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.

Objective:There are a variety of minimally invasive interventional treatments for trigeminal neuralgia,and the efficacy evaluation is different.The preferred treatment scheme is still controversial.This study aims to investigate the differences in treatment effects between patients with primary trigeminal neuralgia(PTN)treated with percutaneous balloon compression(PBC)for the first intervention and patients with pain recurrence after radiofrequency thermocoagulation(RT)who then received PBC for PTN,and to offer clinicians and patients more scientifically grounded and precise treatment alternatives. Methods:We retrospectively analyzed 103 patients with PTN admitted to the Department of Pain Management of the Second Affiliated Hospital of Guangxi Medical University from January 2020 to December 2021,including 49 patients who received PBC for the first time(PBC group)and 54 patients who received PBC for pain recurrence after RT(RT+PBC group).General information,preoperative pain score,intraoperative oval foramen morphology,oval foramen area,balloon volume,duration of compression,and postoperative pain scores and pain recurrence at each time point on day 1(T1),day 7(T2),day 14(T3),1 month(T4),3 months(T5),and 1 year(T6)were collected and recorded for both groups.The differences in treatment effect,complications and recurrence between the 2 groups were compared,and the related influencing factors were analyzed. Results:The differences of general information,preoperative pain scores,foramen ovale morphology,foramen ovale area,T1 to T3 pain scores between the 2 groups were not statistically different(all P>0.05).The balloon filling volume in the PBC group was smaller than that in the RT+PBC group,the pain scores at T4 to T6 and pain recurrence were better than those in the RT+PBC group(all P<0.05).Pain recurrence was positively correlated with pain scores of T2 to T6(r=0.306,0.482,0.831,0.876,0.887,respectively;all P<0.01). Conclusion:The choice of PBC for the first intervention in PTN patients is superior to the choice of PBC after pain recurrence after RT treatment in terms of treatment outcome and pain recurrence.

BACKGROUND:Kinesio taping is often used for the treatment of various sports injuries.The methods of foot and ankle sports taping are complex and diverse.Among them,Fascia taping is applicable to a wider range of people and can be used for different foot posture types,but it still lacks of practical verification,and its specific biomechanical role is not clear. OBJECTIVE:To observe the changes in plantar pressure characteristics of subjects with different foot positions during walking and jogging after Fascia taping. METHODS:Thirty-seven young healthy subjects were recruited from the Yantai campus of Binzhou Medical University to conduct the test.They were scored according to the foot posture index-six items version,and were divided into the supination foot group,the neutral foot group,and the pronation foot group.The static foot morphological indexes(including navicular drop,arch height index,arch height flexibility-longitudinal arch,and arch height flexibility-transverse arch)and the pressure-time integral of each foot zone during walking and jogging were collected and calculated respectively before and after Kinesio taping.The specific biomechanical mechanism of Fascia taping was analyzed. RESULTS AND CONCLUSION:(1)General data:There was no statistical difference among the three groups of subjects in general data,such as gender,height,and body mass index(P>0.05).Before taping,there was a significant difference in the foot morphological indexes and the areas of the outer front foot,midfoot,and hindfoot between different foot posture groups(P<0.01).(2)Static foot morphological indexes:After taping,there was no statistically significant difference between the groups in navicular drop,arch height flexibility-longitudinal arch,and arch height flexibility-transverse arch(P>0.05),while there was still a significant difference between the groups in the arch height index(P<0.05).In the supination foot group,the arch height index increased slightly,but there was no significant difference before and after taping(P>0.05).In the pronation foot group,the navicular drop and arch height flexibility-longitudinal arch was significantly reduced,and the arch height index was increased.There was a significant difference before and after taping(P<0.05).(3)The index of plantar pressure during walking:After taping,there was no significant difference between the three groups in the area of lateral forefoot and medial midfoot(P>0.05).In the pronation foot group,the lateral load of the forefoot increased after taping(P<0.05).In the supination position group,the load of the lateral forefoot and midfoot regions increased significantly(P<0.05),while the difference in the rear foot region was not significant(P>0.05).(4)The index of plantar pressure during jogging:After taping,there was no statistically significant difference between groups in the lateral forefoot(P>0.05).In the pronation foot group,the load of the medial forefoot increased significantly(P<0.05).In the supination position group,the load of the lateral forefoot,the middle foot and the rear foot region increased significantly(P<0.05).(5)The results showed that the Fascia taping was suitable for different foot postures.It could not only correct the static foot structure of subjects with different foot postures,but also regulate the abnormal plantar pressure distribution during the dynamic activities of walking and jogging,and the load of the midfoot,forefoot,and hindfoot in the supination and pronation posture tended to normal foot posture load level.

