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 investigate the correlation between the expression of integrin α 2(ITGA2)and recurrence risk of papillary thyroid microcarcinoma(PTMC).Methods PTMC and para-carcinoma tissue were collected from patients who underwent surgery and pathologically confirmed at the hospital from Decem-ber 2022 to June 2023,and the expression of ITGA2 in PTMC and paracarcinoma tissue were observed using immunohistochemistry method.Clinical characteristics of all patients were collected and the differences in clin-icopathological characteristics between patients in ITGA2-positive and-negative groups were compared.Ac-cording to the risk stratification criteria for tumor recurrence,the differences in ITGA2 expression between groups were compared.Results The expression level of ITGA2 in PTMC was higher than that in para-carci-noma tissues,and the difference was statistically significant(P＜0.001).Multivariate logistic regression anal-ysis showed that BRAF mutation(OR=2.668)and larger total tumor diameter(TTD,OR=1.111)were risk factors for ITGA2 overexpression(P＜0.05).ITGA2 positive expression was associated with the risk of tumor recurrence(P=0.009).Conclusion ITGA2 can be used as a novel molecular biomarker for clinical ap-plication.

Objective:To investigate the risk factors for severe distal curve progression after posterior hemivertebra (HV) resection and short-segment fixation in patients with congenital cervicothoracic scoliosis (CTS), and to analyze the surgical revision strategy.Methods:Imaging and clinical data of patients who underwent posterior HV resection and short-segment fixation for CTS between August 2012 and August 2021 at Nanjing Drum Tower Hospital were retrospectively analyzed. A total of 55 patients were recruited, including 27 females and 28 males with an average age of 8.5±3.6 years (range 3-15 years) at surgery and an average Risser grade of 0.7±1.4 (range 0-4). The number of fused segments averaged 6.9±1.6 (range 4-10), and the mean follow-up was 38.7±18.9 months (range 9-94 months). According to the severity of distal curve progression, the recruited patients were divided into three groups: non-progression group (NPG), mild progression group (MPG), and severe progression group (SPG). The latter two groups were collectively called the progression group (PG). The cervicothoracic Cobb angle, T1 tilt angle, coronal balance distance (CBD), neck tilt angle, clavicular angle, head tilt angle, head shift, and upper (UIV) and lower instrument vertebra (LIV) tilt angle on the standing whole spine X-ray were measured before and after surgery and at the last follow-up. The correction rate of the Cobb angle in the osteotomy area was measured and calculated on CT three-dimensional reconstruction, and the proportion of patients with Klippel-Feil syndrome (KFS) was recorded. Statistical analysis was conducted on the various parameters between the two groups. For factors with statistical significance in the single-factor analysis, binary logistic regression analysis was performed to identify the high-risk factors for distal curve progression.Results:There were 38 cases in the NPG, 11 in the MPG, and 6 in the SPG. Compared to the NPG, the PG showed more severe coronal imbalance preoperatively, with CBD of 35.6±22.3 mm and 11.6±7.1 mm respectively; more severe neck tilt and head shift, with neck tilt angle of 17.4°±8.3° and 12.4°±6.9° respectively, and head shift of 22.8±17.7 mm and 13.9±9.8 mm respectively; and a higher proportion of KFS, 65% (11/17) and 34% (13/38) respectively, all with statistical significance ( P<0.05). Postoperatively, the PG showed more severe coronal imbalance compared with the NPG, with 17.3±12.7 mm and 9.6±8.1 mm respectively; more evident residual deformity, with cervical tilt angles of 9.4°±4.6° and 6.4°±5.3° respectively, and head shift of 14.7±7.4 mm and 9.1±5.9 mm respectively; lower correction of Cobb angle in the apical osteotomy region, with rates of 40.1%±15.2% and 50.3%±19.9% respectively; more significant UIV and LIV tilt, with UIV tilt angles of 14.3°±7.4° and 9.8°±5.3° respectively, and LIV tilt angles of 8.1°±5.5° and 4.5°±3.6° respectively, all with statistical significance ( P<0.05). SPG showed only more severe coronal imbalance preoperatively compared with the MPG, with 50.7±31.3 mm and 27.3±9.6 mm respectively; and head shift, with 33.5±25.0 mm and 16.9±11.0 mm respectively, all with statistical significance ( P<0.05). Logistic regression analysis demonstrated a significant correlation between significant preoperative coronal imbalance and postoperative distal scoliosis progression [ OR=1.299, 95% CI (1.101, 1.531), P=0.002]. Five cases (83.3%) in SPG underwent revision surgery with an average follow-up of 25 months, and selecting the LIV down to the stable region was the major revision strategy. Conclusion:Combined KFS, residual cervicothoracic deformities, and tilting of UIV and LIV are key causes, whereas significant preoperative coronal imbalance is an independent risk factor predisposing to the distal curve progression.

