ObjectiveTo find out if the immune system derived thyroid stimulating hormone(TSH) β splice variant(TSHβ-Ⅴ) would be regulated by circulating thyroid hormone levels to get a further understanding of the function and mechanism of this TSHβ-Ⅴ in thyroid homeostasis.MethodsA total of 20 weaning Balb/c mice (half male and half female) were selected and randomly divided into two groups according to their body mass and gender(n =10).Mice of control group were fed with common diet and deionized water.Mice of the low-iodine(LI) group were fed with low-iodine diet(containing iodine 20 - 40 μg/kg,iodine-intake about 0.25 μg/d) and deionized water.The experimental period was 3 months.At the end of the experiment,mice were executed and the blood was collected to observe the levels of TSH and thyroid hormone by chemiluminescence immunoassay (CIA) ; bone marrow (BM),peripheral blood(PBL),thyroid gland and pituitary were collected to assay the TSHβ-Ⅴ mRNA expression by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR).ResultsThe serum free thyroxine(FT4) and total thyroxine(TT4) levels in LI group of mice[(0.47 ± 0.70)nmol/L,(2.41 ± 0.28)pmol/L] were significantly lower than that of the control group of mice [(55.2 ± 3.68) nmol/L, (32.72 ± 1.02) pmol/L,t =43.81,86.04 、all P ＜ 0.01 ] and the serum total triiodothyronine(TT3) and free triiodothyronine(FT3) reduction in LI group of mice[ (0.76 ± 0.08)nmol/L,(4.01 ± 0.40)pmol/L] were significantly lower than that of the control group of mice [ (1.10 ± 0.06)nmol/L,(5.40 ± 0.38)pmol/L,t =9.81,7.5 1,P ＜ 0.01 ].Iodine insufficiency strongly elevated the serum TSH in LI group of mice[ (35.67 ± 17.39)mU/L] than that in control group of mice[ (0.24 ± 0.10)mU/L,t =- 6.11,P ＜ 0.01 ].The mRNA levels of TSH β-Ⅴ in BM (9.62 ± 0.60) and in PBL( 9.25 ± 0.83 ) of LI group of mice were lower than those in control group of mice (7.69 ± 0.36,7.11 ± 0.41,t =6.77,5.64,P ＜ 0.01),while the mRNA level of TSH β-Ⅴ in pituitary of LI group of mice (1.99 ± 0.61) was increased compared with that in control group of mice (5.75 ± 0.98,t =- 8.02,P＜ 0.01).Compared with control group of mice(9.12 ± 0.62),the level of thyroid TSH β-Ⅴ mRNA in LI group of mice (9.32 ± 0.91 ) was not significantly changed (t =0.45,P ＞ 0.05).There was no detectable native TSHβ in BM,PBL and thyroid.The mRNA level of native TSHβ in pituitary in LI group of mice( - 7.17 ± 1.78) was dramatically elevated compared to that in control group of mice( - 1.43 ± 0.51,t =- 7.60,P ＜ 0.01 ).ConclusionsThe mRNA levels of TSHβ-Ⅴ are suppressed in BM and PBL in low iodinediet induced hypothyroidism mice,which suggest that immune system derived TSHβ-Ⅴ may be more important thannative TSHβ in immune-thyroid regulation.

OBJECTIVETo summarize the Patho-typing and the clinical manifestation of biliary cast syndrome (BCS) in patients after orthotopic liver transplantation.

METHODSThe clinical manifestation, findings,therapeutic means and efficacy of 103 patients with biliary cast syndrome after orthotopic liver transplantation were retrospectively analyzed. According to the injury level of biliary duct epithelium, patients were divided into different groups. All cases were followed up for twelve months. The place, degree and time after operation would be recorded when non-anastomotic biliary stricture was found.

