Objective:To assess iodine nutritional status and the prevalence of thyroid dysfunction in Kunming, Yunnan Province, along with correlation and risk factors between thyroid dysfunction and urinary iodine levels.Methods:This cross-sectional study was conducted from January 2014 to July 2016 using a multi-stage, stratified cluster sampling method. A total of 2 650 residents of Kunming, Yunnan Province, who met the inclusion criteria were selected. Data on participants′ demographics, physical measurements, and laboratory tests were collected through questionnaire and clinical assessments which led to 1 463 subjects in the final analysis considering missing data. Statistical analysis were performed using SPSS 26.0, while R Studio was used to model the nonlinear relationship between urinary iodine levels and the risk of thyroid dysfunction.Results:(1) Among 2 650 subjects, 755(28.5%) were diagnosed with thyroid dysfunction, with incidence rates of clinical hyperthyroidism(0.83%), subclinical hyperthyroidism(0.38%), clinical hypothyroidism(1.36%), subclinical hypothyroidism(17.66%), and isolated thyroid antibody positive(13.85%). The median urinary iodine concentration was 177.49(123.59, 251.85) μg/L, indicating adequate iodine nutritional. (2)Among the 1 463 subjects analyzed, significant differences in urinary iodine were found between healthy individual group and abnormal TSH group or abnormal TSH group and thyroid antibody positive group( H=-83.437, P=0.003; H=107.489, P=0.003). Logistic regression revealed that rural residents had a lower risk of thyroid dysfunction than urban residents( OR=0.429, 95% CI 0.256-0.717, P=0.001). Risk of thyroid disease increased with age, and TSH, thyroid peroxidase antibody(TPOAb), thyroglobulin antibody(TgAb), and urinary iodine levels were identified as significant risk factors, with a U-shaped relationship between urinary iodine levels and thyroid dysfunction. Conclusions:The prevalence of thyroid dysfunction in Kunming is comparable to the national average. The relationship between urinary iodine concentration and thyroid dysfunction follows a U-shaped curve. Factors including region, age, TSH, TPOAb, TgAb, and urinary iodine concentration are associated with thyroid dysfunction.

Objective Based on the transcriptome data of Scolopendra subspinipes mutilans L.Koch,SSR primers were designed and developed to evaluate the genetic diversity and analyze the population structure of the germplasm resources of S.mutilans,which can provide a theoretical basis for the development and utilization of the germplasm resources of S.mutilans.Methods We collected 301 samples of S.mutilans from major production areas,and analyzed the population genetic diversity and population structure of the germplasm resources of S.mutilans using 18 pairs of highly polymorphic SSR primers after screening.Results A total of 142 alleles were amplified by 18 primer pairs across all samples,with an average of 7.89 alleles amplified per locus.The mean of observed heterozygosity(HO)of the 18 populations was 0.39,the mean of expected heterozygosity(HE)was 0.46,the mean of polymorphism information content(PIC)was 0.41,the mean of Nei's gene diversity index(H)was 0.46,and the mean of Shannon information index(I)was 0.81.The results showed that the wild resources of S.mutilans collected in this study had a high level of genetic diversity,Four populations in Anhui and Zhejiang had higher genetic diversity than populations in Hubei.Molecular analysis of variance(AMOVA)of the population showed that most of the genetic variation in the materials of this study mainly occurred within populations.The STRUCTURE analysis of germplasm resources showed that all germplasm could be divided into four populations.Conclusion This study showed that the natural population of S.mutilans possesses high genetic diversity with high genetic variation and is better adapted to changes in the environment.Our results provided a research basis for the rational utilization of the germplasm resources of S.mutilans and the selection and breeding of superior varieties.

Objective Based on the transcriptome data of Scolopendra subspinipes mutilans L.Koch,SSR primers were designed and developed to evaluate the genetic diversity and analyze the population structure of the germplasm resources of S.mutilans,which can provide a theoretical basis for the development and utilization of the germplasm resources of S.mutilans.Methods We collected 301 samples of S.mutilans from major production areas,and analyzed the population genetic diversity and population structure of the germplasm resources of S.mutilans using 18 pairs of highly polymorphic SSR primers after screening.Results A total of 142 alleles were amplified by 18 primer pairs across all samples,with an average of 7.89 alleles amplified per locus.The mean of observed heterozygosity(HO)of the 18 populations was 0.39,the mean of expected heterozygosity(HE)was 0.46,the mean of polymorphism information content(PIC)was 0.41,the mean of Nei's gene diversity index(H)was 0.46,and the mean of Shannon information index(I)was 0.81.The results showed that the wild resources of S.mutilans collected in this study had a high level of genetic diversity,Four populations in Anhui and Zhejiang had higher genetic diversity than populations in Hubei.Molecular analysis of variance(AMOVA)of the population showed that most of the genetic variation in the materials of this study mainly occurred within populations.The STRUCTURE analysis of germplasm resources showed that all germplasm could be divided into four populations.Conclusion This study showed that the natural population of S.mutilans possesses high genetic diversity with high genetic variation and is better adapted to changes in the environment.Our results provided a research basis for the rational utilization of the germplasm resources of S.mutilans and the selection and breeding of superior varieties.

