[Serum immunoglobulin concentration and the risk of type 2 diabetes mellitus in adults in Tianjin City: a prospective cohort study].

Objective: To evaluate the association between immunoglobulin concentration and the risk of type 2 diabetes mellitus (T2DM) in adults in Tianjin City. Methods: Based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort from January 2010 to December 2018, subjects who had completed the measurement of baseline immunoglobulin concentration and blood glucose concentration and not been diagnosed with any type of diabetes at baseline were selected in this study. The collected data included the concentration of serum immunoglobulin (IgG, IgM, IgA and IgE), fasting blood glucose and other potential confounders. The subjects were divided into four groups from Q1 to Q4 according to the quartiles of baseline immunoglobulin concentration. The multivariable Cox regression model was used to assess the association between the baseline immunoglobulin concentration and T2DM. Results: A total of 6 315 subjects aged (50.1±10.0) years were included. About 390 subjects were newly diagnosed with T2DM during the follow-up period. The incidence rate was 16.8/1 000 person-years. After adjusting for age, sex, waist circumference, smoking status, drinking status, eosinophil ratio, metabolic syndrome, first-or second-degree family history, and reciprocal adjusting for other immunoglobulin concentrations, compared to the lowest quartile concentration group Q1, subjects in group Q4 with the highest quartile of IgG concentration showed a lower risk of T2DM (HR=0.71, 95%CI: 0.52-0.97), and subjects in group Q4 with the highest quartile of IgM concentration also had a decreased risk of T2DM (HR=0.66, 95%CI: 0.47-0.91). Subjects in group Q4 with the highest quartile of IgA concentration had an increased risk of T2DM (HR=1.56, 95%CI: 1.18-2.07). The risk of T2DM decreased with the increase of serum IgG and IgM concentrations (Ptrend=0.018, Ptrend=0.010) and increased with the increase of serum IgA concentrations (Ptrend<0.001). No association was found between the concentration of IgE and T2DM risk (HR=0.99, 95%CI: 0.74-1.31, Ptrend=0.891). Conclusion: The concentration of IgG and IgM is negatively associated with the risk of T2DM, and the concentration of IgA is positively associated with the risk of T2DM in Tianjin City. The concentrations of IgG, IgM and IgA could be a predictor of hyperglycemia and T2DM.

[Effects of small GTP-binding protein GDP dissociation stimulator on adipocyte hypertrophy and glucose metabolism disorder in mice].

