eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

BACKGROUND:The AO12-C type middle-proximal humeral fractures are usually caused by high-energy injuries,accompanied by comminuted fractures and a large number of butterfly-shaped bone fragments.These fractures are difficult to achieve good reduction and effective fixation.With the increasing understanding of the biological characteristics of bone and soft tissue,surgical treatment is gradually shifting towards minimally invasive steel plates and intramedullary nail fixation.However,there has been no consensus on which is the best surgical technique for treating humeral fractures in minimal invasive plate osteosynthesis and intramedullary nail.OBJECTIVE:To compare the clinical effect of minimal invasive plate osteosynthesis and intramedullary nail for treating AO12-C type middle-proximal humeral fractures.METHODS:A retrospective analysis was performed in 36 patients with AO12-C type middle-proximal humeral fracture who met the inclusion criteria admitted to the Guizhou Hospital of Beijing Jishuitan Hospital from January 2020 to December 2022.All patients were assigned to minimal invasive plate osteosynthesis group(18 cases)and intramedullary nail group(18 cases)according to the surgical treatment plan.The minimal invasive plate osteosynthesis group received minimally invasive plate osteosynthesis based on preoperative planning assisted by 3D printing,while the intramedullary nail group received intramedullary nail internal fixation.Operation time,intraoperative blood loss,hospital stay,and fracture healing time were compared between the two groups.Visual analog scale score at 1,3,and 6 months after surgery,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score,and complications of the shoulder joint at the last follow-up were compared between the two groups.RESULTS AND CONCLUSION:(1)All patients were followed-up for average(15.56±4.05)months,and no difference was observed in hospital stay and fracture healing time between the two groups(P＞0.05).The minimal invasive plate osteosynthesis group had shorter operation time compared to the intramedullary nail group(P＜0.05).The intramedullary nail group had less intraoperative blood loss between the two groups of patients(P＜0.05).(2)In the intramedullary nail group,at 1 and 3 months after operation,the visual analog scale score was significantly lower than the minimal invasive plate osteosynthesis group(P＜0.05).No difference was observed in the visual analog scale in long-term follow-up,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score at the last follow-up between the two groups(P＞0.05).(3)No complications such as nonunion or wound infection occurred in either group.Two cases of radial nerve palsy occurred in minimal invasive plate osteosynthesis group,both of which recovered within 3 months.The intramedullary nail group had 1 case of rotator cuff injury.There was no significant difference in the rate of complications between the two groups(P＞0.05).(4)To conclude,minimal invasive plate osteosynthesis and intramedullary nail can achieve good clinical efficacy in the treatment of AO12-C type middle-proximal humeral fractures,effectively improving shoulder joint function in patients.However,minimal invasive plate osteosynthesis exhibits obvious advantages in shorter surgical time with the assistance of 3D printing,which is a valuable,effective,and safe method for treating AO12-C type middle-proximal humeral fractures.

Objective To analyze the research progress of acupuncture and moxibustion in the treatment of simple obesity,thus to provide reference for further research in this field.Methods The relevant literature in China National Knowledge Infrastructure(CNKI)and Wanfang Data Knowledge Service Platform in the past 24 years were retrieved,and analysis of authors,institutions,and keywords were carried out by CiteSpace 6.2.R6 software,and visualization maps were drawn.Results A total of 889 valid articles were included,and the number of annual publications tended to be stable;the authors in this field were Zhou Zhongyu and Chen Xia as the core author team;the most involved research institution in the institutional cooperation map was the Nanjing University of Chinese Medicine;the high-frequency keywords mainly concentrated on"acupuncture therapy","acupuncture and muxibustion therapy","simple obesity","acupoint catgut embedding therapy",etc.;the keyword clusters covered a total of 13 items,namely"electroacupuncture","acupuncture","acupuncture and moxibustion","acupoint catgut embedding",etc.Conclusion There are many studies on acupuncture and moxibustion in the treatment of simple obesity,and the hot spots of the study are focused on small-sample clinical observation,literature research,and research on the mechanism of action.In the future,researchers can conduct further high-quality studies as well as research on the application and mechanism of action of specific acupuncture therapies,with the aim of developing the preferable therapeutic approaches of acupuncture for the treatment of simple obesity.