RESULTSThere were 59 BCS cases in the general hospital of armed police force of China. The incidence rate of BCS was 9.1%. Many BCS patients showed symptoms such as jaundice, deep urine color, gray stools, itch of skin and fever. Some were asymptomatic. In laboratory test, the liver functional enzyme in serum were increased, the total white cell count in peripheral blood was increased either. Cholangiography via T tube of biliary tract might show filling defect. According to the change degree of the biliary tract tree, there were four types filling defect concluded from all the presentation in BCS patients. Solid obturation of biliary tract were found by the check with optical fiber choledochoscope in all BCS patients, necrosis of biliary tract epithelium were observed in partial BCS patients. According to the injury level of biliary duct epithelium (gradually aggravated), BCS patients were divided into six groups (type I, type II, type III, type IV, type V and type VI). Fourteen cases were found in type I and 18 in type II. No clinical symptom was found in these two groups, a few indicators in serum (alanine aminotransferase ALT, total bilirubin TBIL, direct bilirubin DBIL) were in normal range, and others (gamma-glutamyl transferase GGT, alkaline phosphatase ALP) were heightened in 5 patients. There was no biliary cast (BC) found anymore in the period of follow-up in two groups. No stricture was found in both group. Twenty-seven cases in type III and 23 cases in type IV, it was found there were about 33.4% patients accompanied with fever and 25.9% accompanied with jaundice in type III. Paralleled,there were about 30.4% and 34.8% patients in type IV. The liver functional enzyme in serum were found increased in both type. After supporting treatment for 3-6 months,there were 5 and 3 patients present as mild non-anastomotic biliary stricture in type III and type IV group. In the group type V, there were 13 patients. The detected liver functional indicators in serum were increased. After supporting treatment for 6-12 months,there were 4 patients present as moderate non-anastomotic biliary stricture in this group. There were 18 patients in type VI group, all indicators of the liver functional enzyme in serum before the treatment were elevated conspicuously. All patients in this group were found serious stricture up to three places that have not been sustained in the period of follow-up. Nine died of MOSF, 1 died of AOSC, 8 had undergone retransplantation. In the retransplantation patients, 4 died of post operation MOSF, 3 recovered to normal, 1 patient was found BCS once more 15 d after the retransplantation and the third-transplantation was performed 7 months after the second transplantation, no BCS was found again. The deaths total rate was 13.6%, death rate of retransplantation was 44.0%, total cure rate was 54.0%, total improvement rate was 71.0% and total stenosis rate was 29.0%.

CONCLUSIONS(1) According to the check with optical fiber choledochoscope, there are 6 types of patho-typing in BCS patients. The clinical manifestation includes jaundice and fever. The filling defect of the biliary tract tree might showed 4 appearances. (2)The patho-typing contributes to the clinical manifestation and the filling defect of the biliary tract tree.

Adult ; Aged ; Biliary Tract Diseases ; etiology ; pathology ; therapy ; Female ; Follow-Up Studies ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Postoperative Complications ; etiology ; pathology ; therapy ; Prognosis ; Retrospective Studies

Objective To observe the effect of iodine excess(HI),polyinosinic-polycytidylic acid[Poly(I:C),Poly]and thyroglobulin(TG)on the thyroid of mice by the expression of Toll-like receptor 3(TLR3)to reveal the functional role of TLR3 in autoimmune thyroiditis.Methods Forty-two non-obese diabetic mice,body weight (20±3)g,were divided into six groups:control group,HI group,Poly group,TG group,HI+TG group,HI+Poly group. Fed with deionized water and injected intraperitoneally with physiological saline 0.1 ml each day for a week, the mice in control group were injected with physiological saline every other day at the same dose for 1 week before they were sacrificed; HI group drank 0.05% NaI water and were injected intraperitoneally with physiological saline same as control group; Poly group drank deionized water and were injected intraperitoneally with poly 0.1 ml (1 g/L)each day of the week, then the mice were injected with Poly every other day at the same dose for 1 week before they were sacrificed; TG group drank deionized water and were injected intraperitoneally with physiological saline same as control group, immunized with 0.1 mg TG by subcutaneously injecting and the immunization was enhanced after they were fed half dose for 4 and 8 weeks separately. In HI + Poly group, the treatment was the same as HI group and Poly group; HI + TG group: the treatment was the same as HI group and TG group. Eight weeks later, mice were sacrificed and thyroids were taken to make frozen sections, Hematoxylin-Eosin (HE) staining was employed to observe the morphological change of the thyroids. The expression of TLR3 of thyroids was observed under fluorescence microscope after Immumofluorescence using TLR3 antibody and TR3-positive cells were analyzed in the thyroid density. Results HE staining showed thyroids of Poly group had no inflammation under microscope.There were different degrees of inflammatory cell infiltration in HI group and TG group. The inflammatory cell infiltration and the damage of follicular thyroid of HI + TG group and HI + Poly group were serious, and the degrees of inflammation were higher over "++". Thyroid follicular epithelial cell with TLR3 expression could be seen in Poly group and HI group, meanwhile, there were TLR3 strong positive inflammatory cells in HI group under fluorescent microscope. Using stereological analysis of TLR3-positive cell density in the thyroid, the difference between groups was statistically significant(F=7.870, P<0.01 ). TLR3-positive cell density in the thyroid of HI + Poly group was higher[ (9.287 ± 0.522)mm2] than control group[ (0.062 ± 0.025)mm2, P < 0.01] significantly, meanwhile, the density in HI + Poly group was higher than HI group [ (2.574 ± 0.257 )mm2] and Poly group[ (1.361 ± 0.148 )mm2, all P < 0.01]. The density in HI + TG group[ (4.843±0.405)mm2] was higher than HI group and TG group[(1.601 ±0.268)mm2, all P < 0.01 )]. Conclusions Excessive iodine and thyroglobulin can induce thyroiditis, and stimulate the expression of TLR3 in the thyroid follicular epithelial, Poly aggravated thyroiditis induced by iodine excess in NOD mice; TLR3 positive inflammatory cells also appeared in inflammatory region, suggesting that TLR3 is involved in the pathogenesis of autoimmune thyroiditis

OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog (PTEN) and metadherin (MTDH). METHODS Guizhi Fuling Wan (GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition, Wistar rats were given GFW viagavage at 4 g·kg-1·d-1,8 g·kg-1·d-1,16 g·kg-1·d-1,or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera, medium-dose sear, high-dose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells. Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells. RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera. RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli-taxel, the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold, respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec-tively; there was a significant difference between the groups (P<0.01). RT-qPCR results showed that, compared with the blank serum, the sera can up-regulate the expression of PTEN mRNA and down-regulate the expression of MTDH mRNA in a dose-dependent manner. Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement. CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH, up-regulation of PTEN and induction of apoptosis, providing with an experiment basis for the applica-tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.

OBJECTIVETo determine the differentially expressed serum proteins in patients with hepatoma carcinoma and identify a putative diagnostic marker.

METHODThe isobaric tags for relative and absolute quantitation (iTRAQ) labeling method and LC-MALDI-TOF/TOF MS detection method were used to quantify serum proteins in hepatocellular carcinoma patients (n =20) and healthy individuals (n =20). Real-time reverse transcription-polymerase chain reaction was used to verify the differentially expressed proteins by analyzing the corresponding mRNA expression levels in the hepatic carcinoma and healthy hepatocyte samples, as well as in 30 pairs of patient-matched hepatic carcinoma and adjacent normal tissue samples. Western blot analysis was used to verify the protein expression in hepatic carcinoma cells.

RESULTFifty-one proteins were significantly differentially expressed between the hepatic carcinoma group and healthy controls. The iTRAQ protein profile showed that the serum level of clusterin was significantly lower in hepatoma carcinoma patients. The mRNA level of clusterin was 20-fold lower in hepatic carcinoma cells than in healthy hepatocytes, and was 2.38-fold lower in hepatoma tissues than that in adjacent normal tissues. The clusterin protein levels were significantly lower in hepatic carcinoma cells (8.06 vs normal hepatocytes: 27.81; P less than 0.01).

CONCLUSIONThe serum expression of clusterin is significantly decreased in both serum and tissues of hepatic carcinoma patients. The relationship between hepatic carcinoma and clusterin should be evaluated in future studies.

Biomarkers ; Carcinoma, Hepatocellular ; metabolism ; Case-Control Studies ; Clusterin ; blood ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; Mass Spectrometry ; RNA, Messenger ; genetics ; Tumor Cells, Cultured

OBJECTIVETo investigate the ability of Fuzhenghuayu capsule to improve markers of liver fibrosis when provided as supplemental therapy in patients with chronic hepatitis B (CHB) who achieved complete virological response but unsatisfactory resolution of fibrosis markers with nucleos(t)ide analog (NAs) monotherapy.

METHODSOne-hundred-and-ten patients with CHB-related liver fibrosis who had received NA for more than or equal to 2 years and achieved sustained virological response (SVR) but no improvement in liver fibrosis index were randomly divided into two equal groups: experimental group, continued oral NAs (one tablet, 1 time/day) with simultaneous Fuzhenghuayu capsule (1.5 g, 3 times/day) for 48 weeks; control group, continued oral NAs only for 48 weeks. Serum fibrosis markers (hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III procollagen (PIIIP) and IV collagen (IV-C)), liver fibrosis stages, B ultrasonic wave, and liver function were observed before (baseline) and after treatment and compared by statistical analysis.