Objective: To explore the effect and mechanism of small GTP-binding protein GDP dissociation stimulator (SmgGDS) on the development of obesity. Methods: (1) 8-week-old C57BL/6J mice were randomly assigned to normal diet and high fat diet group, with 6 mice in each group. They were fed regular feed and a high fat diet containing 60% fat for 4 months, respectively. The expression of SmgGDS in epididymal adipose tissue (eWAT), liver, and skeletal muscle were measured using Western-blot. (2) 6-week-old wild-type (WT) and SmgGDS knockdown (KD) mice were divided into four groups, each receiving high fat diet for 4 months (7 in each group) and 7 months (9 in each group). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted; The weight, adipose tissue, and liver weight of mice were recorded; HE staining examined adipose tissue structural changes; Western-blot determined extracellular signal-regulated kinase (ERK) 1/2 phosphorylation levels in eWAT; Real time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA levels of CCAAT/enhancer binding protein α (C/EBPα), C/EBPß and peroxisome proliferator activated receptor γ (PPARγ) in eWAT. (3) Mouse embryonic fibroblasts (MEFs) extracted from WT and KD mice were induced for differentiation. Oil red O staining and Western-blot were used to detect lipid droplet and expression of SmgGDS and phospho-ERK; C/EBPα, C/EBPß and PPARγ mRNA levels were measured using RT-qPCR. (4) 10-week-old C57BL/6J mice were randomly assigned into two groups, with 7 mice in each group. Mice were infected with SmgGDS overexpressing adeno-associated virus (AAV-SmgGDS) or empty vector intraperitoneally, then fed with high fat diet. After 4 weeks, performed GTT and ITT; Recorded the weight and adipose tissue weight of mice; HE staining was used to analyze structural changes of eWAT; Western-blot was used to detect the phosphorylation level of ERK in eWAT. Results: (1) The expression of SmgGDS was significantly upregulated in eWAT of high fat diet fed mice (normal diet group: 0.218±0.037, high fat diet group:0.439±0.072, t=2.74, P=0.034). (2) At 4 months of high fat diet intervention, the glucose tolerance (60 minutes after glucose injection, WT group: 528 mg/dl±21 mg/dl, KD group: 435 mg/dl±17 mg/dl, t=3.47, P=0.030; 90 minutes, WT group: 463 mg/dl±24 mg/dl, KD group: 366 mg/dl±18 mg/dl, t=3.23, P=0.047;120 minutes, WT group: 416 mg/dl±21 mg/dl, KD group: 297 mg/dl±16 mg/dl, t=4.49, P=0.005) and insulin sensitivity (15 minutes after insulin injection, WT group: 77.79%±3.45%, KD group: 54.30%±2.92%, t=3.49, P=0.005; 30 minutes, WT group: 62.27%±5.31%, KD group: 42.25%±1.85%, t=2.978, P=0.024; 90 minutes, WT group: 85.69%±6.63%, KD group: 64.71%±5.41%, t=3.120, P=0.016) of KD mice were significantly improved compared to the WT group, with an increase in eWAT weight ratio (WT: 4.19%±0.18%, KD: 5.12%±0.37%, t=2.28, P=0.042), but a decrease in average adipocyte area (WT group: 5221 µm²±241 µm², KD group: 4410 µm²±196 µm², t=2.61, P=0.026). After 7 months of high fat diet, the eWAT weight ratio of KD mice decreased (WT: 5.02%±0.20%, KD: 3.88%±0.21%, t=3.92, P=0.001) and adipocyte size decreased (WT group: 6 783 µm²±390 µm², KD group: 4785 µm²±303 µm², t=4.05, P=0.002). The phospho-ERK1 in eWAT increased (WT group: 0.174±0.056, KD group: 0.588±0.147, t=2.64, P=0.025), and mRNA level of PPARγ significantly decreased (WT group: 1.018±0.128, KD group: 0.029±0.015, t=7.70, P=0.015). (3) The expression of SmgGDS was significantly increased in differentiated MEF (undifferentiated: 6.789±0.511, differentiated: 10.170±0.523, t=4.63, P=0.010); SmgGDS knock-down inhibited lipid droplet formation in MEF (WT group: 1.00±0.02, KD group: 0.88±0.02, t=5.05, P=0.007) and increased ERK1 (WT group: 0.600±0.179, KD group: 1.325±0.102, t=3.52, P=0.025) and ERK2 (WT group: 2.179±0.687, KD group: 5.200±0.814, t=2.84, P=0.047) activity, which can be reversed by ERK1/2 inhibitor. (4) SmgGDS over expression resulted in weight gain, increased eWAT weight (control group: 3.29%±0.36%, AAV-SmgGDS group: 4.27%±0.26%, t=2.20, P=0.048) and adipocyte size (control group: 3525 µm²±454 µm², AAV-SmgGDS group: 5326 µm²±655 µm², t=2.26, P=0.047), impaired insulin sensitivity(30 minutes after insulin injection, control group: 44.03%±4.29%, AAV-SmgGDS group: 62.70%±2.81%, t=3.06, P=0.019), and decreased ERK1 (control group: 0.829±0.077, AAV-SmgGDS group: 0.326±0.036, t=5.96, P=0.001)and ERK2 (control group: 5.748±0.287, AAV-SmgGDS group: 2.999±0.845, t=3.08, P=0.022) activity in eWAT. Conclusion: SmgGDS knockdown improves obesity related glucose metabolism disorder by inhibiting adipogenesis and adipose tissue hypertrophy, which is associated with ERK activation.

