Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Objective:To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods:A total of 406 patients of primary aldosteronism with confirmed subtyping, who underwent adrenalectomy and completed follow-up in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to March 2022 were retrospectively enrolled. Clinical and biochemical data were recorded. Postoperative clinical and biochemical outcomes were assessed according to Primary Aldosteronism Surgery Outcome(PASO) consensus.Results:Complete biochemical success was achieved in 391(96.31%) of 406 primary aldosteronism patients, while partial and absent biochemical success in only 4(0.99%) and 11(2.71%) primary aldosteronism patients; Complete clinical success was seen in 217(53.45%) patients, and partial clinical success in 189(46.55%) patients. Compared to the partial clinical success group, the complete clinical success group was younger, had a greater proportion of women, a smaller body mass index, a shorter duration of hypertension, a smaller daily defined dose value for antihypertensive medication, a higher estimated glomerular filtration rate(eGFR), and a lower proportion of family history of hypertension and diabetes mellitus. Multifactorial logistic regression analysis further showed that gender( OR=2.49, 95% CI 1.42-4.35, P=0.001), body mass index( OR=1.16, 95% CI 1.05-1.28, P=0.003), antihypertensive drug daily defined dose( OR=1.83, 95% CI 1.37-2.44, P<0.001), family history of hypertension( OR=2.16, 95% CI 1.22-3.83, P=0.008), history of diabetes( OR=2.47, 95% CI 1.15-5.29, P=0.021), and eGFR( OR=0.98, 95% CI 0.97-0.99, P=0.001) were independent factors influencing clinical prognosis of primary aldosteronism. Conclusion:The postoperative complete biochemical success is higher in patients with unilateral primary aldosteronism, but only about half of all patients achieve complete clinical success.

Objective:To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS).Methods:In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value.Results:The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% ( n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% ( n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95% CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95% CI 78.88%-87.56%) and specificity was 60.50% (95% CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion:PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.

ObjectiveTo compare the air disinfection effects of different human-machine coexistence disinfection methods in the high-risk areas of airborne diseases in medical and healthcare institutions, and to provide a reference for the prevention and control of airborne diseases in medical and healthcare institutions. MethodsField trials were conducted in the fever clinic, the infection disease department, and dental clinics of a tertiary hospital in Shanghai, respectively. The existing air disinfection methods (plasma air disinfection machine, circulating air ultraviolet disinfection machine or negative pressure ventilation system), upper-room 222 nm ultraviolet germicidal system, and the combination of the existing air disinfection methods and upper-room 222 nm ultraviolet germicidal system were all used in each location in the experiment group. The control group did not adopt specific air disinfection methods. Air sampling was conducted by the six-level sieve hole microbial sampler or the flat slab exposure method. The daily air sampling time was from 8:00 a.m. to 16:00 p.m., with one sample per hour, and a total of 9 samples were taken. The disinfection effects were compared by calculating the total number of airborne bacteria colonies and the sterilization rate for each disinfection method. ResultsThe total numbers of airborne bacteria colonies in the fever outpatient infusion room, the ward and nurse station of infection disease department of 222 nm group were lower than that in the control group (P=0.005, P<0.001, P<0.001). The total numbers of airborne bacteria colonies in the fever outpatient infusion room and the dental examination room of 222 nm group were lower than that in the control group or plasma air disinfection machine group (P=0.022, P=0.014). The total numbers of airborne bacteria colonies in the nucleic acid sampling room of plasma air disinfection machine group combined with 222 nm group were lower than that in plasma air disinfection machine group (P=0.019). The total numbers of airborne bacteria colonies in the CT examination room of fever clinic of the 222 nm group were lower than that in the circulating air ultraviolet disinfection machine group (P=0.002). The total numbers of airborne bacteria colonies in the CT examination room of 222 nm group combined with circulating air ultraviolet disinfection machine were lower than that of circulating air ultraviolet disinfection machine group and the control group (P=0.008, P<0.001). The air sterilization rate of upper-room 222 nm ultraviolet germicidal system ranged from 48.04% to 73.74%. The air sterilization rate of plasma air/circulating air ultraviolet disinfection machine combined with the upper-room 222 nm ultraviolet germicidal system ranged from 6.86% to 73.77%. ConclusionUpper-room 222 nm ultraviolet germicidal system could effectively reduce airborne colonies in the air and improve air hygiene quality in both clinic and ward environments with high airborne transmission risks.

