AIM: To investigate the effects of transient receptor potential channel 6 (TRPC6) on the proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) induced by IL-1β.METHODS: The mRNA expression of TRPC6 in synovial tissues from RA or OA patients was studied by RT-qPCR.RA-FLS were cultured by enzyme digestion and tissue adhesion methods.The method of flow cytometry was applied to identify the RA-FLS.RA-FLS were treated with different concentrations (0, 0.25, 0.5, 1, 2, 4, 8 and 16 μg/L) of IL-1β for 36 h.The cell viability was examined by CCK-8 assay.RA-FLS were incubated with IL-1β (16 μg/L) for different time (12, 24, 36, 48, 60 and 72 h), and the cell viability was measured by CCK-8 assay.The interference efficiency of TRPC6-siRNA was determined by RT-qPCR and Western blotting.After incubation in the presence or absence of IL-1β medium, the cell viability, the percentage of EdU-positive cells and the percentage of (G2/M+S) phase were measured by CCK-8 assay, EdU labeling assay and flow cytometry, respectively.RESULTS: The mRNA expression of TRPC6 was found in synovial tissue with higher levels in RA patients than that in OA patients.TRPC6-siRNA significantly decreased the mRNA and protein expression of TRPC6 (P<0.05).When RA-FLS were treated with IL-1β, the proliferation of RA-FLS was increased (P<0.05).The differences of the cell viability, the percentage of EdU-positive cells and the (G2/M+S) phase percentage between TRPC6-siRNA group and blank control group or NC-siRNA group were significant, in the presence of IL-1β (P<0.05).However, they were not significant in the absence of IL-1β.CONCLUSION: TRPC6 is involved in the proliferation of RA-FLS induced by IL-1β.Silencing of TRPC6 gene inhibits the growth of RA-FLS induced by IL-1β.

BACKGROUND:Triggering receptor expressed on myeloid cel s 2 (TREM-2) is highly expressed throughout the synovial tissue in active rheumatoid arthritis patients, but the role of TREM-2 in the pathogenesis of rheumatoid arthritis stil remains unclear.
OBJECTIVE:To explore the TREM-2 expression in the synovial tissue of col agen type II-induced arthritis rats.
METHODS:The col agen-induced arthritis models were established in rats. The activity indicators and pathological changes of arthritis synovial were dynamical y observed. The mRNA levels of TREM-2, tumor necrosis factor-α, interleukin-1β, and interleukin-10 were detected in synovial tissue of rats by RT-PCR. The protein expression and location of TREM-2 were measured with western blot assay and immunohistochemistry, respectively.
RESULTS AND CONCLUSION:At day 13 after immunization, the paws of model rats appeared red and swel ing, the arthritis index scores were increased (P<0.01). At day 19-25 after immunization, the inflammation reached the peak. Hematoxylin-eosin staining showed that, the synovium of col agen-induced arthritis rats were proliferated and were infiltrated by inflammatory cel s, cartilage was destroyed. Compared with the control group, the expression of TREM-2 mRNA and protein, the mRNA levels of tumor necrosis factor-αand interleukin-1βin synovial tissue of the model rats were significantly increased (P<0.05 or P<0.01), while interleukin-10 mRNA expression was significantly decreased (P<0.05). Experimental findings indicate that, TREM-2 is a crucial inflammatory regulator and the increasing expression of TREM-2 plays an important role in the pathogenesis of col agen-induced arthritis.

Objective To investigate the influencing factors of pain and the changes of vital signs in newborn infants. Methods Forty two newborn infants were rated by the behavioral scale of acute pain in newborn infants. The scores of pain were compared among infants with different gender,gestational age,birth weight,birth age,type of puncture and whether by vaginal birth or not. At the same time,the respiration rate,heart rate,blood pressure and oxygen saturation (SO2)were dynami-cally recorded by the multi-function monitor in the process of puncture. Results The average score of pain was 7.6. There was no significant difference among newborn infants with different gender,gestational age,birth weight and type of puncture(P> 0.05),while significant differences among infants with different birth age and whether by vaginal birth or not (P=0.015 and 0.043 respectively). In the process of puncture,the SO2 was significantly decreased,while the respiration rate,heart rate,sys-tolic and diastolic blood pressure were significantly increased. Conclusions Pain is prevalent in newborn infants and accom-panied by obvious changes of vital signs. The means of childbirth and birth age have significant influence on the neonatal pain. It is suggested to pay close attention to the neonatal pain and take effective interventions.