[Application and progress of photodynamic therapy in combination therapy of lung cancer].

Lung cancer is one of the most common malignant tumors with high morbidity and mortality. At present, the traditional treatments of lung cancer include surgical resection, radiotherapy, chemotherapy, targeted therapy and immunological therapy. The modern model of diagnosis and treatment tends to be multidisciplinary, individual, focusing on systemic therapy combined with local therapy. Recently, PDT(photodynamic therapy) becomes an emerging cancer treatment due to its advantages of low trauma, high selectivity, hypotoxicity, good reutilization. PDT has a good effect in the radical treatment of early airway cancer and palliative treatment of advanced airway tumor by using its photochemical reactions. Nevertheless, more attention is focused on combination therapy of PDT Combination with surgery can reduce tumor burden and eliminate potential lesions; Combination with radiotherapy can reduce the amount of radiation and improve therapeutic effect; Combination with chemotherapy achieves the combination of local and systemic therapy; Combination with targeted therapy can enhance anti-cancer targeting; combination with immunotherapy can improve anti-cancer immunity, etc. This article focused on PDT as a part of a combination therapy in the treatment of lung cancer, to provide a new treatment method for patients with poor therapeutic effect with traditional treatment.

[Effect of daily average temperature on the incidence of allergic rhinitis in Lanzhou].

Objective: To evaluate the effect of daily average temperature on the atteck of allergic rhinitis (AR) by analyzing the changes of the outpatient visits of AR in Lanzhou. Methods: The meteorological and air pollution data of Lanzhou City and the outpatient visits of AR in Departments of Otorhinolaryngology and head and neck surgery of The First Hospital of Lanzhou University, The Second Hospital of Lanzhou University and Gansu Provincial People's Hospital from 2013 to 2017 were collected to describe the meteorological factors, air pollutants and the outpatient visits of AR. The correlation among the three factors was then analyzed by Spearman rank correlation analysis. Using the distributed lag non-linear model, the relationship between daily average temperature and the number of daily outpatient visits of AR was studied and stratified by gender and age with the long-term trend, seasonal trend and other confounding factors controlled. Results: From 2013 to 2017, the outpatient visits of AR in the above three hospitals reached 20 008 person times. Daily average temperature in Lanzhou showed a non-linear correlation to the outpatient visits of AR, with a certain lag effect. When the daily average temperature was 22 ℃ and the cumulative lag was 21 days (lag 0-21 d), the relative risk (RR) peaked at 4.851 (95%CI: 3.986-5.904). The effect of relatively low temperature (2.3 ℃, P25), relatively high temperature (19.8 ℃, P75) and high temperature (25.5 ℃, P95) on lag 0-21 d were the highest, which were 1.761 (95%CI: 1.375-2.255), 4.299 (95%CI: 3.574-5.171) and 3.656 (95%CI: 3.046-4.389), respectively. According to the stratified analysis, low and relatively low temperature had more significant effect on the outpatient visits of AR among women and people aged 0-14 years. When lag was 0-21 days, the RR value of low temperature for female outpatient visits of AR was 1.433 (95%CI: 1.105-1.860); the RR value of relatively low temperature for female outpatient visits of AR was 1.879 (95%CI: 1.460-2.419); the RR value of low temperature for AR outpatient visits for people aged 0-14 years was 1.511 (95%CI: 0.999-2.287), the RR value of relatively low temperature for AR outpatient visits for people aged 0-14 years was 2.051 (95%CI: 1.383-3.042). Relatively high temperature, on the other hand, had a more significant effect on men and people aged 15-59 years. High temperature had a greater impact on the number of AR outpatients in men and people aged 0-14 years. Conclusions: Temperature may be an important influencing factor of AR onset in Lanzhou. At relatively high temperature (19.8 ℃), the risk of AR outpatient visits is significantly increased, and the cumulative lagged effects are observed. The sensitivity of AR patients to temperature is different in different genders and ages.