Objective:To assess iodine nutritional status and the prevalence of thyroid dysfunction in Kunming, Yunnan Province, along with correlation and risk factors between thyroid dysfunction and urinary iodine levels.Methods:This cross-sectional study was conducted from January 2014 to July 2016 using a multi-stage, stratified cluster sampling method. A total of 2 650 residents of Kunming, Yunnan Province, who met the inclusion criteria were selected. Data on participants′ demographics, physical measurements, and laboratory tests were collected through questionnaire and clinical assessments which led to 1 463 subjects in the final analysis considering missing data. Statistical analysis were performed using SPSS 26.0, while R Studio was used to model the nonlinear relationship between urinary iodine levels and the risk of thyroid dysfunction.Results:(1) Among 2 650 subjects, 755(28.5%) were diagnosed with thyroid dysfunction, with incidence rates of clinical hyperthyroidism(0.83%), subclinical hyperthyroidism(0.38%), clinical hypothyroidism(1.36%), subclinical hypothyroidism(17.66%), and isolated thyroid antibody positive(13.85%). The median urinary iodine concentration was 177.49(123.59, 251.85) μg/L, indicating adequate iodine nutritional. (2)Among the 1 463 subjects analyzed, significant differences in urinary iodine were found between healthy individual group and abnormal TSH group or abnormal TSH group and thyroid antibody positive group( H=-83.437, P=0.003; H=107.489, P=0.003). Logistic regression revealed that rural residents had a lower risk of thyroid dysfunction than urban residents( OR=0.429, 95% CI 0.256-0.717, P=0.001). Risk of thyroid disease increased with age, and TSH, thyroid peroxidase antibody(TPOAb), thyroglobulin antibody(TgAb), and urinary iodine levels were identified as significant risk factors, with a U-shaped relationship between urinary iodine levels and thyroid dysfunction. Conclusions:The prevalence of thyroid dysfunction in Kunming is comparable to the national average. The relationship between urinary iodine concentration and thyroid dysfunction follows a U-shaped curve. Factors including region, age, TSH, TPOAb, TgAb, and urinary iodine concentration are associated with thyroid dysfunction.

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

Objective: Brain and muscle ARNT-like protein 1 (BMAL1) is a core component of hepatocyte molecular clock and plays an important role in the regulation of other related rhythmic genes in the body through a transcriptional-translational feedback loop in molecular circadian oscillations. Therefore, the aim of this study was to investigate the role of BMAL1 in the rat periodontitis-induced liver injury. Methods: Twelve male Wistar rats were divided into the control group and the periodontitis group according to the random number table method. The rats in the control group were untreated. The periodontitis models were established by ligating the necks of the bilateral maxillary first molars in the periodontitis group rats. After 8 weeks, periodontal clinical indexes of rats in both groups were examined and executed. Micro-CT scans of the maxilla were performed and levels of the alveolar bone resorption were analyzed. Pathological changes in periodontal and liver tissue of rats in two groups were detected by HE and oil red O staining. Biochemical kits were used to detect glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), total cholesterol (TC) and triglycerides (TG) in serum. The gene and protein expression levels of BMAL1, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) in liver tissue were measured by real time fluorescent quantitative-PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) assays. Apoptosis was detected in liver tissues by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) kit staining. Results: The results of HE staining of maxillary first molars and micro-CT results of maxillary bones showed that alveolar bone resorption was significant in the periodontitis group of rats. The liver histopathology results showed infiltrated inflammatory cells in the liver tissue, disorganized liver cords and a large number of lipid droplets formed in the hepatocytes of the periodontitis group compared with the control group. The results of serum biochemical assay showed that the levels of GOT [(62.77±2.59) U/L], GPT [(47.54±1.04) U/L], TC [(3.19±0.23) mmol/L] and TG [(1.11±0.09) mmol/L] in the serum of rats with periodontitis were significantly higher than that in the control group respectively [GOT: (38.66±2.47) U/L, GPT: (31.48±1.57) U/L, TC: (1.60±0.05) mmol/L and TG: (0.61±0.09) mmol/L](P=0.003, P=0.001, P=0.002, P=0.038). qRT-PCR results showed that the mRNA expression level of BMAL1 was significantly decreased in liver tissue of the periodontitis group [(0.60±0.04)%] compared to the control group [(1.01±0.07)%] (t=4.80, P=0.009), while the mRNA expression levels of NF-κB and TNF-α [(1.62±0.12)%, (2.69±0.16)%] were significantly increased compared to the control group [(1.00±0.03)%, (1.03±0.16)%] (P=0.008, P=0.002); IHC results showed that the protein expression level of BMAL1 in liver tissue of the periodontitis group (averaged optical density, AOD) (11.58±2.15) was down-regulated compared to the control group (AOD) (22.66±1.67) (P=0.015), while NF-κB and TNF-α (AOD) (31.77±2.69, 24.31±2.32) were up-regulated compared to the control group (AOD) (19.40±1.82, 11.92±0.94) (P=0.019, P=0.008). WB results showed that the protein expression level of BMAL1 in liver tissue was down-regulated in the periodontitis group [(0.63±0.10)%] compared to the control group [(1.00±0.06)%] (t=3.19, P=0.033), while NF-κB and TNF-α [(1.61±0.12)%, (2.82±0.23)%] were up-regulated compared to the control group [(1.00±0.12)%, (1.00±0.11)%] (P=0.022, P=0.002). TUNEL staining showed increased apoptotic cells in the liver tissue of the periodontitis group of rats compared to the control group. Conclusions: Periodontitis may induce liver injury by down-regulating the BMAL1 expression levels in liver tissue, which in turn activates NF-κB signaling molecules, leading to the elevated levels of inflammation and apoptosis in rat liver.
Animals ; Male ; Rats ; Alanine Transaminase/metabolism* ; ARNTL Transcription Factors/metabolism* ; Aspartate Aminotransferases/metabolism* ; Biotin/metabolism* ; Bone Resorption ; Brain ; Chemical and Drug Induced Liver Injury, Chronic ; Cholesterol ; DNA Nucleotidylexotransferase/metabolism* ; Muscles/metabolism* ; NF-kappa B/metabolism* ; Periodontitis ; Rats, Wistar ; RNA, Messenger/metabolism* ; Triglycerides ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.