To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Interleukin-8 ; Interleukin-10 ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; I-kappa B Kinase ; Spleen ; Irbesartan ; Uridine Triphosphate ; Yang Deficiency/drug therapy* ; Kidney/pathology*

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

AIM To observe the changes of serum ROS,MDA,SOD levels in chronic renal failure (CRF) patients with damp-heat syndrome and to explore the intervention effect of Qingshen Granules (Hedyotis diffusae Herba,Salviae miltiorrhizae Radix et Rhizoma,Artemisiae scopariae Herba,etc.) on oxidative stress.METHODS Seventy cases of CRF patients with damp-heat syndrome were randomly and equally divided into control group and treatment group.Sixty cases completed the study,thirty-one cases in the treatment group,twenty-nine cases in the control group.Twenty other cases served as the normal group.The treatment group and the control group were given the basic treatment of western medicine and retention enema of TCM.The treatment group was added Qingshen Granules for eight weeks.The levels of U-Pro/24 h,Scr,BUN,estimated glomerular filtration rate (eGFR),serum ROS,MDA and SOD were measured before and after the treatment,and were compared with the normal group.RESULTS Both total effective rates on disease and on traditional Chinese medicine syndrome in the treatment group were 83.87％,significantly higher than those in the control group (51.72％ and 48.28％),respectively.The levels of U-Pro/24 h,Scr and BUN were obviously lower in the treatment group after the treatment,and eGFR was obviously higher as compared with those in the control group.Before the treatment,the levels of ROS and MDA in the treatment and control groups were significantly higher than those in the normal group,and the level of SOD was significantly lower;the levels of ROS and MDA were reduced in the treatment group after the treatment,and the level of SOD was increased;these changes in the treatment group were more significant than those in the control group.CONCLUSION Qingshen Granules can ameliorate clinical symptoms in CRF patients with damp-heat syndrome,decrease the levels of U-Pro/24 h,Scr and BUN,increase eGFR level,inhibit oxidative stress,and enhance antioxidant capacity,ultimately delay the development of renal fibrosis.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVETo evaluate the effects of two gastric cancer screening schemes for early detection of gastric cancer in a high-risk population.

METHODSA cluster random sampling method was used to select local residents aged 40-69 years from Linqu County, Shandong Province. "Serum pepsinogen initial screening combined with further endoscopic examination (PG scheme)" and "direct endoscopic examination (endoscopy scheme)" were conducted. The associations between screening schemes and detection rates of gastric cancer, and early gastric cancer/high-grade intraepithelial neoplasia were evaluated by unconditional logistic regression analysis.

RESULTSOverall, 3654 and 2290 participants completed PG and endoscopy schemes, respectively. A total of 11 (0.30%) cases of gastric cancer and 10 (0.27%) cases of high-grade intraepithelial neoplasia were detected by PG scheme, of which 7 (0.19%) cases were early gastric cancer. While, 19 (0.83%) cases of gastric cancer and 10 (0.44%) cases of high-grade intraepithelial neoplasia were detected by endoscopy scheme, with 12 (0.52%) cases of early gastric cancer. Compared with the PG scheme, the endoscopy scheme had a significantly higher detection rates of gastric cancer (OR = 2.83, 95%CI 1.34-5.98), and early gastric cancer/high-grade intraepithelial neoplasia (OR = 2.12, 95%CI 1.12-4.02).

CONCLUSIONSThe endoscopy scheme is more effective in the detection of gastric cancer in a high-risk population, particularly for early gastric cancer/high-grade intraepithelial neoplasia than the PG scheme.

Adult ; Aged ; Carcinoma ; blood ; diagnosis ; Carcinoma in Situ ; blood ; diagnosis ; Early Detection of Cancer ; methods ; Female ; Gastroscopy ; Humans ; Male ; Mass Screening ; methods ; Middle Aged ; Pepsinogen A ; blood ; Stomach Neoplasms ; blood ; diagnosis

Objective To explore the value of hippocampus hydrogen proton magnetic resonance spectrum analyzes (1 H-MRS) for the diagnosis of temporal lobe epilepsy (TLE) in children.Methods Singa HDe GE company to attain the 1.5T magnetic resonance imaging apparatus was used to analyze the conditions of 30 cases of children with TLE and the other 30 healthy controls received brain MRI and 1H-MRS check.The hippocampal N acetyl aspartate (NAA),creatine (Cr),and the choline (Cho) concentration were observed; NAA/(Cho + Cr),the ratio of NAA/Cr and NAA/Cho were analyzed.The analysis of biochemical components in the hippocampus was performed on the affected sides and the healthy sides of TLE group and the sides of the healthy control group,respectively.Results Hippocampus were anormal by combining MRI and MRS in 28 cases.Levels of NAA/(Cho + Cr),NAA/Cho,and NAA/Cr in the trouble sides of the TLE group had the remarkable statistical significance compared with the normal sides,and the healthy control group (all P ＜ 0.05),but there was no remarkable statistic significance between the normal sides and the healthy control group (all P ＞ 0.05).Nineteen cases had been confirmed by surgery,and postoperative pathological changes:brain surface were wavy,cortex were uneven;there were giant neurons,immature neurons,and scattered across the deformity of neurons in the cortex.A small amount of ectopic neurons can be seen in white matter.Conclusions In the TLE children,the reduction of NAA/(Cho + Cr) value of the side hippocampus may help diagnose the hipppcampal sclerosis earlier,and can provide significant evidence for the diagnosis and treatment of TLE in children.