[Evaluation of unilateral and bilateral bimodal bone conduction hearing intervention in patients with bilateral microtia-atresia].

Objectives: To evaluate the therapeutic effects of unilateral/bilateral bone conduction hearing rehabilitation in patients with bilateral microtia accompanied with severe conductive hearing loss following staged auricle reconstruction and bonebridge implantation. Methods: Thirty-two patients, including 20 males and 12 females, with an average age of 11.8, who received surgical treatment in Peking Union Medical College Hospital (PUMCH) from March, 2016 to January, 2020 with bilateral microtia-atresia were included. Hearing thresholds, speech perception and high-resolution CT of the temporal bone were evaluated prior to surgery and individualized surgery plans (staged auricle reconstruction and bonebridge implantation) were made. Hearing thresholds and speech perception in quiet and noise (SNR = 5 dB) using unilateral Bonebridge were tested two weeks after the implantation surgery when the Bonebridge was activated and at 3th, 6th, 12th month after activation. Hearing thresholds and speech perception were also tested at least three months after the activation of the Bonebridge under three conditions: unaided, unilateral Bonebridge, and bilateral bone conduction hearing devices (Bonebridge plus contralateral ADHEAR). The international hearing aid assessment questionnaire (IOI-HA) and Glasgow children's benefit questionnaire were used to evaluate the subjective benefits of the patients. SPSS 21.0 software was used for statistical analysis. Results: Among these 32 patients, nine were conducted Bonebridge implantation surgery before auricle reconstruction, six were simultaneously with auricle reconstruction and 17 were implanted after auricle reconstruction surgery. Compared with unaided, the mean hearing thresholds (0.5, 1, 2, and 4 kHz) and speech perception following unilateral BCHD and bilateral BCHD attachment were improved significantly (P<0.05 each). The speech perceptin in noise of bilateral BCHD was better than unilateral (P<0.05 each). The modified questionnaire revealed high levels of patient satisfaction following use of both unilateral and bilateral devices. Conclusions: Individulized surgical procedures involving auricle reconstruction and Bonebridge implantation are safe and effective for patients with bilateral microtia-atresia, solving both appearance and hearing problems. Speech perception in noise is better following bilateral BCHD than unilateral BCHD attachment.

[Selection of cochlear electrode array implantation lengths and outcomes in patients with bilateral sensorineural hearing loss].

Objective: To perform a comprehensive comparison on the therapeutic effects of unilateral 31.5 mm and 28 mm cochlear implantation (CI) on the post-operative hearing rehabilitation outcomes, including hearing threshold, speech recognition and quality of life, in patients with bilateral sensorineural hearing loss. Methods: A total of 26 patients [12 males, 14 females, aged 19-71 (43±16) years] diagnosed with bilateral severe-to-profound sensorineural hearing loss at Peking Union Medical College Hospital from April 2018 to August 2019 were included. Patients underwent temporal bone high resolution CT (HRCT), based on which the electrode lengths were calculated using OTOPLAN. Eleven and fifteen ears were implanted with MED-EL Flex 31.5 mm and Flex 28 mm electrode arrays respectively, via round window approach under minimally invasive surgery. The patients were followed up regularly for up to 2 years. At each follow-up, aided hearing threshold, speech recognition in quiet and noise, and Nijmegen Cochlear Implantation Questionnaire (NICQ) scores were evaluated and compared. Results: Post-operative hearing thresholds were (46.5±3.4) dB and (48.5±2.2) dB in patients implanted with MED-EL Flex 31.5 mm and Flex 28 mm electrode arrays, respectively, with no statistically significant difference (P=0.074). Both hearing thresholds and speech recognition demonstrated significant post-operative improvement compared with pre-operative results. Hearing thresholds after 1-year post-operation were (32.1±1.2) dB and (32.5±0.9) dB, respectively (P=0.355). Patients implanted with Flex 31.5 mm electrode scored significantly higher at speech recognition under 65 dB sound pressure level (SPL) at most of the follow-ups (All P<0.05). Speech recognition in noise (S/N=10 dB) was also improved in patients implanted with Flex 31.5 mm electrode. All sub-divisions of the NICQ demonstrated significant post-operative improvement, and no significant difference between the 2 groups was observed apart from the"self-confidence"sub-division. Conclusions: Selection of MED-EL Flex 31.5 mm and 28 mm implantation based on pre-operative OTOPLAN evaluation can both bring significant improvements to patients' hearing and quality of life. Flex 31.5 mm electrode can potentially provide better speech recognition within a certain period after surgery.

