The morphological changes and functions of mitochondria are closely associated with the development and progression of non-alcoholic fatty liver disease （NAFLD）. Dynamin-related protein 1 （Drp1） is one of the primary proteins determining mitochondrial fission， and its activity is strictly controlled to ensure the balance of mitochondrial dynamics according to cellular needs. Drp1 can enhance mitochondrial interactions and mitochondrial fission by promoting the formation of endoplasmic reticulum tubules， and the phosphorylation state and deacetylation of Drp1 can also affect the morphological changes of mitochondria， thereby affecting the status of NAFLD. This article elaborates on the role and mechanism of action of Drp1 in the progression of NAFLD， in order to provide ideas for targeted therapy for NAFLD.

OBJECTIVE To evaluate the comprehensive value of novel oral anticoagulant drugs （NOACs） after major orthopedic surgery. METHODS The evaluation evidence was collected through literature research； evidence and value：impact on decision-making （EVIDEM） framework was introduced to integrate the evaluation process； the multi-criteria decision analysis （MCDA） method was used to construct a multi-dimensional evaluation system； the weights assigned to each evaluation criterion were determined by the combination of Delphi method and analytic hierarchy process， and the rivaroxaban， dabigatran and apixaban were comprehensively evaluated. RESULTS The clinical comprehensive evaluation system of NOACs after major orthopedic surgery was successfully established， and the final clinical comprehensive evaluation weights of NOACs （rivaroxaban， dabigatran， apixaban） after major orthopedic surgery were calculated， with scores of 0.399 7 for rivaroxaban， 0.244 4 for apixaban， and 0.355 9 for dabigatran， indicating that rivaroxaban demonstrated the highest overall clinical value. Among them， rivaroxaban had the highest weight score in the evaluation of pharmaceutical characteristics， cost-effectiveness and other attributes in a single dimension. In terms of efficacy and safety evaluation， apixaban had the highest weighting score. CONCLUSIONS Among NOACs， rivaroxaban is more suitable for routine anticoagulation management after major orthopedic surgery， especially in terms of pharmacological properties， cost-effectiveness and other attributes.

[摘 要] 目的：探讨组蛋白去乙酰化酶（HDAC）抑制剂西达苯胺联合CHOP方案治疗初诊外周T细胞淋巴瘤（PTCL）的临床疗效，并分析其预后影响因素。方法：收集2012年4月至2022年8月期间在南通大学附属医院初诊为PTCL且未接受过放化疗的患者的临床资料。根据患者接受的一线治疗方案，分为西达苯胺 + CHOP组（n = 20）和CHOP组（n = 24）。通过卡方检验或Fisher确切检验比较两组间临床病理特征的差异，使用Kaplan-Meier法生成生存曲线，采用Log-Rank检验进行单因素生存分析。进行亚组分析，评估西达苯胺 + CHOP组患者的生存结局，并通过相互作用测试，以评估影响两组生存预后差异的相关因素。结果：两组患者基线（年龄、性别、肿瘤分期）基本均衡，但西达苯胺 + CHOP组血管免疫母细胞性T细胞淋巴瘤（AITL）患者较多（70.8% vs 15%），PTCL-非特指型（NOS）患者较少（16.7% vs 30%）。疗效分析显示，西达苯胺 + CHOP治疗的患者中位无进展生存期（PFS）显著延长（7个月 vs 3个月，P = 0.032），中位OS也显著延长（20个月 vs 6个月，P = 0.004）。单因素预后分析发现，与无B症状PTCL患者相比，有B症状患者的PFS（P = 0.053）和OS（P = 0.065）均较差；且基线乳酸脱氢酶（LDH）较高的患者OS较差（P = 0.056）。进一步亚组疗效分析显示，在基线血清铁蛋白水平正常的患者中，西达苯胺 + CHOP组患者的PFS显著优于CHOP组[95% CI（1.14, 43.58）]；血清铁蛋白水平和治疗方案之间的相互作用检验具有统计学意义（P = 0.042）。结论：西达苯胺联合CHOP方案对初诊PTCL患者有生存获益，且基线血清铁蛋白水平可作为联合治疗的潜在预测标志物。

