[Recognise of iodine effect on thyroid diseases and metabolism].

Iodine is an essential trace element for human and an antioxidant. It not only participates in the synthesis of thyroid hormone, but also plays a role in metabolic diseases. Previous studies mainly focused on the effect of iodine on thyroid diseases, but ignored the effect on metabolism. After the implementation of the universal salt iodization (USI) of China, the possible consequences of excessive iodine were emphasized while the harm of iodine deficiency was forgetten. The paper re-examines the effects of iodine nutrition on thyroid diseases and metabolism. Iodine deficiency can lead to an increased risk of iodine deficiency disorders and thyroid diseases, and increase prevalence of metabolic syndrome and its components. Moderate iodine excess is beneficial to metabolism, but it can increase the risk of hyperthyroidism and subclinical hypothyroidism. The average urinary iodine concentration in 100-299 µg/L is the appropriate iodine nutrition state. According to the present iodized content of salt in China, iodized salt is an economical and effective way to ensure adequate iodine nutrition.

[Survey on the prevalence and related factors of thyroid disorders in different iodine intake regions in China in 2015-2017].

Objective: To observe the prevalence and related factors of thyroid diseases in different iodine intake areas from 2015 to 2017 after the implementation of national salt iodization policy in China for 20 years. Methods: A cross-sectional survey. Multi-stage stratified cluster random sampling was used to randomly select subjects meeting the inclusion criteria from 31 provinces, municipalities and autonomous regions in China from January 2015 to December 2017, and stratified by age and sex. The survey included questionnaire, physical examination and thyroid ultrasonography. At the same time, the concentrations of serum thyrotropin, thyroxine, thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urinary iodine were measured.To determine whether the patient has a certain thyroid disease according to the above results. Different iodine nutrition areas were defined according to urinary iodine concentration, and the influence of iodine nutrition status in different iodine intake areas on thyroid diseases was analyzed. Results: A total of 78 470 adults were included, including 39 893 in the area of moderate iodine, 28 779 in the area of adequate iodine, and 9 798 in the area of excessive iodine.In the above three regions, the prevalence of subclinical hyperthyroidism (hyperthyroidism) was 0.45% (95%CI: 0.39%-0.52%), 0.50%(95%CI: 0.35%-0.70%)and 0.27%(95%CI: 0.20%-0.35%), respectively, with statistical significance(χ²=6.92, P=0.003). The prevalence of subclinical hypothyroidism (hypothyroidism) was 11.36% (95%CI: 10.73%-12.02%), 13.57%(95%CI: 11.70%-15.69%) and 16.18%(95%CI: 12.41%-20.82%), respectively, with statistical significance(χ²=5.08, P=0.009). The prevalence rates of Graves' disease, TPOAb, goiter and thyroid nodule among the three regions were statistically significant (all P<0.05). There were no significant differences in the prevalence of clinical hyperthyroidism and clinical hypothyroidism and the positive rate of TgAb among the three regions (all P>0.05). Multivariate logistic regression model analysis showed that excess iodine was a risk factor for subclinical hypothyroidism (OR=1.24, 95%CI: 1.06-1.44), and a protective factor for thyroid nodules (OR=0.73, 95%CI: 0.57-0.94). Iodine overdose was a risk factor for subclinical hypothyroidism (OR=1.47, 95%CI: 1.08-2.01), while it was a protective factor for subclinical hyperthyroidism (OR=0.56, 95%CI: 0.41-0.77), and TPOAb positive (OR=0.93, 95%CI: 0.87-0.99), goiter (OR=0.33, 95%CI: 0.17-0.66) and thyroid nodule (OR=0.77, 95%CI: 0.61-0.97). Conclusions: There are significant differences in the prevalence of subclinical hyperthyroidism, subclinical hypothyroidism, positive TPOAb, thyroid nodule and goiter in different iodine intake regions. Different iodine intake levels have an effect on the incidence of thyroid diseases.