A common variant rs2272804 in the 5'UTR of RIBC2 inhibits downstream gene expression by creating an upstream open reading frame.

OBJECTIVE: The RIB43A domain with coiled-coils 2 (RIBC2) encodes an uncharacterized vertebrate protein exhibiting similarity with Chlamydomonas protofilament ribbon proteins, required for ciliary motility. To date, no functional variants capable of triggering a change in the expression of RIBC2 have been reported. PATIENTS AND METHODS: The genotypes of rs2272804 in 30 individuals were identified with Sanger sequencing to estimate allele frequencies. Dual-Luciferase and mutagenesis assays were carried out to investigate the impact of rs2272804 on transcriptional and translational levels. The microarray data of 7 types of cancer were obtained from the Gene Expression Omnibus (GEO) to explore the role of rs2272804 in those diseases. RESULTS: In this study, we identified a common variant in the 5'UTR of RIBC2, rs2272804, which can create an upstream open reading frame (uORF) in the 5'UTR significantly inhibiting the expression of its host gene. Using Dual-Luciferase constructs, we found that this variant leads to an 85% reduction in translational efficiency, but only a 20% decrease was observed at the transcriptional level. In terms of population studies, mRNA levels of RIBC2 varied according to their rs2272804 genotypes. The "A" allele homozygotes, which created a uORF, showed the lowest transcriptional levels while the transcriptional activity of the "C" allele homozygotes without an uORF was the highest, consistent with the in-vitro studies. Furthermore, we explored its role in 7 types of cancer and identified RIBC2 as a significantly differentially expressed gene (DEG) in breast cancer (BRCA), ovarian serous cystadenocarcinoma (OV), and kidney renal clear cell carcinoma (KIRC). Finally, we showed that the overexpression of RIBC2 enhanced the expression of TRIM37 and down-regulated TRAF2. TRIM37 is a member of the tripartite motif (TRIM) family involved in developmental patterning and oncogenesis while TRAF2 is associated with the signal transduction from members of the TNF receptor superfamily. CONCLUSIONS: Our reports identified a common variant that exerts a dramatic impact on expression efficiency and provides further functional insight into RIBC2.

[IgG4-associated diseases mainly with auricular symptoms: a case report and literature review].

Summary To analyze the clinical features of IgG4-related diseases mainly with otologic manifestations and investigate diagnosis and treatment of IgG4-related diseases. We report the clinical course and diagnosis and treatment process of a case of IgG4-related disease misdiagnosed as chronic suppurative otitis media. After looking through relevant literatures, we review 22 cases of IgG4-related diseases mainly with otologic manifestations, and summarize their epidemiological characteristics, clinical manifestations, histopathologic features, radiologic features, and diagnostic and therapeutic criteria. IgG4-related diseases mainly with otologic manifestations are usually clinically characterized by atypical symptoms such as otalgia, tinnitus, aural fullness, otorrhea and progressive or fluctuating hearing loss, together with nausea, vomiting, and dizziness. The three central histopathologic features are dense lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis. The exact diagnosis of IgG4-related diseases requires a combination of clinical manifestations, serology, histopathology and radiologic results. Glucocorticoids are currently the first-line approach for IgG4-related diseases. Otologic manifestations involved in IgG4-related diseases are poorly specific, which is likely to result in more misdiagnosis and treatment delay. Current golden standard for diagnosing IgG4-related diseases is the identification of characteristic histopathology. In addition, immunohistochemistry can help clinicians diagnose IgG4-related diseases as early as possible. Otologists should strengthen their understanding of otologic manifestations of IgG4-related diseases. Early diagnosis and treatments are the key factors in prognosis.

