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.

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 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.

Objective:To analyze the compliance with enhanced recovery after surgery (ERAS) protocol in geriatric patients with fresh fracture.Methods:A retrospective study was conducted on the data of the patients with fresh extremity fracture which had been included in the ERAS perioperative protocol database during May 2019 and January 2022 at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital. The patients ≥65 years were selected as a study group which was matched by a control group of the patients < 65 years in sex, fracture type and date frame of hospitalization at a ratio of 1∶1. The 2 groups were compared in the compliance with the 14 ERAS core perioperative elements.Results:The study group and the control group each included 66 patients who were matched in sex and fracture type. 62.1% (41/66) of the patients in the study group had combined diseases, significantly more than that [16.7% (11/66)] in the control group( P<0.001). Altogether, the compliance with the 14 ERAS core perioperative elements was 78.6 (71.4, 85.7) % in both groups, showing no significant difference between them ( P>0.05). Respectively, the compliance with the postoperative oral intake in the study group (80.3%, 53/66) was significantly lower than that in the control group (92.4%, 61/66) ( P<0.05); the compliance with the other 13 elements showed no statistically significant difference between the 2 groups ( P>0.05). Conclusion:The ERAS perioperative protocol can be carried out smoothly in geriatric patients with fresh fracture whose compliance may be comparable to that of the none-elderly patients.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective:To investigate the effects of types of ulnar styloid process fracture on the treatment of distal radius fracture.Methods:The 80 patients were analyzed retrospectively who had been treated at The First Department of Hand Surgery, Honghui Hospital from January 2019 to January 2020 for fracture of distal radius complicated with fracture of ulnar styloid process. They were 25 males and 55 females, aged from 30 to 85 years (average, 58.6 years). According to the types of ulnar styloid process fracture, 40 patients were assigned into a Hauck type Ⅰ group and the other 40 into a Hauck type Ⅱ group. The 2 groups were compared in terms of operation, postoperative complications, hospital stay, bone union, visual analogue scale (VAS) on postoperative 1 to 3 days, and modified Mayo wrist function score, wrist range of motion and quality of life by WHOQOL-BREF at the last follow-up.Results:The 2 groups were comparable because there was no significant difference in age, gender, American Society of Anesthesiologists (ASA) rating, or time from injury to operation between them ( P>0.05). All the patients were followed up for 12 to 24 months (average, 17 months). There was no significant difference between Hauck type Ⅰ group and Hauck type Ⅱ group in operation time, intraoperative blood loss, hospital stay, rate of postoperative complications, fracture union, modified Mayo wrist function score or VAS on postoperative 1 to 3 days ( P>0.05). At the last follow-up, the palm tilt and ulnar inclination angles were 13.8°±1.9° and 21.6°±2.8° in Hauck type Ⅰ group, significantly larger than those in Hauck type Ⅱ group (11.9°±1.6° and 18.8°±2.3°) ( P<0.05). At the last follow-up, Hauck Ⅰ group scored 85.3±6.4,85.6±6.5, 84.7±6.3 and 85.0±6.7 respectively in the domains of physical health, psychology, environment and social relationships, significantly higher than those Hauck type Ⅱ group did (78.5±6.5, 78.9±6.5, 77.8±6.1 and 77.9±6.3) ( P<0.05). Conclusions:In open reduction and internal fixation for distal radius fracture, Hauck Type Ⅰ fracture of ulnar styloid process has no significant effect on the functional recovery of the wrist but Hauck Type Ⅱ fracture of ulnar styloid process may. Therefore, surgical fixation needs to be strengthened if Hauck Type Ⅱ fracture of ulnar styloid process is complicated.

Recent insights collectively suggest the important roles of lysyl oxidase (LysOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms remain elusive. Herein, we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons. Mechanistically, LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) signaling. In addition, overexpression of LysOX via adeno-associated viral vector (AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage. Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile (BAPN) significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage, while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers. These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage. Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.
Antipsychotic Agents ; adverse effects ; Asian Continental Ancestry Group ; genetics ; China ; Genome-Wide Association Study ; Genotype ; Humans ; Lipid Metabolism ; genetics ; Neurosecretory Systems ; drug effects ; Pharmacogenomic Testing ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic ; genetics ; Receptors, Dopamine ; genetics ; Receptors, Histamine ; genetics ; Receptors, Serotonin ; genetics ; Weight Gain ; drug effects ; genetics

in view of the emphasis on disease management and clinical research, the authors introduced the evaluation and construction methods of the departments based on disease management. Introduction to the selection process of the evaluation and construction methods of such departments, the authors expounded the construction thought of clinical research evaluation system. This paper analyzed the important role of clinical scientific research in the formation of hospital characteristic advantage and leading position, then suggested that hospitals should take research-type diseases as the basis, promote steady breakthroughs in their medical services and scientific research level, and fully reflect the responsibilities of tertiary hospitals.