Activation of Nrf2 signaling by 4-octyl itaconate attenuates the cartilaginous endplate degeneration by inhibiting E3 ubiquitin ligase ZNF598.

OBJECTIVE: Cartilaginous endplate (CEP) degeneration is the main early manifestations of intervertebral disc degeneration (IVDD), and is closely related to the oxidative stress. Nrf2 (nuclear factor E2-related factor 2, NFE2L2) is a vital transcriptional factor of cellular antioxidant and anti-inflammatory responses. We aimed to illustrate whether the Nrf2 which was increased in expression by 4-octyl itaconate (4OI) could attenuate intervertebral disc degeneration through suppressing macrophage associated inflammation and catabolism of cartilaginous endplate. METHODS: Firstly, we detected the expression of Nrf2 in human degenerative CEPs. Then, we performed in vitro, ex vivo and in vivo (a rat-tail puncture model) experiments to explore the role of 4OI in IVDD. Also, by cell co-culture experiments, we demonstrated 4OI restrained the macrophage-associated inflammatory responses. Finally, through western blotting and immunoprecipitation (IP) assay, we clarified the ZNF598-mediated ubiquitination of Nrf2. RESULTS: We found decreased expression of Nrf2 in human degenerative CEPs. Using a rat IVDD model(n = 6), 4OI significantly ameliorated the progression of IVDD by MR images and histological analysis. Immunofluorescence results reveal that catabolism of CEPs and macrophage-associated inflammation are suppressed by 4OI treatment. Mechanistically, the 4OI increases Nrf2 expression and inhibits the secretion of inflammatory factors (IL-1ß) by Lipopolysaccharide (LPS)-induced macrophages, thus preventing the inflammatory-related CEP degeneration. Meanwhile, 4OI suppresses the reactive oxygen species (ROS) production and catabolism of LPS-induced rat CEP cells. In addition, 4OI inhibits the ZNF598-dependent ubiquitination of Nrf2 in LPS-induced rat CEP cells. CONCLUSIONS: 4OI may alleviate IVDD by suppressing CEP degeneration and macrophage-associated inflammation. 4OI may be an alternative therapy for degenerative CEPs/IVDs.

[Effects of cortical bone trajectory screw in adjacent-segment disease after posterior lumbar interbody fusion].

Objective: To investigate the effect of the cortical bone trajectory (CBT) screw fixation combined with midline lumbar fusion (MIDLF) for adjacent spondylopathy after posterior lumbar interbody fusion. Methods: A retrospective analysis was conducted in 16 patients, including 9 males and 7 females, with a mean age of (68±6) years, who underwent revision surgery for adjacent spondylopathy after posterior lumbar fusion surgery using CBT combined with MIDLF technology in Sir Run Run Shaw Hospital, Zhejiang University from May 2013 to August 2019. The reasons for revision were radiculalgia in 4 cases, intermittent claudication in 10 cases and protrusive dissociate in 2 cases. Eleven cases had 1 segment fused in the first operation, while the other 5 cases received fusion in 2 segments. The average interval time between the first operation and the revision operation was (7.5±2.0) years. For the levels underwent revision, 1 case was L2/3, 6 cases were L3/4, 7 cases were L4/5 and 2 cases were L5/S1. Before the operation, all the patients took X-rays scans of the thoracic and lumbar spine. CT and MRI scans were also performed. The operation time, intraoperative bleeding, surgical complications, visual analog scale (VAS) of low back and leg pain before the operation and at each follow-up were all recorded. Oswestry disability index (ODI) questionnaire was used to evaluate the functional improvement of patients after the operation. Results: All operations were completed successfully. The operation time was 120-240 (170±30) mins, intraoperative bleeding was 100-280 (220±45) ml. One case had a slight split in the isthmus, and the screw was inserted smoothly after adjusting the insertion point. In one case, the cerebrospinal fluid leaked during the operation and was successfully treated with conservative methods including no pillow supine treatment and strengthened anti-infection. The average follow-up time was of (19.5±1.3) months. The VAS of low back pain was 2.9±1.7 before the operation and it was 1.8±0.5 at the last follow-up, and the difference was statistically significant (P<0.01). The VAS of leg pain was 5.9±1.5 before the operation and it was 1.5±0.4 at the last the follow-up (P<0.01). The ODI score was 34.5±3.2 preoperatively and it decreased to 12.6±4.2 at the last follow-up, the difference was statistically significant (P<0.01). Conclusion: CBT technique combined with MIDLF for the adjacent-segment disease after posterior lumbar interbody fusion is minimally invasive and convenient, with good clinical effects. This technique can be used as an option for the revision of adjacent spondylopathy.