OBJECTIVE: To compare early graft healing between over-the-top (OTT) and anatomic single-bundle (SB) anterior cruciate ligament (ACL) reconstruction. METHODS: A clinical data of 40 patients underwent ACL reconstruction, who admitted between June 2021 and October 2022 and met the selective criteria, was retrospectively analyzed. Among them, 20 patients were treated with OTT reconstruction (OTT group) and 20 with SB reconstruction (SB group). There was no significant difference between groups ( P>0.05) in the gender, age, affected side, disease duration, degree of meniscus injury, body mass index, and preoperative International Knee Documentation Committee (IKDC) score, Lysholm score, pain visual analogue scale (VAS) score, and KT-2000 measurement. At 3, 6, and 12 months, MRI was performed to measure the signal noise quotient (SNQ) of the proximal end, middle, and distal end of the graft in the two groups, as well as at the corner of the graft with lateral femoral condyle and 1 cm around the femoral fixation point in the OTT group, to observe the degree of graft healing. Before operation and at 3, 6, and 12 months, the knee function and pain were evaluated by IKDC score, Lysholm score, and VAS score. Before operation and at 12 months after operation, the KT-2000 measurement was taken to evaluation the knee joint stability. RESULTS: All operations were successfully completed in both groups and the incisions healed by first intention. All patients were followed up 12-15 months (mean, 12.9 months), with no significant difference in the follow-up time between groups ( P>0.05). After operation, the IKDC score, VAS score, and Lysholm score improved gradually over time in both groups, with significant differences between different time points ( P<0.05). The differences between groups at 3, 6, and 12 months after operation were not significant ( P>0.05). The anterior and posterior stability of the knee joint improved significantly in both groups at 12 months after operation, and the difference in KT-2000 measurements was significant when compared with the preoperative value ( P<0.05), but the difference of pre- and post-operation between groups was not significant ( P>0.05). At 3, 6, and 12 months after operation, MRI showed that the differences in the SNQ of the proximal end and middle of the grafts between the two groups were not significant ( P>0.05), and the SNQ of distal end was significantly higher in the SB group than in the OTT group ( P<0.05). At each time point, grafts in the OTT group had the highest SNQ at the corner and the lowest at the fixation point, and the differences were significant compared to the other sites ( P<0.05). In the two groups, except for the fixation point, the SNQ of the remaining sites were highest at 6 months and lowest at 12 months ( P<0.05). In addition, there were significant differences in SNQ between the different sites of grafts ( P<0.05), and the SNQ was lowest at proximal end and highest at distal end. At last follow-up, the knee grafts in both groups were in good shape and no graft necrosis or loosening of the internal fixation was observed. CONCLUSION The knee joint function and graft healing after OTT reconstruction of ACL are similar to those of SB reconstruction, but it should be noted that the healing at the corner of the graft is slower.
Retrospective Studies ; Treatment Outcome ; Anterior Cruciate Ligament Reconstruction/rehabilitation* ; Follow-Up Studies ; Tibial Meniscus Injuries/surgery* ; Patient Positioning/methods* ; Recovery of Function ; Pain Measurement ; Knee Joint/surgery* ; Humans ; Male ; Female ; Adult ; Wound Healing

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway is a crucial component of the immune system. It detects abnormal cytosolic double-stranded DNA and promotes the expression of type I interferons and other inflammatory factors, thereby protecting the body from pathogenic infections. In children, an immature immune system or genetic mutations can lead to immune dysregulation, increasing the risk of autoimmune diseases (AID) and autoinflammatory diseases. Recent studies have shown that aberrant activation of the cGAS-STING signaling pathway is associated with the development of AID and autoinflammatory diseases in children. This review summarizes the research progress on the cGAS-STING signaling pathway in childhood AID and autoinflammatory diseases, aiming to provide new directions for clinical diagnosis and treatment.
Humans ; Nucleotidyltransferases/physiology* ; Membrane Proteins/physiology* ; Signal Transduction/physiology* ; Child ; Autoimmune Diseases/immunology* ; Inflammation/etiology*

BACKGROUND: Despite some studies identifying a potential association between obesity and chronic obstructive pulmonary disease (COPD) risk, previous research had overlooked the dynamic nature of body weight over time, leading to inconsistent findings. The purpose of this study is to elucidate the relationship between adult weight change and COPD risk by adjusting for potential confounding factors. METHODS: We conducted a retrospective analysis using data from ten NHANES cycles (1999-2018), including adults aged 40-74 years. Weight change patterns were assessed using BMI at three time points and classified into five categories per period. Absolute weight change was also grouped into five levels. Multivariate logistic regression models, incorporating sampling weights, were used to examine associations between weight change and COPD, adjusting for demographic and lifestyle covariates. RESULTS: Compared with participants who maintained normal weight, stable obesity participants had increased risk of COPD from age 25 years to 10 years before the survey (OR = 1.45, 95% CI = 1.15 to 1.83), in the 10 years period before the survey (OR = 1.75, 95% CI = 1.47 to 2.08), and from age 25 years to survey (OR = 1.84, 95% CI = 1.46 to 2.31). Three periods indicate that weight gain in adulthood was associated with risk of COPD. In addition, substantial weight gain of more than 20 kg was associated with a higher risk of COPD. In stratified analyses, we also observed a more significant association between weight change and the risk of COPD in never smokers compared to former smokers. CONCLUSIONS Our study suggested that stable obesity and weight gain in adulthood were associated with an increased risk of COPD compared to those who maintain a normal weight, and that the association between weight gain and the incidence of COPD appears closer in patients who have never smoked.
Humans ; Pulmonary Disease, Chronic Obstructive/etiology* ; Middle Aged ; Male ; Female ; Adult ; Aged ; Retrospective Studies ; Weight Gain ; Obesity/complications* ; Risk Factors ; United States/epidemiology* ; Nutrition Surveys ; Body Mass Index

OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

OBJECTIVE: To evaluate the clinical diagnostic value of knee MRI at 90° flexed position for Ramp lesions of medial meniscus. METHODS: A total of 228 patients with knee pain as the main complaint who were admitted between September 2021 and September 2023 was selected as the research subjects, of which 51 patients met the selection criteria and were enrolled in the study. There were 31 males and 20 females with an average age of 38.6 years (range, 15-67 years). Body mass index was 17.2-28.7 kg/m ² (mean, 23.9 kg/m ²). There were 25 cases of left knee and 36 cases of right knee. The time from injury to admission was 0.1-14.3 weeks (mean, 2.1 weeks). Preoperative knee MRI at fully extended position (knee extension position) and 90° flexed position (knee flexion position) were performed to determine the presence of irregular signs at the posterior edge of the medial meniscus, and PHMM fluid high signal [i.e. complete fluid filling between the posterior horn of the medial meniscus (PHMM) and the capsule margin]. Findings obtained under arthroscopy served as the "gold standard" to analyze the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of MRI at knee extension and flexion positions for the two specific signs of Ramp lesion. RESULTS: Twenty-one patients (41.2%) were diagnosed with Ramp lesions by using arthroscopy, including 1 case of Thaunat type Ⅰ, 2 cases of type Ⅱ, 6 cases of type Ⅲ, 7 cases of type Ⅳ, and 5 cases of type Ⅴ. The positive rates of irregular signs at the posterior edge of the medial meniscus on MRI at knee extension and flexion positions were significantly different from the diagnosis of Ramp injury under arthroscopy ( P<0.05). The sensitivity, specificity, accuracy, PPV, and NPV of MRI in the diagnosis of irregular signs were 76.1%, 60.0%, 66.7%, 57.1%, and 78.3% respectively at knee extension position, and 85.7%, 73.3%, 78.4%, 69.2%, and 88.0% respectively at knee flexion position. The positive rates of PHMM fluid high signal on MRI at knee extension and flexion positions were significantly different from the diagnosis of Ramp injury under arthroscopy ( P<0.05). The sensitivity, specificity, accuracy, PPV, and NPV of MRI in diagnosing PHMM fluid high signal were 38.1%, 100%, 74.5%, 100%, and 69.8% respectively at knee extension position, and 85.7%, 100%, 94.1%, 100%, and 90.9% respectively at knee flexion position. CONCLUSION Knee MRI at 90° flexed position improves the diagnostic performance of the detection of medial meniscal Ramp lesions compared with MRI at fully extended position.
Humans ; Magnetic Resonance Imaging/methods* ; Female ; Male ; Tibial Meniscus Injuries/diagnostic imaging* ; Adult ; Menisci, Tibial/diagnostic imaging* ; Middle Aged ; Adolescent ; Young Adult ; Arthroscopy/methods* ; Aged ; Knee Injuries/diagnostic imaging* ; Range of Motion, Articular ; Knee Joint/diagnostic imaging* ; Sensitivity and Specificity

Fatty acids (FA) are widely used as feed stocks for the production of cosmetics, personal hygiene products, lubricants and biofuels. Ogataea polymorpha is considered as an ideal chassis for bio-manufacturing, due to its outstanding characteristics such as methylotroph, thermal-tolerance and wide substrate spectrum. In this study, we harnessed O. polymorpha for overproduction of fatty acids by engineering its fatty acid metabolism and optimizing the fermentation process. The engineered strain produced 1.86 g/L FAs under the optimized shake-flask conditions (37℃, pH 6.4, a C/N ratio of 120 and an OD₆₀₀ of seed culture of 6-8). The fed-batch fermentation process was further optimized by using a dissolved oxygen (DO) control strategy. The C/N ratio of initial medium was 17.5, and the glucose medium with a C/N ratio of 120 was fed when the DO was higher than 30%. This operation resulted in a titer of 18.0 g/L FA, indicating the potential of using O. polymorpha as an efficient cell factory for the production of FA.
Culture Media ; Fatty Acids ; Fermentation ; Metabolic Engineering ; Saccharomycetales/metabolism*

Anterior Cruciate Ligament Reconstruction ; Femur/surgery*