BACKGROUND:With social progress,the incidence rate of knee osteoarthritis is getting higher and higher in the face of the rapidly developing aging problem in the social population,and the number of total knee replacement operations is gradually increasing. OBJECTIVE:To study the relationship between prosthesis size and stress shielding by improving the tibial prosthesis base. METHODS:A female patient with severe knee osteoarthritis was selected.Based on Mimics,through extracting the bone structure of the knee joint and simulating the total knee replacement surgery,osteotomy,positioning,and implantation operations were carried out to establish the geometric modeling of the total knee replacement prosthesis(including the femoral prosthesis,tibial bracket,and tibial pad),and improve the design of the tibial prosthesis base,analyze the effect of different tibial prosthesis bases on stress shielding of surrounding bone tissue. RESULTS AND CONCLUSION:(1)Compared with single-stem tibial intramedullary stem prosthesis,the design of four-post tibial intramedullary stem prosthesis created a certain degree of stress shielding around the short stem.However,compared with a thicker single long stem,this stress shielding effect was significantly reduced,and the load was evenly distributed among the four short stems,so there was no stress concentration at the bottom of the pile.(2)The design with a rectangular hole in the middle not only provided relatively good stability,but also helped to reduce stress shielding of cancellous bone to a certain extent,with a reduction rate of 77.5%.(3)Compared with a single-stem tibial intramedullary stem prosthesis,both the four-post tibial intramedullary stem prosthesis and the four-post tibial intramedullary stem prosthesis with a hole in the middle have good stability,which can reduce stress shielding to a certain extent without causing stress concentration,providing theoretical guidance for the design of the tibial intramedullary stem.

BACKGROUND:During stair walking,different muscles work in concert and compensate for each other,and it is unclear whether weakened muscle strength actually affects stair fall risk in older adults.Real-time electromyographic signals from older adults during stair walking are used to reflect high fall risk in older adults during stair walking,which may further improve the accuracy of prediction methods. OBJECTIVE:To investigate the effects of aging on lower limb muscle activation in older adults during stair walking and to analyze the relationship between their muscle activation characteristics and stair fall risk. METHODS:Subjects were divided by age into an older group(n=19)and a younger group(n=18)group and were asked to walk on a 10-step staircase at a natural speed,incorporating surface electromyography acquisition technology,to capture surface electromyography signals during stair walking and calculate the root mean square(RMS)to analyze differences in muscle activation levels.Logistic regression analysis was utilized to establish a predictive model for stair fall risk in older adults by incorporating the lateral femoral and gastrocnemius muscle RMS.The discrimination of the model was evaluated by the receiver operating characteristic curve and area under the curve,and the fit of the model was evaluated using the Hosmer-Lemeshow test RESULTS AND CONCLUSION:Activation of the rectus femoris(Z=-3.464,P=0.001;t=3.379,P=0.002)and lateral gastrocnemius muscle(Z=-2.978,P=0.003;Z=-3.555,P<0.001)was higher in older adults than in younger adults when walking up and down stairs.Activation of the anterior tibialis(Z=-2.350,P=0.019)and medial(Z=2.321,P=0.020)and lateral(t=3.158,P=0.004)gastrocnemius muscles was higher in older adults when ascending stairs than descending stairs.Older adults at risk for falls had less activation of the lateral femoral muscle(Z=-2.613,P=0.009),medial gastrocnemius muscle(Z=-2.286,P=0.022)when walking upstairs,and lateral femoral muscle(Z=-2.368,P=0.018)when walking downstairs than did older adults not at risk for falls.The predictive ability,goodness of fit,and discrimination of the stair fall prediction model for older adults based on surface electromyography were good(P-value of 0.010 for the Omnibus test of the model coefficients,P-value of 0.214 for the Hosmer-Lemeshow test,and the area of the curve of the upper staircase lateral femoral muscle=0.856,P=0.009).(5)The model was modeled with a cut-off value of 38.64 for the upper staircase lateral femoral muscle RMS value and there was a 0.952-fold increase in the risk of staircase falls for each unit decrease in the upper staircase lateral femoral muscle RMS in older adults.

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.

Objective:To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH).Methods:This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children′s hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate.Results:Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive.Conclusions:For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Purpose To explore the additional value of apparent diffusion coefficient(ADC)histogram in predicting extraprostatic extension(EPE)of prostate cancer.Materials and Methods Consecutive patients undergoing multi-parameter MRI and subsequent radical prostatectomy from January 2021 to December 2022 were retrospectively included in this study.Two radiologists independently estimated EPE by using national cancer institute grading system for extraprostatic extension(EPE grade system),with disagreement resolved by discussion.Histogram metrics were derived from three-dimensional volumes of interest encompassing the entire lesion on ADC maps using FireVoxel,obtaining mean ADC,1st,5th,10th,25th,50th,75th,90th,95th and 99th ADC values.The ADC histograms between the groups with and without EPE were compared.Multivariable Logistic regression analysis was used to identify the independent predictive factors of EPE,and a combined model was developed.Receiver operator characteristic curve was used to evaluate the diagnostic performance,and the area under the curve was calculated and compared.Results Thirty-four patients(34％)had pathologic confirmed EPE after radical prostatectomy.ADC histogram parameters showed significant differences between patients with and without EPE(P＜0.05).Multivariate Logistic regression analysis revealed 99th ADC(OR=0.609,P=0.008)and EPE grade system(OR=4.158,P＜0.001)were independent predictors of EPE.For predicting EPE,the area under the curve of 99th ADC,EPE grade system and the combined model were 0.756,0.805 and 0.856,respectively.The area under the curve of 99th ADC and the EPE grade system in identifying EPE showed no significant difference.The diagnostic efficacy of combined model was significantly superior to that of 99th ADC or EPE grading system(Z=2.223,2.208,both P＜0.05).Conclusion The ADC histogram parameters demonstrate additional value for preoperative prediction of EPE.Combining the 99th ADC histogram parameter with the EPE grade system may improve the diagnostic efficacy of EPE.