RESULTSThe baseline levels of fibrosis markers were not significantly different between the experimental and control groups. After treatment, the levels of all of the fibrosis markers were lower in the experimental group (P less than 0.05 vs. control group; HA t = 19.548, LN t = 2.264, PIIIP t = 2.230, and IV-C t = 6.649) and lower than the baseline levels (P less than 0.01; HA t = 12.458, LN t = 7.402, PIIIP t = 4.620, IV-C t = 8.937). The control group also showed a significant reduction in HA and LN levels after treatment (P less than 0.01 vs. baseline; t = 5.202 and 3.444), but PIIIP and IV-C were unaffected. The baseline liver fibrosis stages were not significantly different between the experimental and control groups. After treatment, only the experimental group showed significant improvement in liver fibrosis stages (P less than 0.01). The rates of excellent therapeutic outcome, effectiveness, and non-effectiveness were significantly different between the experimental group (11.3%, 43.4%, and 45.3%) and the control group (1.0%, 22.2%, and 75.6%) (x2 = 9.408, P less than 0.01). Similar trends were observed for improvements in B ultrasonic wave for liver and spleen and in markers of liver function. Finally, neither treatment group experienced adverse effects.

CONCLUSIONFor CHB patients who achieve SVR by antiviral treatment with NAs, but unsatifactory improvement in liver fibrosis indices, administration of supplemental Fuzhenghuayu capsule with continued NAs therapy may represent a safe and effective treatment.

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver ; pathology ; Liver Cirrhosis ; drug therapy ; metabolism ; Male ; Middle Aged ; Nucleotides ; therapeutic use ; Phytotherapy ; Prospective Studies ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of hepatitis B immunoglobulin (HBIG) by different medicating ways in patients with liver transplantation and to explore the methods for calculating the intravenous loading dosage of HBIG.

METHODSThe patients enrolled were randomized into three groups (i.v group, i.m group and domino group). Under the combined utilization with Lamivudine, HBIG was given in different ways during anhepatic phase and the postoperative six days. The physical examination was done, the serum conversion rate of HBsAg was studied, the serum level of HBsAb titer, WBC, PLT, AST, GGT, TBIL, DBIL, CR, PT and PTA were tested daily within the postoperative seven days. The preoperative body weight, serum HBsAg and HBeAg titer were analyzed with the intravenous loading dosage of HBIG by multiple-factor linear regression (Stepwise).

RESULTSBoth the average negative-conversion rate of serum HBsAg and the average increasing rate of serum HBsAb titer are significantly faster in i.v group and domino group than that in i.m group within the postoperative four days (P < 0.05). The regression equation to calculate the i.v loading dosage of HBIG (IU) by preoperative criteria was drawn as 1123 + 3.4 x serum HBsAg titer (IU/L) +73 x body weight (kg). There was no linear correlation found between the level of HBeAg and the loading dosage of HBIG. There were no significant difference in body temperature, pulse rate, respiratory rate, blood pressure, WBC, PLT, AST, GGT, TBIL, DBIL, CR, PT and PTA among the three groups within the postoperative seven days (P < 0.05). The rate of the second elevation of serum ALT was 10.3% (3/29), 3.4% (1/29) and 6.7% (2/30) in i.v group, i.m group and domino group, respectively (P < 0.05), and the rate of the local complications (sclerosis, edema, pain) at the injection site was 0, 89.6% (26/29) and 0, respectively (P < 0.05).

CONCLUSIONSBased on the combined utilization of lamivudine and HBIG, the qualified intervention efficacy, less complications could be obtained by medicating HBIG in a domino way (i.v first, followed by i.m), which is worthy to be promoted.

Alanine Transaminase ; blood ; Antiviral Agents ; administration & dosage ; therapeutic use ; Combined Modality Therapy ; Drug Therapy, Combination ; Hepatitis B ; blood ; prevention & control ; therapy ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Humans ; Immunization, Passive ; methods ; Immunoglobulins ; administration & dosage ; therapeutic use ; Lamivudine ; therapeutic use ; Linear Models ; Liver Transplantation ; Secondary Prevention ; Treatment Outcome