The present study aimed to investigate the effects of ursolic acid on the chloride channels and cell volume in nasopharyngeal carcinoma cells (CNE-2Z). The whole-cell patch clamp technique was used to detect the current, and cell imaging technique was applied to measure cell volume. The properties of the currents induced by ursolic acid were investigated by changing the extracellular osmotic pressure, replacing the extracellular anions and applying chloride channel blockers. The results showed that, under isotonic conditions, the background current was weak and stable. When perfusing the cells with ursolic acid (100 nmol/L), a large current (-59.86 pA/pF ± 4.86 pA/pF at -80 mV, 78.92 pA/pF ± 6.39 pA/pF at +80 mV) was induced. The chloride current showed outward rectification and negligible time- and voltage-dependent inactivation. The reversal potential (-4.83 mV ± 0.30 mV) of the current was close to the calculated equilibrium potential for Cl⁻ (-0.9 mV). The permeabilities of the channel to different anions were ranked in order as follows: Cl⁻ = I⁻ > Br⁻ > gluconate. Hypertonic solutions inhibited the current induced by ursolic acid. The chloride channel blockers, tamoxifen (20 μmol/L) and 5-nitro-2-(3-phenylpro-pylamino) benzoic acid (NPPB, 100 μmol/L), suppressed the current. Furthermore, ursolic acid decreased the cell volume by (11.78 ± 1.20)% in 1 h, and the effect was inhibited by NPPB. These results suggest that ursolic acid can activate chloride channels, resulting in outflow of Cl⁻ and decrease of cell volume in nasopharyngeal carcinoma cells.
Carcinoma ; Cell Differentiation ; Cell Line, Tumor ; Cell Size ; Chloride Channels ; antagonists & inhibitors ; metabolism ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; Patch-Clamp Techniques ; Tamoxifen ; pharmacology ; Triterpenes ; pharmacology

BACKGROUNDMounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133(+) cancer stem cells.

METHODSThe response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133, and the CD133(+) subset of cells was separated and analyzed in colony formation assays, cell invasion assays, chemotherapy resistance studies, and analyzed for the expression of the drug resistance gene ABCG2.

RESULTSAbout 1% - 2% of Hep-2 cells were CD133(+) cells, and the CD133(+) proportion was enriched by chemotherapy. CD133(+) cancer stem cells exhibited higher potential for clonogenicity and invasion, and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2.

CONCLUSIONSThis study suggested that CD133(+) cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133(+) cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.

AC133 Antigen ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; Antigens, CD ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Blotting, Western ; Carcinoma ; genetics ; metabolism ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Flow Cytometry ; Fluorouracil ; pharmacology ; Glycoproteins ; genetics ; metabolism ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Neoplastic Stem Cells ; cytology ; drug effects ; metabolism ; Paclitaxel ; pharmacology ; Peptides ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

Objective To compare the stresses on the end plate of adjacent lumbar vertebrae between intra-segmental fixation and inter-segmental fixation in treating lumbar spondylolysis by three-dimensional finite element analysis. Method Based on the established finite element model of L4 lumbar spondylolysis, the lumbar internal fixation such as rods and trans-pedicle screws were reconstructed to make the finite element models of intra segmental and inter segmental internal fixation with the same constraint and loading conditions. The stresses on endplate of adjacent lumbar vertebrae of finite element models were measured under three mechanical conditions:spondylolysis, intra-segmental fixation and inter-segmental fixation. Results High stresses were observed under two kinds of internal fixation conditions compared with the spondylolysis condition at the lower endplate of L4 under axial loading(P<0.05). The stresses at the lower endplate of L4 under intra segmental fixation condition were similar as that of the spondylolysis condition under flexion, extension and lateral bending loading. With the same loading, higher stresses were observed under inter-segmental fixation condition compared with the spondylolysis condition, and so did the lower stresses at upper endplate of S1(P<0.05). The lower stresses at the upper endplate of S1 under intra-segmental fixation condition were observed compared with the other two conditions under rotating loading (P<0.05). Conclusions The intra segmental fixation can not only provide stability for lumbar spondylolysis under axial, flexion, extension, lateral bending,but also preserve the normal activity at adjacent disc levels, especially under rotating loading.

OBJECTIVETo compare the biomechanical performances of different wires and cable fixation devices in posterior instrumentation for atlantoaxial instability, and test the effect of different fixation strengths and fixation approaches on the surgical outcomes.

METHODSSix specimens of the atlantoaxial complex (C0-C3) were used to establish models of the normal complex, unstable complex (type II odontoid fracture) and fixed complex. On the wd-5 mechanical testing machine, the parameters including the strength and rigidity of anti-rotation, change and strength of stress, and stability were measured for the normal complex, atlantoaxial instability complex, the new type titanium cable fixation system, Atlas titanium cable, Songer titanium cable, and stainless wire.

RESULTSThe strength and rigidity of anti-rotation, change and strength of stress, stability of flexion, extension and lateral bending of the unstable atlantoaxial complex fixed by the new double locking titanium cable fixation system were superior to those of the Songer or Atlas titanium cable (P<0.05) and medical stainless wire (P<0.05). Simultaneous cable fastening on both sides resulted in better fixation effect than successive cable fastening (P<0.05). Better fixation effect was achieved by fastening the specimen following a rest (P<0.05).

CONCLUSIONSThe fixation effects can be enhanced by increased fastening strengths. The new type double locking titanium cable fixation system has better biomechanical performance than the conventional Songer and Atlas titanium cables. Fastening the unstable specimens after a rest following simultaneous fastening of the specimen on both sides produces better fixation effect.

Atlanto-Axial Joint ; physiopathology ; surgery ; Biomechanical Phenomena ; Bone Wires ; Cadaver ; Humans ; Internal Fixators ; Joint Instability ; physiopathology ; surgery ; Orthopedic Fixation Devices