[Efficacy and safety of Changsulin® compared with Lantus® in type 2 diabetes: a phase â ¢ multicenter, randomized, open-label, parallel, controlled clinical trial].

Objective: To compare the efficacy and safety of Changsulin® with Lantus® in treating patients with type 2 diabetes mellitus (T2DM). Methods: This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin® or Lantus® treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results: After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin® and in Lantus®, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin® and Lantus® in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin® and Lantus®, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin® and Lantus®, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions: Changsulin® shows similar efficacy and safety profiles compared with Lantus® and Changsulin® treatment was well tolerated in patients with T2DM.

Association between iodine intake and thyroid autoantibodies: a cross-sectional study of 7073 early pregnant women in an iodine-adequate region.

PURPOSE: The association between iodine intake and thyroid autoimmunity has been debated, especially in pregnant women. This study aimed to investigate thyroid autoantibodies and their association with iodine intake and hypothyroidism in early pregnancy. METHODS: 7073 early pregnant women from an iodine-sufficient region participated in this study. Urinary iodine concentrations (UICs) were measured using an ammonium persulfate method. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and Tg were determined using an electrochemiluminescence immunoassay. RESULTS: Iodine deficiency (UIC < 100 µg/L) was associated with higher risks of TPOAb positivity [adjusted odds ratio (aOR) = 1.64, 95% confidence interval [CI] (1.29-2.08)] and TgAb positivity [aOR = 1.44, 95% CI (1.16-1.80)]. Women with isolated TPOAb positivity, isolated TgAb positivity, or both TPOAb and TgAb positivity had a 14.64-fold, 7.83-fold, and 44.69-fold increased risk of overt hypothyroidism, and a 4.36-fold, 2.86-fold, and 6.26-fold increased risk of subclinical hypothyroidism, respectively. Moreover, the risks of overt and subclinical hypothyroidism in women with a high TPOAb titer were 16.99 and 4.80 times that in TPOAb-negative women, respectively. The risk of overt hypothyroidism in women with a high TgAb titer was 6.97 times that in TgAb-negative women. CONCLUSIONS: Our work demonstrates that iodine deficiency during early pregnancy is an independent risk factor for both TPOAb positivity and TgAb positivity. Furthermore, positivity for both autoantibodies and a high thyroid autoantibody titer are associated with significantly higher risks of overt and subclinical hypothyroidism.

[Analyses of audiological examination in children without auditory brainstem response].

Objective: To investigate residual hearing of children severe and profound sensorineural deafness in whom wave V was not found in auditory brainstem response(ABR) testing, and to emphasize the importance of objective audiological tests. Methods: Two hundred and fifty-two children who were admitted to the Second Affiliated Hospital of Zhengzhou University between January 2015 and April 2018, with an average age of 20 months from 72 days to 4 years, received a full battery of objective audiological tests consisting of distortion product otoacoustic emission(DPOAEs), tympanometry, auditory brainstem responses(ABRs), 40 Hz auditory event related potential(40 HzAERP) and auditory steady-state response(ASSRs).There were 159 males(318 ears) and 93 females(186 ears). Residual hearing obtained by 40 HzAERP、ASSR of 252 children with sensorineural deafness was studied in relation to the absence of wave V in click ABR. SPSS 16.0 software was used to analyze the data. Results: Four hundred and forty-four ears of 504 ears have residual hearing of different degrees at different frequencies(88.1%),60 ears (11.9%) were found in whom responses was not found in 40 HzAERP、ASSR testing; Seventy-two ears(14.3%) in 38 patients were tested cochlear microphonic potentials (CMs). Conclusion: In children hearing evaluations,a full battery of objective audiological tests could better investigate residual hearing; The CMs were tested could provide the Audiotery Neuropathy diagnosis in infants with OAEs and ABR absent.