Objective To evaluate the operative outcomes of a triple procedure including simultaneous penetration keratoplasty (PKP),extracapsular cataract extraction (ECCE) and intraocular lens (IOL) implantation,and to investigate the relationship between postoperative corneal refractive power and preoperative lens diopter.Methods This retrospective analysis study involved 15 patients who had undergone a triple procedure surgery in Beijing You'an hospital from April to October 2016.Outcomes including the best corrected visual acuity (BCVA),intraocular pressure (IOP),corneal refractive power,axial length,postoperative complications,corneal endothelial cell counts and the survival of corneal graft were determined one year after surgery.Results All corneal grafts were transparent and corneal endothelium were (1974.20 ±472.82) cell · mm-2.The mean postoperative LogMAR visual acuity (0.80 ±0.27) had a significant improvement compared with the mean preoperative LogMAR visual acuity (2.63 ±0.62) (t =13.042,P ＜0.001).There were no statistically significant differences in preoperative IOP (15.27 ± 2.37) mmHg (1 kPa =7.5 mmHg) and postoperative data (14.53 ± 3.04) mmHg (t =0.685,P =0.505),preoperative axial length (23.69 ±2.01) mm and postoperative data (23.62 ±2.12)mm (t =-0.138,P=0.893)and preoperative keratometry (45.01 ± 1.66) D of the control eye and postoperative data (42.56 ± 5.48) D (t =1.202,P =0.260).The postoperative spherical equivalent refractive was (0.40 ±4.65) D,and the target refraction was (0.58 ±0.25)D.Conclusion The triple procedures are safe and effective for the treatment of patients with coexisting corneal pathologies and cataracts.Selection of emmetropia lens diopter may result in the satisfactory postoperative visual acuity.However,unpredictable postoperative corneal curvature changes will still affect the final refractive state.

Objective To evaluate the efficacy of hot water drinking, isosorbide dinitrate and combination of both in achalasia.Methods The patients with untreated achalasia admitted to Peking Union Medical College Hospital in the period of October 2012 to May 2013 were enrolled and randomly divided into group A ( hot water drinking and combined therapy) and group B (isosorbide dinitrate and combined therapy).Patients in group A received hot water drinking only during the first week, then combined with isosorbide dinitrate from the second to the fourth week.Patients in group B received isosorbide dinitrate only during the first week, then combined with hot water drinking from the second to the fourth week.Clinical symptoms were evaluated at baseline ( 2 weeks before treatment) as well as after 1-week and 4-week treatment.High-resolution manometry and X-ray barium esophagram were evaluated at both baseline and after 4-week treatment.Results A total of 41 patients were in-cluded in this study, 19 in group A and 22 in group B.There was no significant difference in gender, age and course of disease between the two groups ( P>0.05) .Compared with baseline, symptoms were significantly alle-viated after 1-week treatment and after 4-week treatment in group A (P<0.05), and symptoms were significantly mitigated after 4-week treatment than after 1-week treatment ( P<0.05 ) .Compared with baseline, symptoms were significantly alleviated after 4-week treatment in group B ( P<0.05) .There was no difference in scales of symptoms between the two groups (P>0.05).Compared with baseline, there was no significant reduction in lower esophageal sphincter pressure ( LESP) and integrated relaxation pressure ( IRP) after 4-week treatment in both groups (P>0.05).However, at both baseline and after 4-week treatment, LESP and IRP were significantly decreased after hot water drinking or sublingual isosorbide dinitrate compared with pre-intervention levels in both groups ( P<0.05 ) .There was no change in the width of the esophagus after 4-week treatment in both groups ( P>0.05) .Conclusions Hot water drinking or sublingual isosorbide dinitrate could alleviate clinical symp-toms by temporarily decreasing LESP and IPR, which could be amplified by the combination of these two treat-ments, but the effect is not sustained.Hot water drinking combined with sublingual isosorbide dinitrate provides an option of conservative therapy for those intolerant to or relapsing after invasive treatment.

Objective To determine the predictive value of HATCH score on recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA).Methods The data of 123 consecutive AF patients (74 paroxysmal and 49 persistent AF) who underwent RFCA between April 2009 and December 2010 in our department were retrospectively analyzed.Of theses patients,65 (52.9％) patients had HATCH score =0,41 (33.3％) patients had HATCH score =1,and 17 (13.8％) patients had HATCH score ≥2 (HATCH =2 in 11 patients,HATCH =3 in 5 patients,HATCH =4 in 1 patient).The recurrence was defined as atrial tachyarrhythmia lasting more than 30 seconds after 3 months post RFCA.The patients were divided into recurrence group and no recurrence group.Relationship between HATCH score and recurrence was observed.Results There were 43 cases in recurrence group and 80 cases in no recurrence group.After 12 months follow-up,HATCH score was significant higher in recurrence group than in nonrecurrence group[(0.91 ±0.94) score vs.(0.53 ± 0.80) score,P ＜ 0.05].The ratio of patients with HATCH≥2 in recurrence group was higher than in non-recurrence group [23.3％ (10/43) vs.8.8％ (7/80),P ＜ 0.01].The sensitivity and specificity of HATCH ≥ 2 to define the risk of recurrence was 25.0％,92.4％ respectively.Cumulative non-recurrence rate of patients with HATCH score≥2 was lower than patients with HATCH score =0 and 1 (P ＜ 0.05).Conclusion Higher HATCH score is associated with increased risk of AF recurrence post RFCA.