and lower lumbar spine and femoral neck BMD (all P ＜ 0.01) compared to controls.Significant calcium deposit was observed in radial arteries in 24 uremic cases (35.8％),including 10 cases of diabetes.Immunohistochemistric assay confirmed that Col Ⅰ expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers.No correlation was showed between iPTH and radial artery calcification (r =-0.08,P =0.306),but after stratified by iPTH levels,correlation of iPTH and calcification was found in low iPTH (＜ 150 ng/L) group and high iPTH group (＞ 300 ng/L) (r =-0.41,0.31,P=0.044,0.023).Diabetes,lumbar spine and femoral neck BMD,ICTP,FGF23 were correlated with arterial calcification (r =0.62,-0.25,-0.43,0.34,0.86,P =0.000,0.001,0.012,0.018,0.000).Multiple regression analysis showed femoral neck BMD,ICTP,FGF23 levels were independently associated with radial arterial calcification (β =-0.221,0.181,0.260,P =0.021,0.024,0.036).Conclusion In uremic patients,reduced BMD,abnormal bone turnover rate,especially accelerated bone reabsorption,and increased serum FGF23 level are independently associated with radial artery calcification.

Objective To investigate the expression of inflammatory mediators in renal tubular epithelial cells in patients with diabetic nephropathy (DN) and to explore the possible clinicopathological significance. Methods Twenty-three patients with DN diagnosed by renal biopsy and 10 patients with renal cell carcinoma undergone nephrectomy were allocated into DN group and control group, respectively. The renal expression of NF-κB p50, NF-κB p65, NF-κB p65 mRNA, MCP-1, OPN, α-SMA, and FN was detected by immunohistochemical or in situ hybridization assay. Serum creatinine, urinary N-acetylglucosaminedase (NAG), urinary albumin and 24-hour urinary protein were detected. The correlation between these inflmmnatory markers and clinicopathological data were analyzed. Results (1)Among all the 23 DN patients, granular degeneration of the renal tubular epithelium, focal tubular atrophy, infiltration of inflammatory cells and interstitial fibrosis were apparent, and none of these were found in control group. (2) Immunohistochemical and in situ hybridization assay showed that, compared with control group, expression of these factors increased significantly in renal tubular cells or interstitium in DN patients, and expression of α-SMA or FN was not found in tubular epithelial cells. (3)Statistics assay showed the tubular NF-κB p65 protein expression was correlated with all of the following factors: NF-κB p50 protein (r=0.792) and NF-κB p65 mRNA (r=0.763), tubular MCP-1 (r=0.825) and OPN (r=0.869) expression, interstitial α-SMA (r=0.327) and FN (r=0.432) expression, proteinuria(r=0.710), estimated glomerular filtration rate (eGFR) (r=-0.728), and urinary NAG (r= 0.930), P<0.01 respectively. Conclusion Tubular inflammation may play a role in the pathogenesis and progression of DN.

Objective To examine the changes of histological parameters of radial artery in uremia,and to explore their effects on arterial stiffness.Methods Sixty uremic patients underwent arteriovenous fistula surgery for hemodialysis and 20 healthy subjects received healthy examination were collected as uremia group and control group, respectively.Segments of radial arteries were obtained from all of uremic subjects and were evaluated by HE, Masson, van Kossa staining and electron microscopy.The expressions of osteopontin (OPN), α-SMA and elastin in arterial wall were detected by immunostaining, and apoptotic cells were determined by TUNEL assay.All of the subjects in the two groups received brachial ankle pulse wave velocity (baPWV) examination and the results were compared.The associations among histological parameters and baPWV were analyzed.Results More than one half (34/60) of artery samples presented uniformly thickening intima, in which most of cells expressed α-SMA and a few cells underwent apoptosis.The subendothelial matrix was abundant in collagen fibers, and no calcium deposition was found.The media thickened obviously, with increased collagen fibers, reduced elastin, unchanged α-SMA expression, and a few apoptotic smooth muscle cells.Two thirds uremic arteries expressed OPN, of which only one half had significant calcium deposition.The adventitia thickened and no calcium deposition was found.The baPWV level in uremic subjects was ( 18.5 ± 3.2 ) m/s, far greater than that in control subjects ( P ＜ 0.001 ).Statistical analysis showed that baPWV value was correlated with media thickness, calcification degree, and collagen content positively, and with elastin expression negatively.For diabetic uremic subjects, the OR values of vascular calcium deposition and remarkably-elevated baPWV value were 3.1, 2.3, respectively.Conclusions Radial arterial intima often presents hyperplasia which is not related with baPWV increment in uremia.Arterial media calcification and collagen content incremental are the most two protuberant characteristics in uremia, especially in ones accompanied with diabetes.Medical calcification, collagen accumulation, and e]astin reduction may contribute to the increased arterial stiffness in uremia.

Objective To investigate the clinical application of MR hydrography (MRH) in diagnosing alveolar echinococcosis (AE). Methods Thirty-four patients with suspected alveolar echinococcosis were examined using MRH in addition to conventional magnetic resonance imaging(cMRI).Thirty-two of the 34 patinets had surgery and the pathological diagnoses were alveolar echinococcosis.Results Among 128 lesions in these 32 patients found at surgery,cMRI examination found 68 lesions and MRH found 108 lesions.The sensitivity of cMRI examination was (53.13 ±0.04) %,the specificity was (92.59 ± 0.05) %,concordance rate was (60.00 ± 0.03) %.The sensitivity of MRH examination was (84.38 ± 0.03) %,the specificity was (81.48 ± 0.08) %,concordance rate was (83.87 ± 0.03) %.Comparing concordance rate of cMRI examination and MRH,significant difference was found (U = 5.44,P < 0.01).Conclusion MRH technique can raise the sensitivity and concordance rote for diagnosing AE. This technique should be employed in the evaluation of patients suspected of AE.