[Outcome of cochlear implantation in a patient with Chiari malformation type â who presented with hearing loss].

Summary Chiari malformation type Ⅰ（CMI） is a disorder characterized by tonsilla cerebelli herniating into an underdeveloped posterior cranial fossa, hearing loss is often covered by more striking neurological symptoms. Hearing loss in this syndrome is not specific in terms of gender side, degree, age of onset, and progression. The hearing improvement after posterior fossa decompression is controversial on the basis of literature, while satisfactory result was obtained after cochlear implantation in the patient reported here, who was diagnosed as CMI with hearing loss as the main symptom. Therefore, after ensuring the integrity of the auditory pathway, cochlear implantation may be considered in CMI patients with bilateral severe or profound without other severe neurological symptoms.

[The inhibition of 18ß-sodium glycyrrhetinic acid on thymic stromal lymphopoietin expression in the nasal mucosa of allergic rhinitis rats].

Objective: To explore the effect of 18ß-sodium glycyrrhetinic acid on thymic stromal lymphopoietin (TSLP) in nasal mucosa of allergic rhinitis (AR) rats. Methods: One hundred Wistar rats,half male and half female,were randomly divided into 5 groups by random number table method: control group, AR model group,budesonide group,18ß-sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg groups, with 20 rats in each group. AR animal models were established by ovalbumin (OVA) sensitization in the other four experimental groups. After successful modeling, budesonide and 18ß-sodium glycyrrhetinic acid were given in each group,and the detection time points were 2 weeks and 4 weeks. The distribution of TSLP in rat nasal mucosa was detected by immunohistochemistry,and the expression of TSLP in rat nasal mucosa was determined by Western blot at the protein level. The expression of TSLP-mRNA in rat nasal mucosa was detected and compared by real-time fluorescence quantitative PCR (RT-PCR) at mRNA level. The concentrations of IL-4 and OVA-sIgE in rat serum were measured and compared by ELISA. One-way analysis of variance and the least significant difference method were used for the comparison among groups, LSD t test was used for the comparison between the two groups,and the difference was statistically significant (P<0.05). Results: Immunohistochemistry confirmed existence of TSLP in rat nasal mucosa, especially in epithelial cells,endothelial cells and epithelial cilia. Western blot and RT-PCR suggested that the expression of TSLP and TSLP-mRNA in nasal mucosa of AR model group was significantly higher than that of control group (2 weeks TSLP: 1.795 9±0.131 4 vs 0.990 5±0.164 2, 4 weeks TSLP: 1.809 7±0.253 4 vs 0.870 3±0.124 4; 2 weeks TSLP-mRNA:4.582 9±0.697 7 vs 1.108 7±0.081 1, 4 weeks TSLP-mRNA:4.814 4±0.662 8 vs 1.001 0±0.155 3; all P<0.05). After 2 weeks and 4 weeks of drug intervention,the expression of TSLP and TSLP-mRNA was inhibited in nasal mucosa of budesonide group,18ß-sodium sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg group,which was significantly different from that of AR model group (2 weeks TSLP: (0.897 8±0.081 8)/(1.072 1±0.113 6)/(1.396 6±0.133 9) vs 1.795 9±0.131 4; 4 weeks TSLP: (1.191 0±0.161 3)/(1.141 0±0.152 3)/(1.200 5±0.189 6) vs 1.809 7±0.253 4; 2 weeks TSLP-mRNA: (1.175 6±0.100 9)/(1.254 4±0.078 2)/(2.037 2±0.559 2) vs 4.582 9±0.697 7; 4 weeks TSLP-mRNA: (1.158 3±0.104 3)/(1.224 0±0.034 0)/(1.275 2±0.099 6) vs 4.814 4±0.662 8; all P<0.05), and not significantly different from control group. With the inhibition of TSLP, the concentrations of IL-4 and OVA-sIgE in rat serum were also decreased. Conclusion: 18ß-sodium glycyrrhetinic acid has obvious inhibitory effect on TSLP in nasal mucosa of AR rats, which can control Th2 type immune inflammatory reaction.

