Severe congenital neutropenia(SCN)is a rare disease characterized by the absolute neutrophil count(ANC)less than 0.5× 109/L in peripheral circulating blood.Due to the low neutrophil count,there is an increased risk of bacterial infection.And the most common oral manifestations are severe periodontitis and recurrent oral ulcer.This paper reports a 5-year-old girl with SCN and severe pe-riodontitis.On the basis of systemic treatment,the periodontal inflammation was controlled to a certain extent through periodontal non-sur-gical treatment and regular plaque control by using the WeChat platform for follow-up and oral hygiene.

BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.

Objective:To observe the effect of exercise-regulated miR-344g-5p on the fibrosis-related SMAD genes and transforming growth factor beta (TGF-β) in the myocardia of mice modeling diabetes.Methods:Twenty-four male C57BL/6 mice (6-8 weeks old) were randomly divided into a control group ( n=12) and a type 2 diabetes group ( n=12). Each group was further divided into two subgroups based on exercise status to form a sedentary control group, an exercise control, a sedentary type 2 diabetes group and an exercise type 2 diabetes group with six mice in each subgroup. The control groups were fed a normal diet, while the type 2 diabetes groups were on a high-fat diet for 12 weeks. Type 2 diabetes was then induced by intraperitoneal injection of streptozotocin. Two weeks later, the exercise groups began 40 minutes of daily swimming training, five days a week for eight consecutive weeks. Right after that, their cardiac function was measured using a small animal ultrasound system and the derived ejection fraction (EF) and the maximal early (E) and late (A) transmitral velocities ratio (E/A ratio) in diastole. They were then sacrificed and myocardial tissue was resected and stained with Sirius red. The expression of miR-344g-5p in the myocardium was detected using quantitative polymerase chain reactions. The expression of phosphorylated SMAD3 (p-SMAD3) and TGF-β were assessed using western blotting. The Target Scan database was exploited to analyze whether there were predicted targets of miR-344g-5p and pro-fibrotic genes such as SMAD3, TGFBR2, COL1A2 and COL12A1, and to determine any correlations in the gene regulation. Results:After 22 weeks, the EF and E/A ratio in the sedentary type 2 diabetes group were (57.5±4.1)% and (1.4±0.3), respectively, both significantly lower than in the other groups. Myocardial collagen fibers in the sedentary type 2 diabetes group were significantly more abundant than in the sedentary control and exercise type 2 diabetes groups. And miR-344g-5p expression in the myocardia of the exercise type 2 diabetes group was significantly greater than that in the sedentary type 2 diabetes group. The expression of p-SMAD3 and TGF-β in the myocardia of the sedentary type 2 diabetes group was significantly higher than in the sedentary control and exercise type 2 diabetes groups. Target Scan analysis revealed that miR-344g-5p had potential binding sites with several fibrosis-related genes such as SMAD3, TGFBR2, COL1A2, and COL12A1. Based on the reduction in TGF-β and p-SMAD protein expression in the exercise type 2 diabetes group, it was hypothesized that miR-344g-5p may inhibit the post-transcriptional processes of those genes.Conclusions:Exercise promotes the recovery of diabetic cardiomyopathy by upregulating myocardial miR-344g-5p expression, which subsequently targets and suppresses p-SMAD3 and TGF-β protein expression, thereby reducing diabetic myocardial fibrosis.