OBJECTIVE To explore the improving effect of luteolin （Lut） on placental dysfunction in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on hedgehog （Hh） signaling pathway. METHODS Twenty female rats were randomly selected as a control group and fed a normal diet. The remaining female rats were fed a high-fat and high-sugar diet for 8 weeks and then caged with male rats. Pregnant rats were administered 35 mg/kg streptozotocin intraperitoneally to establish GDM models. Successfully modeled female rats were randomly allocated to model group， SAG group （Hh signaling pathway activator SAG 50 mg/kg）， Lut low-dose group （Lut 40 mg/kg）， Lut high-dose group （Lut 80 mg/kg）， and Lut high+ITR group （Lut 80 mg/kg+Hh signaling pathway antagonist itraconazole 50 mg/kg）， with 20 rats in each group. Female rats in each drug group were intubated with the corresponding drug solution once a day for 19 days. After the final administration， the serum glucose- fat metabolic parameters （levels of fasting blood glucose and fasting insulin， insulin resistance index）， placental quality， placental permeability [Evan’s blue （EB） content]， and pathological changes in placental tissue were observed. The activities of superoxide dismutase （SOD）， the contents of malondialdehyde （MDA） and reduced glutathione （GSH）， and the protein expressions of Sonic Hh （Shh）， Patched-1 （Ptch1）， Smoothened （Smo） and Gli family zinc finger-1 （Gli1） in placental tissue were detected. HBB_ RESULTS Compared with the control group， rats in the model group showed narrow capillary lumens， perivascular fibrosis in placental tissue， and a significant increase in serum glucose-fat metabolic parameters， placental quality， contents of EB and MDA， while there was a significant decrease in SOD activity， GSH content， and protein expressions of Shh， Ptch1， Smo and Gli1 （P＜0.05）. Compared with the model group， rats in the SAG group， Lut low-dose and high-dose groups had widened capillary lumens， a significant decrease in perivascular fibrosis in placental tissue， serum glucose-fat metabolic parameters， placental qualities， EB and MDA contents， while there was a significant increase in SOD activities， GSH contents， and protein expressions of Shh， Ptch1， Smo and Gli1 （P＜0.05）， with the high-dose group showing no significant difference compared to the SAG group （P＞0.05）. The Hh signaling pathway antagonist itraconazole could significantly reverse the improving effects of Lut on the above indicators （P＜0.05）. CONCLUSIONS Lut can improve glucose metabolism parameters of GDM rats， reduce placental permeability， alleviate pathological damage to placental tissue， and reduce oxidative stress. These effects may be related to the activation of the Hh signaling pathway.

Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.

Objective:Although Wu Hu Tang has the effect of treating cough variant asthma(CVA),its specific mechanism of action remains unclear.Methods:Predicted targets,autophagy genes,cough variant asthma genes and differentially expressed genes(DEGs)of CVA of Wu Hu Tang were obtained and mined from the Traditional Chinese Medicine Systematic Pharmacology Data-base and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BAT-MAN-TCM)and TCM Integrated Pharmacology Research Platform v2.0(TCMIP),PubChem,Chemspider,Swiss Target Prediction,GEO,GeneCards and other databases.The intersection tool of line Venn diagram was used to obtain the key genes.Using Cyto-scape3.8.0 software build active ingredient-key network;Wu Hu Tang intervention CVA autophagy targets with autophagy genes corre-lation analysis;Use the STRING database,Cytohubba plug-in build protein interaction network and core gene screening.GO and KEGG enrichment analysis of key targets were performed using R Biomanager and ClusterProfiler package,and finally molecular dock-ing was performed.Results:A total of 42 active ingredients,536 potential action targets,7 236 autophagy-related genes,1 987 CVA genes and 460 DEGs of Wu Hu Tang Tang were collected and screened.Thirteen key targets were obtained after taking the intersec-tion,and 12 genes were found to be statistically significant by validated used wilcoxon non-parametric test.The results of the enrich-ment analysis showed that these target genes mainly functioned in cellular autophagy through the VEGF signaling pathway,and some amino acid metabolic pathways.Conclusion:Wu Hu Tang is capable of multi-component,multi-level and multi-target involvement in autophagy-related processes to achieve intervention in CVA,which promotes the development of the idea of combining Chinese and Western medicine in the treatment of CVA and provides a new idea for the development of new clinical drugs.

Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.

Objective:To investigate pathological features and differential diagnosis in the gonads with disorder of sex development.Methods:Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People′s Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed.Results:Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT.Conclusions:Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.