Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

Objective:To evaluate the clinical efficacy of methylation sensitive-high resolution melting curve (MS-HRM) detection of IFN-induced protein 44-like (IFI44L) gene methylation in the diagnosis of systemic lupus erythematosus (SLE), as well as the relationship between IFI44L gene markers and the early onset of SLE.Methods:From February 2020 to September 2022, the MS-HRM was used to detect the methylation level of the IFI44L gene in peripheral blood mononuclear cells of 602 SLE patients and 524 other autoimmune disease patients (excluding SLE) from Beijing Peking Union Medical College Hospital, Guangdong Provincial People′s Hospital, and Shenzhen People′s Hospital, totaling 1 126 patients. Compared with the 2012 SLICC criteria, the suspected cases were followed up for 6 months until the onset and clinical diagnosis of SLE were confirmed. The measurement data of normal distribution were expressed as mean±SD, and the consistency analysis was performed using the Kappa consistency test. The clinical diagnostic efficacy indicators were calculated using the receiver operating characteristic (ROC) curve. Results:RR (95% CI) of early suspected cases was 17.06 (9.43, 30.82). The results of IFI44L gene methylation level were in good agreement with the 2012 SLICC criteria, and the sensitivity, specificity and total coincidence rate were 90.53%, 92.56% and 91.47%, respectively. The Kappa value (95% CI) was 0.829(0.796, 0.862) ( P<0.001). The diagnostic efficiency of IFI44L gene methylation level ( Kappa value 0.817) was superior to anti-nuclear antibody, anti-SM antibody and anti-dsDNA antibody ( Kappa value 0.418, 0.216 and 0.440, respectively). The Kappa values (95% CI) of methylation between MS-HRM and pyrosequencing was 0.861(0.806, 0.916), P<0.001. Conclusion:The hypomethylation of IFI44L gene methylation level detected by MS-HRM is closely related to the occurrence and development of SLE, and its diagnostic performance is better than that of three autoantibodies in SLE diagnosis, which can be used for the early diagnosis of SLE.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

Microgravity-induced cardiac remodeling presents a substantial challenge that constrains the advancements in the international space industry,which mainly manifests as alterations in the morphology,structure,and function of the heart.This paper analyzed the core pathogenesis and treatment of microgravity-induced cardiac remodeling based on the theory of"yang transforming qi and yin forming shape"in Huangdi Neijing."Yang transforming qi"reflects the changes in cardiac function,whereas"yin forming shape"reflects the changes in cardiac morphology and structure.Based on the basic and clinical research of space cardiac dysfunctions,the core pathogenesis of microgravity-induced cardiac remodeling is the insufficiency of"yang transforming qi",accompanied by yin excess and yang deficiency due to excessive"yin forming shape"in the early stage,which evolves into deficiency of both yin and yang in the late stage.Thus,this paper specifically refined the treatment methods and corresponding formulas,including warming viscera yang to transform qi,draining yin blood to restore yang qi,and consolidating yin and yang to nourish primal energy.These insights provide systematic theoretical support and conceptual inspiration for the traditional Chinese medicine treatment of microgravity-induced cardiac remodeling.

Objective:To compare the significantly differentially expressed proteins in peripheral blood mononuclear cells between patients with different types of depressive disorders and normal participants and explore objective biomarkers with diagnostic significance.Methods:From March to May 2024, peripheral blood samples were collected from bipolar depression (BP), simple depression (DEP), persistent depressive disorder (PDD), and normal participants (NP) at the outpatient department of the Mental Health Center of Ningxia Medical University General Hospital. Using data-independent acquisition (DIA) quantitative proteomics technology, differentially expressed proteins were identified in the peripheral blood of patients with different types of depressive disorders and normal participants, conducting bioinformatics analysis to obtain candidate objective biomarkers, and finally identifying common and unique objective biomarkers for different types of depressive disorders. Data analysis was conducted using R software (version 4.0) and SPSS 27.0 software.Results:A total of 167 differentially expressed proteins were screened between BP and NP, 30 differentially expressed proteins were screened between DEP and NP, and 14 differentially expressed proteins were screened between PDD and NP.The differential proteins unique to the BP group were ARPC4 SPARC、MTPN、SNCA、YWHAH、MIF、COTL1, the differentially expressed proteins unique to the DEP group were RBBP9 APOF、S100A6, and the unique differential proteins in the PDD group were APOA5 CA1、IGLV3-25、APOC2.Conclusion:The objective biomarkers and signaling pathways obtained using DIA quantitative proteomics technology are of great significance for revealing the biological basis and diagnosing accurately of different types of depressive disorders.