[Effects of 18ß-sodium glycyrrhetinic acid on TNF-α expression in rats with allergic rhinitis].

Objective:To observe the effect of 18ß-sodium glycyrrhetinic acid(18ß-SGA) on the expression of TNF-α in nasal mucosa of rats with allergic rhinitis（AR）, and explore the intervention mechanism of 18ß-SGA on AR. Method:One hundred and six SPF-level Wistar rats were randomly divided into control group, AR group, budesonide group, 18ß-SGA low dose group and high dose group. After the AR rat model was constructed by ovalbumin, the rats were given drug intervention and sacrificed after 2 and 4 weeks of intervention. The nasal mucosa of the rats was taken for immunohistochemical staining, RT-qPCR and Western-blotting to localize and quantify the expression of TNF-α. Result:By immunohistochemistry, Western-blotting and RT-PCR, TNF-α was mainly found in the columnar epithelium, vascular endothelium, glandular and some inflammatory cytoplasm of nasal mucosa. And the expression of TNF-α in the nasal mucosa of AR rats was significantly increased than the normal group at the protein and mRNA levels (P<0.01). After intervention with different doses of 18ß-SGA, the expression of TNF-α was significantly decreased (P<0.01), especially after 4 weeks of 18ß-SGA low dose group(P<0.01). Conclusion:Different doses of 18ß-SGA have therapeutic effects on AR, and its mechanism of action may be related to the inhibition of TNF-α expression.

Improved anchoring nails: design and analysis of resistance ability : Tensile test and finite element analysis (FEA) of improved anchoring nails used in temporomandibular joint (TMJ) disc anchor.

BACKGROUND: Anchorage is one of the most important treatments for severe temporomandibular joint disorder (TMD). Anchoring nails have shown great success in clinical trials; however, they can break under pressure and are difficult to remove. In this study, we aimed to evaluate an improved anchoring nail and its mechanical stability. METHODS: The experiment consisted of two parts: a tensile test and finite element analysis (FEA). First, traditional and improved anchoring nails were implanted into the condylar cortical bone and their tensile strength was measured using a tension meter. Second, a three-dimensional finite element model of the condyles with implants was established and FEA was performed with forces from three different directions. RESULTS: The FEA results showed that the total force of the traditional and improved anchoring nails is 48.2 N and 200 N, respectively. The mean (±s.d.) maximum tensile strength of the traditional anchoring nail with a 3-0 suture was 27.53 ± 5.47 N. For the improved anchoring nail with a 3-0 suture it was 25.89 ± 2.64 N and with a 2-0 suture it was above 50 N. The tensile strengths of the traditional and improved anchoring nails with a 3-0 suture was significantly different (P = 0.033-< 0.05). Furthermore, the difference between the traditional anchoring nail with a 3-0 suture and the improved anchoring nail with a 2-0 suture was also significantly different (P = 0.000-< 0.01). CONCLUSION: The improved anchoring nail, especially when combined with a 2-0 suture, showed better resistance ability compared with the traditional anchoring nail.

[The effect of berberine on ameliorating chronic inflammatory pain and depression].