Objective To investigate the influences of pain on early neonatal neurobehavioral development Methods 65 newborn infants admitted to the Neonatal Intensive Care Unit( NICU )of our hospital from October,2009 to March,2010 were randomly chosen as the objects of this study.In light of Neonatal Behavioral Neurological Assessment( NBNA) revised by Professor Bao Xiulan,examinations were carried out before and after pain stimulation,and a statistical analysis of the results of the examinations was conducted.Results The total scores of NBNA before and after the pain stimulation were (36.49±1.73) vs.(34.80±1.79) respectively,demonstrating a significant difference.Specifically,after the pain stimulation,the scores of behavioral ability and active muscle tension decreased,with a very significant difference.However,there was no significant difference in terms of the scores of passive muscle tone,primitive reflexes and common reactions.Conclusions Neonatal pain exerts influences on early neurobehavioral development,particularly on behavioral ability and active muscle tension.The training of neonatal health care professionals in the management of and the intervention in neonatal pain should be strengthened in order to decrease the adverse effects of pain on neonates.

[Summary] All patients with cholesterol side-chain cleavage enzyme ( P450scc) deficiency that have been reported presented with early adrenal failure. Here we described a 35-year-old male presented with infertility as the only initial presenting complaint. He had received two separate surgeries to remove bilateral testicular masses. We reevaluated the resected tumors and found testicular adrenal rest tumor ( TART) pathology in the resected tumor. We profiled steroid hormones and found significantly elevated ACTH. CT scan revealed bilateral adrenal hyperplasia. Mutation screening identified compound heterozygous mutations (R353W and P432L) in the P450scc encoding gene (CYP11A1). The patient was finally diagnosed as congenital adrenal hyperplasia.

Objective:To investigate the effect of Guilu Erxian Jiao (GEJ) on the negative feedback function of hypothalamic-pituitary-adrenal (HPA) axis and its possible mechanism in rats with post-traumatic stress disorder(PTSD).Methods:The PTSD rat model was established using single prolonged stress (SPS). Ninety six SD rats were randomly divided into control group (control), model group (SPS), GEJ group (GEJ) and paroxetine group (PRX) according to the random number table with 24 rats in each group. Except the control group, the rats in the other groups were constructed using the PTSD model. On the 8th day after the establishment of the model, the rats of the GEJ group (3.6 g/kg) and the PRX group (10 mg/kg) were respectively given the drug by gavage for 21 days. The rats in control group and SPS group were given the same amount of distilled water once a day for 21 days. After continuous administration for 21 days, 12 rats were randomly selected from each group for the dexamethasone suppression test (DST), then 6 rats were selected for the RT-PCR, and the remaining 6 rats were used for immunohistochemistry. The contents of plasma adrenocorticotrophic hormone (ACTH) were measured by Elisa. The expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), adrenocorticotropic hormone releasing factor Ⅰ receptor (CRF1R) and adrenocorticotropic hormone releasing factor Ⅱ receptor (CRF2R) were detected by RT-PCR and immunohistochemistry.Results:(1) In DST, plasma ACTH level in SPS group was significantly lower than that in control group((145.89±19.41)μg/L, (203.59±35.78)μg/L, t=3.16, P<0.01), and that in the PRX group and GEJ group were significantly higher than that in SPS group((218.47±37.55)μg/L, t=3.98, P<0.01; (205.33±66.54)μg/L, t=3.26, P<0.01). (2) RT-PCR results showed that, in hippocampus, the GR mRNA and MR mRNA expressions in SPS group were significantly higher than those in control group((1.29±0.02), (1.00±0.06), t=6.88, P<0.01; (1.38±0.02), (1.00±0.05), t=7.97, P<0.01), and that in the GEJ group significantly decreased comparing to SPS group((0.96±0.07), t=7.87, P<0.01; (0.86±0.13), t=11.03, P<0.01). (3) Immunohistochemical results showed that, in hippocampus, the positive cell expressions of GR and MR in the SPS group were significantly higher than those in control group((84.33±12.82), (69.33±8.19), t=2.50, P<0.05; (77.33±6.65), (56.33±11.79), t=2.25, P<0.05), and that in the GEJ group significantly were lower than SPS group((68.33±4.55), t=2.67, P<0.05; (59.50±4.18), t=2.25, P<0.05). In amygdala, the positive cells expression of GR, MR and CRF1R in the SPS group significantly decreased compared with the control group((62.67±6.89), (77.17±10.70), t=3.10, P<0.05; (60.50±11.66), (91.83±15.63), t=3.43, P<0.05; (54.50±19.96), (88.17±22.43), t=2.31, P<0.05); and that in GEJ group significantly increased compared with the SPS group((74.33±5.85), t=2.11, P<0.05; (83.67±12.55), t=2.53, P<0.05; (88.67±16.28), t=2.35, P<0.05). Conclusion:GEJ can inhibit the enhanced HPA axis negative feedback function induced by SPS, which may be related to regulating expression of GR, MR and CRF1R in the hippocampus and amygdala.