Objective:To compare the significantly differentially expressed proteins in peripheral blood mononuclear cells between patients with different types of depressive disorders and normal participants and explore objective biomarkers with diagnostic significance.Methods:From March to May 2024, peripheral blood samples were collected from bipolar depression (BP), simple depression (DEP), persistent depressive disorder (PDD), and normal participants (NP) at the outpatient department of the Mental Health Center of Ningxia Medical University General Hospital. Using data-independent acquisition (DIA) quantitative proteomics technology, differentially expressed proteins were identified in the peripheral blood of patients with different types of depressive disorders and normal participants, conducting bioinformatics analysis to obtain candidate objective biomarkers, and finally identifying common and unique objective biomarkers for different types of depressive disorders. Data analysis was conducted using R software (version 4.0) and SPSS 27.0 software.Results:A total of 167 differentially expressed proteins were screened between BP and NP, 30 differentially expressed proteins were screened between DEP and NP, and 14 differentially expressed proteins were screened between PDD and NP.The differential proteins unique to the BP group were ARPC4 SPARC、MTPN、SNCA、YWHAH、MIF、COTL1, the differentially expressed proteins unique to the DEP group were RBBP9 APOF、S100A6, and the unique differential proteins in the PDD group were APOA5 CA1、IGLV3-25、APOC2.Conclusion:The objective biomarkers and signaling pathways obtained using DIA quantitative proteomics technology are of great significance for revealing the biological basis and diagnosing accurately of different types of depressive disorders.

Microgravity-induced cardiac remodeling presents a substantial challenge that constrains the advancements in the international space industry,which mainly manifests as alterations in the morphology,structure,and function of the heart.This paper analyzed the core pathogenesis and treatment of microgravity-induced cardiac remodeling based on the theory of"yang transforming qi and yin forming shape"in Huangdi Neijing."Yang transforming qi"reflects the changes in cardiac function,whereas"yin forming shape"reflects the changes in cardiac morphology and structure.Based on the basic and clinical research of space cardiac dysfunctions,the core pathogenesis of microgravity-induced cardiac remodeling is the insufficiency of"yang transforming qi",accompanied by yin excess and yang deficiency due to excessive"yin forming shape"in the early stage,which evolves into deficiency of both yin and yang in the late stage.Thus,this paper specifically refined the treatment methods and corresponding formulas,including warming viscera yang to transform qi,draining yin blood to restore yang qi,and consolidating yin and yang to nourish primal energy.These insights provide systematic theoretical support and conceptual inspiration for the traditional Chinese medicine treatment of microgravity-induced cardiac remodeling.

Objective:To evaluate the clinical efficacy of methylation sensitive-high resolution melting curve (MS-HRM) detection of IFN-induced protein 44-like (IFI44L) gene methylation in the diagnosis of systemic lupus erythematosus (SLE), as well as the relationship between IFI44L gene markers and the early onset of SLE.Methods:From February 2020 to September 2022, the MS-HRM was used to detect the methylation level of the IFI44L gene in peripheral blood mononuclear cells of 602 SLE patients and 524 other autoimmune disease patients (excluding SLE) from Beijing Peking Union Medical College Hospital, Guangdong Provincial People′s Hospital, and Shenzhen People′s Hospital, totaling 1 126 patients. Compared with the 2012 SLICC criteria, the suspected cases were followed up for 6 months until the onset and clinical diagnosis of SLE were confirmed. The measurement data of normal distribution were expressed as mean±SD, and the consistency analysis was performed using the Kappa consistency test. The clinical diagnostic efficacy indicators were calculated using the receiver operating characteristic (ROC) curve. Results:RR (95% CI) of early suspected cases was 17.06 (9.43, 30.82). The results of IFI44L gene methylation level were in good agreement with the 2012 SLICC criteria, and the sensitivity, specificity and total coincidence rate were 90.53%, 92.56% and 91.47%, respectively. The Kappa value (95% CI) was 0.829(0.796, 0.862) ( P<0.001). The diagnostic efficiency of IFI44L gene methylation level ( Kappa value 0.817) was superior to anti-nuclear antibody, anti-SM antibody and anti-dsDNA antibody ( Kappa value 0.418, 0.216 and 0.440, respectively). The Kappa values (95% CI) of methylation between MS-HRM and pyrosequencing was 0.861(0.806, 0.916), P<0.001. Conclusion:The hypomethylation of IFI44L gene methylation level detected by MS-HRM is closely related to the occurrence and development of SLE, and its diagnostic performance is better than that of three autoantibodies in SLE diagnosis, which can be used for the early diagnosis of SLE.

OBJECTIVE: Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. METHODS: A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. RESULTS: Significant associations of PM ₁, PM _2.5, PM ₁₀, SO ₂, CO, and O ₃ exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m ³ increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM ₁, 1.30 (1.27, 1.32) for PM _2.5, 1.05 (1.04, 1.06) for PM ₁₀, 5.84 (5.39, 6.32) for SO ₂, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O ₃, respectively. Long-term PM ₁, PM _2.5, PM ₁₀, SO ₂, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. CONCLUSION Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans ; Aged ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Air Pollutants/analysis* ; Aged, 80 and over ; Particulate Matter/adverse effects* ; Cardiovascular Diseases/mortality* ; Mortality ; Neoplasms/mortality* ; East Asian People

ObjectiveTo explore the possible mechanism of Bimin Formula （鼻敏方） in treating lung-spleen qi deficiency syndrome of allergic rhinitis （AR） with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose Bimin Formula group （8 rats）， and a high-dose Bimin Formula group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （P＜0.05 or P＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （P＜0.05 or P＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （P＜0.05 or P＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （P＞0.05）. Compared with the low-dose Bimin Formula group， the expression of NF-κB protein in the high-dose group decreased （P＜0.01）. ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.