Objective: To explore the effect of berberine on chronic inflammatory pain and the comorbid depression and the associated mechanisms. Methods: Forty healthy male ICR mice (2 months, 25-30 g) were used in the present study. The chronic inflammatory pain was induced by intraplantar injection of complete freund's adjuvant (CFA) to the hind paws. All animals were divided into 4 groups (n=10 for each group) according to random number table: the saline group (group A), the chronic pain group (group B), the saline+ berberine group (group C) and the chronic pain+ berberine group (group D). The baseline data of pain and depressive performance were measured on the day before any drug treatment.On d1, mice of B and D groups received intraplantar injections of 50 µl CFA emulsion (1∶1 diluted with saline); mice of A and C groups received intraplantar injections of the same volume of saline. During d15-d21, mice of C and D groups received intraperitoneal injections of berberine (50 mg/kg, daily for 7 days); mice of A and B groups received the equal volume of saline. The Hargreaves tests and the Von Frey tests were conducted before the injection of CFA and on d7, d14, d17 and d21 to measure the thermal and mechanical pain thresholds. The forced swimming tests and novelty-suppressed feeding tests were performed before the injection of CFA and on d21 to measure the depressive performance. After the behavioral tests, the levels of inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) at the lumbar (L4-L5) spinal cord were examined by enzyme-linked immunosorbent assay(ELISA). The mRNA level of chemokine C-C motif ligand 2 (CCL2) in the lumbar spinal cord was examined by quantitative real-time polymerase chain reaction(qRT-PCR). Results: Compared with group A, the thermal withdrawal latency of group B mice on d7, d14, d17, d21 was declined[(3.40±0.67)s vs (10.55±1.58)s, (7.49±1.04)s vs (11.47±1.92)s, (6.46±0.56)s vs (11.60±1.86)s, (6.04±0.54)s vs (10.33±1.59)s, all P<0.01], and the mechanical threshold was also decreased[(0.15±0.03)g vs (0.78±0.24)g, (0.23±0.12)g vs (0.60±0.16)g, (0.30±0.12)g vs (0.72±0.25)g, (0.40±0.00)g vs (0.72±0.19)g, all P<0.01], on d21 the immobility time was increased[(161.60±35.79)s vs (88.92±53.24)s , P<0.05]and the time of feeding latency was decreased[(227.40±57.5)s vs (77.25±26.45)s, P<0.01], suggesting that CFA could induce hyperalgesia and depression. After berberine treatment (daily for 7 days), compared with group B, the thermal withdrawal latency of group D mice was increased[(9.99±2.68)s vs (6.04±0.54)s, P<0.01], the mechanical threshold was elevated[(0.80±0.21)g vs (0.40±0.00)g, P<0.01], the immobility time was decreased[(92.97±44.31)s vs (161.60±35.79)s, P<0.05], and the feeding latency was declined[(105.00±50.00)s vs (227.40±57.5)s, P<0.01]. Compared with group A, the concentrations of spinal IL-1ß, IL-6 and TNF-α in group B were increased[(29.90±4.87)pg/ml vs (21.00±5.46)pg/ml, (131.10±26.12)pg/ml vs (60.68±23.47)pg/ml, (21.54±4.93)pg/ml vs (11.39±3.66) pg/ml , all P<0.01], the mRNA level of CCL2 was upregulated[(2.21±0.60) vs (1.00±0.37), P<0.01]. After berberine treatment (daily for 7 days), compared with group B, the concentrations of IL-1ß, IL-6 and TNF-α in group D were decreased[(19.44±4.83)pg/ml vs (29.90±4.87) pg/ml , (57.82±32.28)pg/ml vs (131.10±26.12)pg/ml , (9.29±2.46)pg/ml vs (21.54±4.93) pg/ml, all P<0.01], the mRNA level of CCL2 was downregulated[(1.33±0.40)vs (2.21±0.60), P<0.05]. Conclusion: Berberine can reverse chronic inflammatory pain induced by CFA and alleviated the comorbid depression. Its anti-nociceptive and anti-depressive effects may associate with downregulation of the spinal levels of the inflammatory cytokines and mRNA transcription of CCL2.