Congenital generalized lipodystrophy type 1 (CGL1) is an autosomal recessive genetic disease caused by mutations in AGPAT2 gene. The main clinical mainifestations include body subcutaneous fat loss, muscle hypertrophy, obvious subcutaneous veins, pseudoacromegaly, hirsutism, and acanthosis nigricans. What′s more, CGL1 is always accompanied by metabolic diseases. Therefore, it is easily misdiagnosed as metabolic syndrome, type 2 diabetes, polycystic ovary syndrome, acromegaly, or Cushing′s syndrome. Meanwhile, it is difficult to distinguish it from partial lipoatrophy syndrome. In this article, we present clinical and molecular characteristics of a patient with CGL1 and review mutations reported in literature to replenish current knowledge about this orphan disease.

Objective:To analyze the distribution characteristics of special types of diabetes in China, in order to provide a theoretical basis for the diagnosis and treatment of special types of diabetes.Methods:Pubmed, CNKI, and WanFang Data were searched for the case reports and clinical studies of special types of diabetes in China from 2011 to 2021. After independent literature screening by 2 researchers according to the inclusion and exclusion criteria, diseases and the number of corresponding cases included were extracted for statistics. The etiological composition and disease characteristics of three subtypes of special type diabetes were analyzed.Results:A total of 613 articles(7 377 patients)were included and roughly divided into eight subtypes of special type diabetes according to etiological classification for disease composition analysis. The results by ratio in descending order were as follows: mono-genetic gene defects in islet β-cell function, pancreatogenic diabetes, diabetes induced by drugs or chemicals, endocrine disease, mono-genetic gene defects in insulin action, other genetic syndromes associated with diabetes, infection, and uncommon immune-mediated diabetes. The disease composition of the three subtypes of special types of diabetes that we focused on were mono-genetic gene defects in islet β-cell function(50.21%), pancreatogenic diabetes(35.65%), and mono-genetic gene defects in insulin action(1.56%). The composition analysis of the special types of diabetes in each subtype showed that neonatal diabetes mellitus(NDM, n=1 749, 23.71%)and maturity onset diabetes in young(MODY, n=1 554, 21.07%)accounted for the largest proportions. According to the composition analysis of each subtype of MODY patients, the top three subtypes were MODY2(50.89%), MODY3(16.03%), and MODYX(8.91%). In addition, taking MODY as an example, patients with de novo mutations(DNMs)and(or)new mutation sites were summarized and analyzed. The results revealed 31 MODY patients with DNMs(1.99%) and 339 MODY patients with new mutation sites(21.81%). Conclusions:According to the literature analysis, NDM and MODY represent the largest proportion of patients with special type diabetes in China. MODY2 patients make up the largest proportion of MODY patients. In addition, diabetic patients carrying DNMs and(or)new mutation sites should be taken seriously.