Objective:To observe the effect of exercise-regulated miR-344g-5p on the fibrosis-related SMAD genes and transforming growth factor beta (TGF-β) in the myocardia of mice modeling diabetes.Methods:Twenty-four male C57BL/6 mice (6-8 weeks old) were randomly divided into a control group ( n=12) and a type 2 diabetes group ( n=12). Each group was further divided into two subgroups based on exercise status to form a sedentary control group, an exercise control, a sedentary type 2 diabetes group and an exercise type 2 diabetes group with six mice in each subgroup. The control groups were fed a normal diet, while the type 2 diabetes groups were on a high-fat diet for 12 weeks. Type 2 diabetes was then induced by intraperitoneal injection of streptozotocin. Two weeks later, the exercise groups began 40 minutes of daily swimming training, five days a week for eight consecutive weeks. Right after that, their cardiac function was measured using a small animal ultrasound system and the derived ejection fraction (EF) and the maximal early (E) and late (A) transmitral velocities ratio (E/A ratio) in diastole. They were then sacrificed and myocardial tissue was resected and stained with Sirius red. The expression of miR-344g-5p in the myocardium was detected using quantitative polymerase chain reactions. The expression of phosphorylated SMAD3 (p-SMAD3) and TGF-β were assessed using western blotting. The Target Scan database was exploited to analyze whether there were predicted targets of miR-344g-5p and pro-fibrotic genes such as SMAD3, TGFBR2, COL1A2 and COL12A1, and to determine any correlations in the gene regulation. Results:After 22 weeks, the EF and E/A ratio in the sedentary type 2 diabetes group were (57.5±4.1)% and (1.4±0.3), respectively, both significantly lower than in the other groups. Myocardial collagen fibers in the sedentary type 2 diabetes group were significantly more abundant than in the sedentary control and exercise type 2 diabetes groups. And miR-344g-5p expression in the myocardia of the exercise type 2 diabetes group was significantly greater than that in the sedentary type 2 diabetes group. The expression of p-SMAD3 and TGF-β in the myocardia of the sedentary type 2 diabetes group was significantly higher than in the sedentary control and exercise type 2 diabetes groups. Target Scan analysis revealed that miR-344g-5p had potential binding sites with several fibrosis-related genes such as SMAD3, TGFBR2, COL1A2, and COL12A1. Based on the reduction in TGF-β and p-SMAD protein expression in the exercise type 2 diabetes group, it was hypothesized that miR-344g-5p may inhibit the post-transcriptional processes of those genes.Conclusions:Exercise promotes the recovery of diabetic cardiomyopathy by upregulating myocardial miR-344g-5p expression, which subsequently targets and suppresses p-SMAD3 and TGF-β protein expression, thereby reducing diabetic myocardial fibrosis.

OBJECTIVES: This study aimed to explore the clinical efficacy of severe early childhood caries (SECC) treatment combined with local anesthesia under general anesthesia. METHODS: A total of 108 children under 6 years old who underwent SECC dental treatment under general anesthesia at the Department of Pediatric Dentistry, Third Affiliated Hospital of Air Force Medical University from March to December 2023 were selected as the study subjects, with American Society of Anesthesiologists (ASA) classification of classⅠor Ⅱ. The study subjects were divided into a control group (n=54) and an experimental group (n=54) by retrieving intraoperative cases and postoperative follow-up records. The control group was given general anesthesia through inhalation combined with nasotracheal intubation, whereas the experimental group was given local anesthesia with 2% lidocaine on each treated tooth on the basis of general anesthesia. The basic information, preoperative anesthesia depth, hemodynamic changes during different surgical procedures, postoperative pain, and adverse reactions in the two groups were recorded and analyzed. RESULTS: No statistically significant difference was found in the basic information and preoperative anesthesia depth between the two groups (P>0.05). Among the three procedures (pulpotomy, root canal treatment, and tooth extraction), the three observed indicators in the experimental group were significantly lower than those in the control group (P<0.05). The proportion of patients in the experimental group who needed to take analgesic measures in accordance with the modified facial pain scale (FPS-R) score was significantly lower than that in the control group at postoperative wakefulness and 2 h after surgery (P<0.05). Meanwhile, no statistically significant difference was observed between the groups at 24 h after surgery (P>0.05). The proportion of patients in the experimental group who needed to take analgesic measures on the basis of the parent posto-perative pain measurement (PPPM) score was significantly lower than that in the control group when they were awake after surgery (P<0.05). No statistically significant difference was found between the groups at 2 and 24 h after surgery (P>0.05). Moreover, no statistically significant difference was observed in the incidence of adverse reactions between the two groups at 24 h after surgery (P>0.05). CONCLUSIONS The combination of local anesthesia during SECC dental treatment under general anesthesia results in minimal changes in intraoperative hemodynamics and mild postoperative pain response, hence worthy of clinical promotion.
Humans ; Anesthesia, General ; Child, Preschool ; Dental Caries/therapy* ; Pain, Postoperative/prevention & control* ; Anesthesia, Local/methods* ; Male ; Hemodynamics ; Female ; Lidocaine/administration & dosage* ; Child ; Anesthetics, Local/administration & dosage* ; Anesthesia, Dental/methods*

Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Severe congenital neutropenia(SCN)is a rare disease characterized by the absolute neutrophil count(ANC)less than 0.5× 109/L in peripheral circulating blood.Due to the low neutrophil count,there is an increased risk of bacterial infection.And the most common oral manifestations are severe periodontitis and recurrent oral ulcer.This paper reports a 5-year-old girl with SCN and severe pe-riodontitis.On the basis of systemic treatment,the periodontal inflammation was controlled to a certain extent through periodontal non-sur-gical treatment and regular plaque control by using the WeChat platform for follow-up and oral hygiene.

BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.

Complicated crown root fracture is a serious combined fracture of the enamel,dentin,and cementum in dental trauma.The treatment method is complicated.During the procedure,the condition of pulp,periodontal,and tooth body should be thoroughly evaluated,and a multidisciplinary approach combined with sequential treatment is recom-mended.This case reported the different treatment and repair processes of one case of two affected teeth after complicat-ed crown root fracture of upper anterior teeth,including regrafting of broken crown after flap surgery at the first visit,di-rect resin repair to remove broken fragments,and pulp treatment and post-crown repair at the second visit.After 18 months of follow-up,the preservation treatment of the affected teeth with complicated crown root fracture was achieved.Therefore,fragment reattachment and post-crown restoration are feasible treatment options for children with complicated crown root fracture.

BACKGROUND:Current osteoarthritis modeling methods include anterior cruciate ligament transection(ACLT)and ACLT combined with medial meniscal anterior horn resection.ACLT requires excessive postoperative exercise,which is time and labor-intensive.Complete removal of anterior horn of the medial meniscus can cause collateral damage and increase variability in modeling outcomes,requiring higher surgical skills from the surgeon. OBJECTIVE:To modify and simplify the traditional method to create animal osteoarthritis model and compare osteoarthritis symptoms of different modeling methods under a low-load exercise environment. METHODS:Forty-eight Sprague-Dawley rats were randomly assigned in four groups(n=12 per group):sham operation(complete exposure of the knee cavity of the left hind limb followed by suturing the joint cavity and skin),ACLT,ACLT+anterior horn resection(removal of the anterior horn of the medial meniscus)and ACLT+anterior horn tear(anterior horn tear of the medial meniscus).At 4 weeks after modeling,the rats were euthanized and their knee specimens were collected for gross observation,X-ray and CT scans,pathological observation,and PCR detection. RESULTS AND CONCLUSION:Gross observation:Mild meniscal wear was observed in the ACLT group.In the ACLT+anterior horn tear group,severe wear of the lateral condyle articular surface,mild wear of the medial condyle articular surface,severe meniscal wear,and full wear of the medial meniscus were observed.The ACLT+resection group showed severe wear of the lateral condyle articular surface,mild wear of the medial condyle articular surface,absence of the anterior horn of the medial meniscus,and meniscus wear area＞50%.Imaging examinations showed no significant difference among the four groups.However,the anterior tibial translocation sign was observed in the three operation groups and the anterior horn of the medial meniscus was missing in the ACLT+anterior horn resection group.Histopathological section observation:Hematoxylin-eosin,toluidine blue,and Sirius red staining showed smooth joint surfaces in the sham operation group and ACLT group;cartilage damage and matrix degradation were evident in the ACLT+anterior horn tear and ACLT+anterior horn transection groups,with less cartilage damage and matrix degradation in the ACLT+anterior horn tear group.PCR results showed higher mRNA expressions of interleukin 1β,interleukin 6,interleukin 8,tumor necrosis factor α,matrix metalloproteinase 1 and matrix metalloproteinase 3 and lower mRNA expressions of aggrecan in the ACLT+anterior horn tear group and ACLT+anterior horn resection group than in the sham operation group and ACLT group(P＜0.05).The mRNA expressions of interleukin 6,matrix metalloproteinase 1,and matrix metalloproteinase 3 were higher in the ACLT + anterior horn resection group than in the ACLT +anterior horn tear group(P＜0.05).To conclude,ACLT alone is less likely to induce osteoarthritis with obvious cartilage wear.ACLT combined with anterior horn resection or tear of the medial meniscus can induce obvious symptoms of osteoarthritis and achieve similar modeling effects.