[Genetic characteristic of hemagglutinin of avian influenza A (H7N9) virus in Guizhou Province in 2017].

The number of H7N9 bird flu cases was high and the situation was grim in guizhou province in 2017. To understand the molecular characteristics of the hemagglutinin gene (HA) and the risk of human infection with avian influenza virus A(H7N9) in Guizhou Province, 2017. Homology, genetic evolution and pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of 14 avian influenza viruses A(H7N9) were analyzed by a series of bioinformation softwares. It was cleared that there was 95.9%-100% similarity among 14 strains in nucleotide of the HA gene, and there were 96.8%-97.8% and 96.8%-97.9% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Phylogenetic analysis showed that 14 HA genes were directly evolved in the Yangtze River Delta evolution branch, but they could be derived from five diffenrent strains. Then 13 of 14 strains cleavage site sequences of HA protein revealed they were low pathogenic avian influenza viruses, while A/Guizhou-Weining/CSY01/2017 was high pathogenic avian influenza virus. Mutation G186V at the receptor binding sites in the HA was found in all 14 strains, and mutation Q226L in 13 strains besides A/Guizhou-Weining/CSY01/2017. All five potential glycosylation motifs in the HA were conservative.

The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China.

OBJECTIVES: To explore the effect of isolated maternal hypothyroxinemia (IMH) during the first and second trimester of gestation on pregnancy outcomes. To explore whether levothyroxine (L-T4) treatment of women who had IMH identified in the first trimester improves pregnancy outcomes. METHODS: Women in the early pregnancy in the iodine-sufficient area (n = 3398) were recruited to this prospective cohort study (ChiCTR-TRC-12002326). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were detected. Women with IMH before 12 weeks chose to receive L-T4 or remain untreated. The L-T4 dose was adjusted to attain a normal FT4 and TSH level. Pregnancy outcomes were evaluated during follow-up. RESULTS: IMH in the first trimester was not associated with increased risk of adverse pregnancy outcome compared with controls. The incidence of macrosomia (p = 0.022) and gestational hypertension (p = 0.018) was significantly higher in IMH identified in the second trimester of gestation compared with controls. IMH identified in the second trimester of gestation was a risk factor for macrosomia [adjusted odds ratio (aOR) 1.942, 95% CI 1.076-3.503, p = 0.027] and gestational hypertension (aOR 4.203, 95% CI 1.611-10.968, p < 0.01), when body mass index in the early pregnancy was < 25 kg/m2. CONCLUSIONS: IMH in the first trimester did not increase the risk of adverse outcomes irrespective of whether women received L-T4 treatment. However, IMH identified in the second trimester was associated with increased risk of adverse pregnancy outcome. The results suggest that thyroid function follow-up during the second trimester is necessary, even if thyroid function is normal during the first trimester.

Meta-analysis of ART outcomes in women with different preconception TSH levels.