Objective:To compare the clinical outcomes between three-column osteotomy and posterior-column osteotomy for correcting dystrophic kyphoscoliosis secondary to neurofibromatosis type 1 (DKS-NF1).Methods:ALL of 84 patients with DKS-NF1 were retrospectively analyzed, and the average age was 17.7±6.9 years. There were 50 cases with single curve, 18 cases with double curves, and 16 cases with triple curves; kyphosis was found in 42 cases in the thoracic area, 31 cases in the thoracolumbar area, and 11 cases in the lumbar area. The patients were divided into two groups: posterior column osteotomy group and three column osteotomy group based on surgical strategy. The radiographic parameters (including the magnitude of kyphosis, scoliosis, coronal balance distance, etc.) were compared between the two groups before and after surgery, and during the follow-up. The surgical efficacy was also compared based on the spinal correction and complications (such as cerebrospinal fluid leakage, pneumothorax, rod breakage, etc.).Results:The posterior column osteotomy group consisted of 74 patients and the column osteotomy group consisted of 10 patients. The age of patients in the posterior column osteotomy group was significantly younger than that in the three-column osteotomy group (15.8±4.8 years vs. 29.4±10.2 years, t=7.088, P<0.001), and the proportion of preoperative traction in this group was significantly higher than that in the three column osteotomy group (26/74 vs. 0, P=0.027). The apex of kyphosis in the three-column osteotomy group mainly located in the thoracolumbar and lumbar area, significantly higher than that in the posterior column osteotomy group (10/10 vs. 32/74, P=0.001). The magnitude of kyphosis in the two groups were 73.8°±20.9° and 63.1°±21.4° before surgery, respectively ( t=1.506, P=0.136). After surgery, they were corrected to 43.1°±20.9° and 21.1°±22.8°, respectively ( t=3.066, P=0.003), with correction rates of 43.7% ±19.6% and 84.1% ±78.7%, respectively ( t=3.677, P<0.001). At the last follow-up, they were maintained at 46.5°±20.9° and 24.6°±25.5°, respectively ( t=3.016, P=0.003). The Cobb angle of the main curve was corrected from preoperative 83.0°±29.0° and 66.3°±17.7° ( t=1.766, P=0.081) to postoperative 50.6°±20.8° and 40.8°±15.6° ( t=1.436, P=0.155), with correction rates of 38.3% ±16.6% and 39.3% ±12.7% ( t=0.191, P=0.849), respectively. At the last follow-up, they were maintained at 52.3°±20.5° and 43.1°±18.2°, respectively ( t=1.339, P=0.185). The proportion of multi-rod system application and screw density in three column osteotomy group was significantly higher than that in posterior column osteotomy group (8/10 vs. 20/74, P=0.002; 72.0% ±11.3% vs. 61.4% ±14.6%, t=2.173, P=0.033). The incidence of complications in the two groups was 12.2% (posterior column osteotomy group, 9/74) and 20% (three column osteotomy group, 2/10), respectively, with no statistically significant difference ( P=0.613). Conclusion:Three-column osteotomy is mainly used to treat adult kyphosis in DKS-NF1 patients. While the posterior column osteotomy methods were mainly applied in young patients. Most patients can achieve the purpose of deformity correction by posterior column osteotomy alone or combined with anterior complementary fusion. For patients with severe kyphosis, preoperative Halo gravity traction can help to further correct the intraoperative deformities.