Based on the theory of"body fluid and blood sharing the same origin",this paper reveals that the core pathogenesis of atopic dermatitis(AD)lies in the abnormal distribution and transformation of body fluid and blood,which is closely related to dysfunction of the lung,spleen,and kidney.Integrating modern medical research on immune regulation and skin barrier function,we propose that in the early stage of AD,due to deficient endowment,acquired loss of nutrition,insufficiency of the spleen and kidney,and failure of the lung-defense system to protect,external pathogens stagnate in the fleshy exterior.This leads to dysfunction of the lung's governance over the skin,impaired distribution of body fluid,obstruction of qi and blood circulation,and stagnation in the skin,resulting in exudative dampness.The dampness stagnates and transforms into heat.Acupuncture should primarily focus on clearing the lung,dispersing stagnation,distributing body fluid,and unblocking collaterals.In the middle and late stages,as lung disease affects the spleen and kidney,acupuncture should emphasize supplementing and tonifying the spleen and kidney,nourishing blood,and moistening dryness,while simultaneously addressing both the root and the branch.For intractable pruritus,fire needling or pricking-collateral cupping can be employed to control itching and reduce recurrence.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

BACKGROUND:The AO12-C type middle-proximal humeral fractures are usually caused by high-energy injuries,accompanied by comminuted fractures and a large number of butterfly-shaped bone fragments.These fractures are difficult to achieve good reduction and effective fixation.With the increasing understanding of the biological characteristics of bone and soft tissue,surgical treatment is gradually shifting towards minimally invasive steel plates and intramedullary nail fixation.However,there has been no consensus on which is the best surgical technique for treating humeral fractures in minimal invasive plate osteosynthesis and intramedullary nail.OBJECTIVE:To compare the clinical effect of minimal invasive plate osteosynthesis and intramedullary nail for treating AO12-C type middle-proximal humeral fractures.METHODS:A retrospective analysis was performed in 36 patients with AO12-C type middle-proximal humeral fracture who met the inclusion criteria admitted to the Guizhou Hospital of Beijing Jishuitan Hospital from January 2020 to December 2022.All patients were assigned to minimal invasive plate osteosynthesis group(18 cases)and intramedullary nail group(18 cases)according to the surgical treatment plan.The minimal invasive plate osteosynthesis group received minimally invasive plate osteosynthesis based on preoperative planning assisted by 3D printing,while the intramedullary nail group received intramedullary nail internal fixation.Operation time,intraoperative blood loss,hospital stay,and fracture healing time were compared between the two groups.Visual analog scale score at 1,3,and 6 months after surgery,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score,and complications of the shoulder joint at the last follow-up were compared between the two groups.RESULTS AND CONCLUSION:(1)All patients were followed-up for average(15.56±4.05)months,and no difference was observed in hospital stay and fracture healing time between the two groups(P＞0.05).The minimal invasive plate osteosynthesis group had shorter operation time compared to the intramedullary nail group(P＜0.05).The intramedullary nail group had less intraoperative blood loss between the two groups of patients(P＜0.05).(2)In the intramedullary nail group,at 1 and 3 months after operation,the visual analog scale score was significantly lower than the minimal invasive plate osteosynthesis group(P＜0.05).No difference was observed in the visual analog scale in long-term follow-up,shoulder joint function,Constant-Murley score,Quick Disabilities of the Arm,Shoulder and Hand(QuickDASH)score at the last follow-up between the two groups(P＞0.05).(3)No complications such as nonunion or wound infection occurred in either group.Two cases of radial nerve palsy occurred in minimal invasive plate osteosynthesis group,both of which recovered within 3 months.The intramedullary nail group had 1 case of rotator cuff injury.There was no significant difference in the rate of complications between the two groups(P＞0.05).(4)To conclude,minimal invasive plate osteosynthesis and intramedullary nail can achieve good clinical efficacy in the treatment of AO12-C type middle-proximal humeral fractures,effectively improving shoulder joint function in patients.However,minimal invasive plate osteosynthesis exhibits obvious advantages in shorter surgical time with the assistance of 3D printing,which is a valuable,effective,and safe method for treating AO12-C type middle-proximal humeral fractures.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.

Nasopharyngeal carcinoma is a common malignant tumor in southern China, and its occurrence and development mechanism are still not fully understood. However, a large number of studies have shown that DNA methylation has important clinical application value in the screening, diagnosis, treatment and prognosis evaluation of nasopharyngeal carcinoma. DNA methylation affects the division cycle, growth, invasion and migration of nasopharyngeal carcinoma cells by regulating the transcription and protein expression levels of genes associated with tumorigenesis and development. In addition, there are significant differences in DNA methylation expression levels in different stages of nasopharyngeal carcinoma, which provides theoretical guidance and clinical reference for the early diagnosis, timely treatment and response evaluation of nasopharyngeal carcinoma. Current studies have shown that DNA methylation detection may provide a simple and efficient early screening method for nasopharyngeal carcinoma, and can also explore new ideas for the development of non-invasive screening methods.