BACKGROUND: To assess whether elevated thyroid-stimulating hormone (TSH) levels before conception can predict poor outcomes of assisted reproductive technology (ART). METHODS: Prior to July 2018, we searched the PubMed, EMBASE, COCHRANE, Google Scholar, and CNKI databases for studies. Retrospective or prospective reports that compared ART results in patients with subclinical hypothyroidism (SCH) with normal thyroid function were selected. Two reviewers separately reviewed each potential article for qualification, analyzed the quality of the studies according to the Newcastle-Ottawa scale, and extracted the data. The PRISMA guidelines were adopted. RESULTS: We selected a total of 18 publications that included 14,846 participants for this meta-analysis. When the TSH cut-off value for SCH was set at 2.5 mIU/L, no significant differences were observed in ART-related outcomes between SCH patients and normal women. The evaluated outcomes included the live birth rate (LBR) (OR: 0.93; 95% CI (0.77,1.12), P = 0.43), clinical pregnancy rate (CPR) (OR:1.02; 95% CI (0.90,1.17); P = 0.74), pregnancy rate (PR) (OR: 1.00; 95% CI (0.89,1.12); P = 0.99), and miscarriage rate (MR) (OR:1.24; 95% CI (0.85, 1.80); P = 0.26). Furthermore, when a higher TSH level was used as the cut-off value to diagnose SCH (i.e., 3.5-5 mIU/L), a significant difference was found in the MR (OR: 1.91; 95% CI (1.09, 3.35); P = 0.02) between the two groups of ART-treated women. However, when a broader cut-off value was used to define SCH, no significant differences were observed in the LBR (OR: 0.72; 95% CI (0.47,1.11); P = 0.14), CPR (OR: 0.82; 95% CI (0.66,1.00); P = 0.052), or PR (OR: 1.07; 95% CI (0.72,1.60); P = 0.74) between the two groups of ART-treated women. CONCLUSION: No difference was observed in ART outcomes when a TSH cut-off value of 2.5 mIU/L was used. However, when a broader TSH cut-off value was used, preconception SCH resulted in a higher miscarriage rate than in normal women.

Subclinical hypothyroidism and depression: a meta-analysis.

The objective of this study was to evaluate the relationship between subclinical hypothyroidism (SCH) and depression. We also analysed the effect of levothyroxine (L-T4) on depression in SCH patients. We found an insignificant difference for the composite endpoint: standard mean difference (SMD) of 0.23 (95% confidence interval (CI) -0.03, 0.48, P = 0.08, I2 = 73.6%). The odds ratio (OR) for depressive patients was 1.75 (95% CI 0.97, 3.17 P = 0.064, I2 = 64.6%). Furthermore, sub-group analysis according to age found that SCH was related to depression in younger patients (<60 years old), as defined by the diagnosis of depression: OR of 3.8 (95% CI 1.02, 14.18, P = 0.047, I2 = 0.0%) or an increase on the depressive scale: SMD of 0.42 (95% CI 0.03, 0.82, P = 0.036, I2 = 66.6%). Meanwhile, SCH did not associate with depression in older patients (≥60 years old), as defined by the diagnosis of depression: OR of 1.53 (95% CI 0.81, 2.90, P = 0.193, I2 = 71.3%) or an increase on the depressive scale: SMD of 0.03 (95%CI -0.31, 0.37, P = 0.857, I2 = 79.8%). We also found an insignificant difference in the composite endpoint between the L-T4 supplementation group and placebo group in SCH patients. The estimated SMD was 0.26 (95% CI -0.09, 0.62, P = 0.143, I2 = 52.9%). This meta-analysis demonstrates that SCH is not connected to depression. However, sub-group analysis according to age found that SCH is related to depression in younger patients, but not in older patients. Furthermore, we failed to find an effect of L-T4 supplementation treatment for SCH on depression.

Expressions and effects of G250, Bax and Bcl-2 in rats with renal clear cell carcinoma.

OBJECTIVE: To investigate the expressions and effects of G250, B-cell lymphoma-2 associated X protein (Bax) and Bcl-2 in rats with renal clear cell carcinoma (RCCC). MATERIALS AND METHODS: A total of 66 male Sprague-Dawley (SD) rats were selected, among which 56 were selected to establish RCCC rat model and the remaining 10 were selected as control group. Three weeks after modeling, 4 rats failed in the modeling. Expressions of G250 in RCCC rat model group and healthy rat model control group were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR); expressions of Bcl-2 and Bax in each group were detected by Western blot and their effects were analyzed. RESULTS: The positive expression rates of G250 in 52 RCCC rats in model group and 10 healthy rats in control group were 83.3% and 0%, respectively. The results showed that expression of G250 had a certain correlation with the pathological changes of RCCC (p < 0.01). Expressions of Bax and Bcl-2 were up-regulated in the RCCC group, while expressions were down-regulated in the healthy control group (p < 0.05). CONCLUSIONS: G250, as a new specific marker of renal cell carcinoma, is involved in the pathological changes of renal cell carcinoma. Joint detection of Bax and Bcl-2 can be used as an important index for the diagnosis of RCCC.

Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide.

This study was carried out to determine the incidence of hepatitis B virus (HBV) infection in the young generation born after mandatory implementation of hepatitis B vaccination since 1992. Repeat blood donors born between 1992 and 1997 were enrolled, who gave blood at least twice during the past 3 years. Donors were tested for HBV infection markers of HBsAg, anti-HBc, anti-HBs and viral DNA by immunoassays (EIAs) and nucleic acid tests (NAT). A total of 14 937 pre-donation screening qualified young repeat donors aged 18-23 years were tested with 9 (0.06%) being HBsAg by EIA and 10 (1:1494) HBV DNA positive by Ultrio NAT (10.4 IU/mL), respectively. HBV DNA was further detected in 1:192 (9/1732) anti-HBc+ repeat donors with Ultrio Plus NAT (3.4 IU/mL). Most cases were identified as occult HBV infection (OBI). Of 14 937 repeat donors, 20.9% were anti-HBc+ positive, while approximately 50% of 12 024 repeat donors were anti-HBs negative or had levels <100 IU/L. HBsAg+ or OBI strains were classified as wild type of genotype B or genotype C. Incident HBV infection in repeat donors was approximately 1:18.5 person-years (1.1%/year) but significantly less frequent in donors with confirmed HBV vaccination (2.4%-3.3%) than those unsure of vaccination status (10.5%; P = .0023). Hepatitis B virus vaccination appears largely protective of HBV infection, but incidence of infections increases in young adults with mostly undetectable or low anti-HBs or occasionally high anti-HBs. A boost of hepatitis B vaccine for adolescents prior to age 18 years may reduce HBV infection, and implementation of more sensitive NAT in blood donation screening may improve HBV safety in blood transfusion.

[Clinical analysis of chronic sternal osteomyelitis with sinus tract after cardiovascular surgery].

Objective: To explore the diagnosis, therapy and prevention method of chronic sternal osteomyelitis with sinus tract after cardiovascular surgery. Methods: A total of 53 patients with chronic sternal sinus tract after cardiovascular surgery between January 2000 and January 2016. After definite diagnosis by contrast fistulography and CT scanning, all the patients received combined modality therapy including debridement, musculocutaneous flap transplantation and intermediate thickness free skin graft transplantation if necessary. Results: One patient died of false aneurysm due to the sternal sinus tract infection, there were no peri-operative death for all the left 52 patients. Forty-five patients had primary healing and 7 patients had secondary healing. All the patients became total recovery within 3-12 weeks after operation and maintained well during the 5-18 months' follow-up. Conclusions: For the patients with chronic sternal osteomyelitis, operative therapy should be performed as soon as possible once the diagnosis is confirmed. Combined modality therapy including debridement, musculocutaneous flap transplantation and intermediate thickness free skin graft transplantation is confirmed to be effective and secure.

Molecular evolution of hepatitis C virus in China: A nationwide study.

The evolutionary and epidemic history and the regional differences of hepatitis C virus (HCV) are complex and remain unclear in the vast territory China. Here we recruited 1540 HCV-RNA positive patients sampled in 29 provinces across whole China, which is the largest sample capacity and the most comprehensive geographic coverage of China to our knowledge. 1b, 2a, 3b, 6a and 3a were the major subtypes in China. 1b was the most predominant subtype which presented in every province. The second most predominant subtype, 2a, appeared to concentrate in the north of China. Subtypes 3a and 3b were mainly found in the Southwest region, while 6a was restricted in the South region. We further estimated the origins of the dominating subtypes and discovered for the first time that a Chinese-specific transmission pattern for some strains of subtype 2a which was restricted in north China, and Chinese subtype 3b originated from Thailand.