Objective To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation.Methods A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024.Additionally,a literature review was conducted.Results All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels,and one child was initially identified through neonatal genetic metabolic disease screening.According to the literature review,there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation(including the four children in this study).Among these,12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome,while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine(C5-OH)during neonatal genetic metabolic disease screening.Conclusions Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome,detectable as early as during neonatal genetic metabolic disease screening.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Porcine parvovirus(PPV)is a causative agent of porcine parvovirus infection(PPI),which significantly impacts the pig industry due to its association with reproductive dysfunction.The condition is characterized by stillbirth,mummified fetuses,fetal weakness,and abortion in pregnant sows.The pathogenic mechanism remains incompletely understood,with no effective therapeutic drugs available currently.Despite extensive research on the host's response to PPV in-fection and identification of various signaling pathway transduction mechanisms,a comprehensive understanding is still lacking.This review aims to summarize the current knowledge regarding al-terations in related signaling pathways following PPV infection,provide novel insights into the pathogenesis of PPV and facilitate the drug development.

This study aims to investigate the effects of Japanese encephalitis virus(JEV)on TLRs signaling pathway and its regulation of the secretion of inflammatory factors during the infection of testicular interstitial cells,In this study,the mRNA levels of TLR3,TLR7,TLR8,TRIF and MyD88 genes were detected by qPCR after 1 MOI dose of JEV was inoculated into testicular stro-mal cells at different time periods.Western blot assay was used to detect the expression levels of TLR3,TLR7,TRIF and MyD88 protein at 6 h after JEV infection,and ELISA was used to detect the expression levels of IL-1β,IL-6 and TNF-α at different time periods(6,12 and 24 h).The re-sults showed as follows:After 6 h of JEV infection,the mRNA levels of TLR3,TLR7,TRIF and MyD88 genes were significantly up-regulated(P＜0.05),and the mRNA levels of TLR8 genes were down-regulated(P＜0.05).Western blot results showed that the protein expressions of TLR3,TLR7,TRIF and MyD88 were significantly up-regulated when JEV infected testicular stromal cells for 6 h(P＜0.05),which was consistent with the corresponding mRNA transcription levels.There was no significant change in TLR8 protein expression.ELISA results showed that 6 h after JEV infection of testicular stromal cells,IL-6 was significantly increased(P＜0.01),and the expressions of IL-1β and TNF-α were not changed.TLR3,TLR7,TLR8,TRIF and MyD88 were si-lenced by siRNA,and the silenced cells were inoculated with JEV for 6 h,and IL-6 expression lev-els were detected by ELISA.The results showed that silenced TLR3,TLR7,TLR8,TRIF and MyD88 could significantly reduce the increase of IL-6 secretion induced by JEV infection(P＜0.05).These results indicated that JEV could induce the expression of inflammatory factor IL-6 by activating TLR3,TLR7 and TLR8 signaling pathway after infection of testicular stromal cells.This study provides a reference for further elucidating the mechanism of reproductive disorders caused by JEV infection.

Porcine circovirus type 2(PCV2)is the main pathogen causing porcine circovirus related diseases.PCV2 infection in pigs may lead to porcine dermatitis and nephrotic syndrome(PDNS)and weaned piglets multiple system failure syndrome(PMWS),etc.At present,the pathogenic mechanism is not fully understood.PCV2 is a single strand of negative link DNA,which can cause immune suppression in the body and lead to increased secondary susceptibility,which has a syner-gistic effect with various pig diseases and brings major economic losses to the pig industry.Al-though there are commercial vaccines,the prevention of vaccines has certain limitations and there is no effective drug treatment so far,an outbreak will threaten people's life and health and public safety,resulting in significant economic losses.In order to understand the latest progress of PCV2 escape mechanism and prevention and control,this paper summarizes the inhibition of interferon production,regulation of apoptosis,regulation of autophagy,regulation of pyroptosis and inflam-matory response,evasion of adaptive immune response,and prevention and control of PCV2,in or-der to provide new theoretical ideas for the research and prevention and control of PCV2.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.