Osteochondral Interface Stiffening in Mandibular Condylar Osteoarthritis.

Osteoarthritis (OA) of the temporomandibular joint (TMJ) is associated with dental biomechanics. A major change during OA progression is the ossification of the osteochondral interface. This study investigated the formation, radiological detectability, and mechanical property of the osteochondral interface at an early stage, the pathogenesis significance of which in OA progression is of clinical interest and remains elusive for the TMJ. Unilateral anterior crossbite (UAC) was performed on 6-wk-old rats as we previously reported. TMJs were harvested at 4, 12, and 20 wk. The progression of TMJ OA was evaluated using a modified Osteoarthritis Research Society International (OARSI) score system. Osteochondral interface was investigated by quantifying the thickness via von Kossa staining of histological slices and in vivo calcium deposition by calcein injection. Tissue ossification was imaged by micro-computed tomography (CT). Mechanical properties were measured at nanoscale using dynamic indentation. Time-dependent TMJ cartilage lesions were elicited by UAC treatment. Geometric change of the condyle head and increased value of the OARSI score were evident in UAC TMJs. At the osteochondral interface, there was not only enhanced deep-zone cartilage calcification but also calcium deposition at the osseous boundary. The thickness, density, and stiffness of the osteochondral interface were all significantly increased. The enhanced ossification of the osteochondral interface is a joint outcome of the aberrant deeper cartilage calcification at the superior region and promoted formation of subchondral cortical bone at the inferior region. The micro-CT detectable ossification from an early stage thus is of diagnostic significance. Although the environment of the cartilage and subchondral bone could be changed due to the stiffness of the interface, whether or not the stiffened interface would accelerate OA progress remains to be confirmed. With that evidence, the osteochondral interface could be a new diagnostic and therapeutic target of the mechanically initiated OA in the TMJ.

Orexin A increases sympathetic nerve activity through promoting expression of proinflammatory cytokines in Sprague Dawley rats.

AIM: Accumulating evidence suggests that orexin signalling is involved in the regulation of blood pressure and cardiovascular function. However, the underlying mechanisms are not clear. Here, we test the hypothesis that upregulated orexin A signalling in the paraventricular nucleus (PVN) increases sympathetic nerve activity (SNA) through stimulating expression of proinflammatory cytokines (PICs). METHODS: In vivo sympathetic nerve recordings were performed to test the impact of PVN orexin signalling on sympathetic outflow in Sprague Dawley (SD) rats. Real-time PCR was carried out to assess effects of central administration of orexin A on PVN PICs expression in SD rats. To test whether orexin A-induced increases in PICs were exclusively mediated by orexin receptor 1 (OX1R), OX1R-expressing PC12 (PC12-OX1R) cells were incubated with different dose of orexin A, and then, PICs mRNA and immunoreactivity were measured. RESULTS: Orexin A microinjection (25 pmol) into the PVN significantly increased splanchnic SNA (93.5%) and renal SNA (83.3%) in SD rats, and these increases were attenuated by OX1R antagonist SB408124. Intracerebroventricular injection of orexin A (0.2 nmol) into SD rats increased mRNA levels of PICs including IL-1-ß (2.7-fold), IL-6 (1.7-fold) and TNF-α (1.5-fold), as well as Fra1 (1.6-fold) in the PVN. Orexin A treatment in PC12-OX1R cells resulted in a dose- and time-dependent increase in the expression of PICs and Fra1, a subunit of AP1 transcriptional factor. The increase in the PICs was blocked by AP1 blocker curcumin. CONCLUSION: Paraventricular nucleus orexin system activation is involved in SNA regulation maybe through triggering AP1-PICs pathway.