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.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To explore the application value and surgical experience of neuroendoscopic resection for pediatric patients with cerebellar tumors.Methods:This was a case series study.The clinical data and outcomes of 30 pediatric patients with cerebellar tumors treated through neuroendoscopic surgery in the Department of Neurosurgery, the Guizhou Hospital of Shanghai Children′s Medical Center and Guizhou Provincial People′s Hospital from January 2021 to January 2024 were retrospectively analyzed.Results:Twenty-six patients underwent total resection, 3 patients underwent subtotal resection, and 1 patient underwent biopsy.Postoperative pathological findings showed 9 cases of medulloblastoma, 3 cases of ependymoma, 17 cases of astrocytoma (5 cases of World Health Organization Grade Ⅰ, 3 cases of Grade Ⅱ, and 9 cases of Grade Ⅲ), and 1 case of cerebellar benign lesion.During the perioperative period, malignant arrhythmia occurred and induced death in 1 case, cerebellar mutism occurred in 12 cases, and ataxia occurred in 22 cases.During the 1-36 months of follow-up, 2 cases developed communicating hydrocephalus at the 2 nd and the 6 th month, respectively, and improved after ventriculoperitoneal shunt; cerebellar mutism was relieved to varying degrees after an average postoperative follow-up period of (115±23) days(46-194 days), and ataxia was alleviated after an average postoperative follow-up period of (127±42) days(27-173 days).Tumors relapsed in 5 cases during the last follow-up. Conclusions:Neuroendoscopy provides an alternative to the microscope for experienced operators to achieve the surgical exposure requirements during the resection of pediatric cerebellar vermis tumors.

Background and Aims:Fine-needle aspiration cytology (FNA) has limitations due to the small sample size obtained,including nondiagnostic specimens,indeterminate cytological results,and false-negative or false-positive results,potentially leading to misdiagnosis or missed diagnoses. The BRAF gene mutation,specifically BRAFV600E,is a specific biomarker for papillary thyroid carcinoma (PTC). However,studies on its diagnostic value in FNA benign high-risk thyroid nodules are limited. This study was conducted to further explore the clinical value of adding BRAFV600E mutation testing in FNA benign thyroid nodules.Methods:A retrospective analysis was conducted on the clinical data of 549 patients who underwent 668 ultrasound evaluations indicating high risk of PTC and were classified as TIRADS categories 4-5 thyroid nodules at the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University from January 2019 to September 2022. All patients underwent surgical treatment,and paraffin pathological examination was performed on resected tissues after surgery. Based on inclusion and exclusion criteria,84 FNA benign thyroid nodules were included in this study. The clinicopathologic characteristics of nodules with BRAFV600E mutations were analyzed. Using postoperative pathology as the gold standard,the diagnostic performance of BRAFV600E mutation testing in FNA benign nodules was assessed. Results:Among the 84 FNA benign thyroid nodules,44 (52.4％) tested positive for the BRAFV600E mutation. Patients with BRAFV600E-positive nodules were more likely to be younger than 45 years (56.8％ vs. 35.0％,P=0.045),and their nodules had a smaller median long diameter compared to the BRAFV600E-negative group (0.49 cm vs. 0.61 cm,P=0.024). Postoperative pathology revealed 63 PTC nodules and 21 benign nodules. PTC nodules had a smaller median long diameter than benign nodules (0.50 cm vs. 0.70 cm,P=0.004) and a higher proportion of nodules<1 cm (95.2％ vs. 71.4％,P=0.007),with a higher BRAFV600E mutation rate (68.3％ vs. 4.8％,P<0.001). In terms of the ultrasound characteristics of thyroid nodules,BRAFV600E-positive nodules showed a significantly higher rate of blurred/irregular margins than the negative group (86.4％ vs. 60.0％,P=0.006). Similarly,PTC nodules showed a higher rate of blurred/irregular margins compared to benign nodules (81.0％ vs. 52.4％,P=0.010). Multivariate Logistic regression analysis indicated that BRAFV600E-positive thyroid nodules had a 39.184-fold higher risk of being diagnosed as PTC compared to BRAFV600E-negative nodules (P=0.001),with BRAFV600E mutation being an independent risk factor for PTC diagnosis. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of BRAFV600E mutation testing for PTC diagnosis were 69.3％,95.2％,97.7％,50.0％,and 75.0％,respectively. Conclusion:BRAFV600E mutation testing demonstrates high positive predictive value and accuracy,and can reduce the risk of missed PTC diagnoses among FNA-reported benign thyroid nodules. It is recommended that thyroid nodules with highly suspicious ultrasound features and TIRADS categories 4-5 undergo combined FNA and BRAFV600E mutation testing.

Background and Aims:Fine-needle aspiration cytology (FNA) has limitations due to the small sample size obtained,including nondiagnostic specimens,indeterminate cytological results,and false-negative or false-positive results,potentially leading to misdiagnosis or missed diagnoses. The BRAF gene mutation,specifically BRAFV600E,is a specific biomarker for papillary thyroid carcinoma (PTC). However,studies on its diagnostic value in FNA benign high-risk thyroid nodules are limited. This study was conducted to further explore the clinical value of adding BRAFV600E mutation testing in FNA benign thyroid nodules.Methods:A retrospective analysis was conducted on the clinical data of 549 patients who underwent 668 ultrasound evaluations indicating high risk of PTC and were classified as TIRADS categories 4-5 thyroid nodules at the Thyroid Surgery Department of China-Japan Union Hospital of Jilin University from January 2019 to September 2022. All patients underwent surgical treatment,and paraffin pathological examination was performed on resected tissues after surgery. Based on inclusion and exclusion criteria,84 FNA benign thyroid nodules were included in this study. The clinicopathologic characteristics of nodules with BRAFV600E mutations were analyzed. Using postoperative pathology as the gold standard,the diagnostic performance of BRAFV600E mutation testing in FNA benign nodules was assessed. Results:Among the 84 FNA benign thyroid nodules,44 (52.4％) tested positive for the BRAFV600E mutation. Patients with BRAFV600E-positive nodules were more likely to be younger than 45 years (56.8％ vs. 35.0％,P=0.045),and their nodules had a smaller median long diameter compared to the BRAFV600E-negative group (0.49 cm vs. 0.61 cm,P=0.024). Postoperative pathology revealed 63 PTC nodules and 21 benign nodules. PTC nodules had a smaller median long diameter than benign nodules (0.50 cm vs. 0.70 cm,P=0.004) and a higher proportion of nodules<1 cm (95.2％ vs. 71.4％,P=0.007),with a higher BRAFV600E mutation rate (68.3％ vs. 4.8％,P<0.001). In terms of the ultrasound characteristics of thyroid nodules,BRAFV600E-positive nodules showed a significantly higher rate of blurred/irregular margins than the negative group (86.4％ vs. 60.0％,P=0.006). Similarly,PTC nodules showed a higher rate of blurred/irregular margins compared to benign nodules (81.0％ vs. 52.4％,P=0.010). Multivariate Logistic regression analysis indicated that BRAFV600E-positive thyroid nodules had a 39.184-fold higher risk of being diagnosed as PTC compared to BRAFV600E-negative nodules (P=0.001),with BRAFV600E mutation being an independent risk factor for PTC diagnosis. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of BRAFV600E mutation testing for PTC diagnosis were 69.3％,95.2％,97.7％,50.0％,and 75.0％,respectively. Conclusion:BRAFV600E mutation testing demonstrates high positive predictive value and accuracy,and can reduce the risk of missed PTC diagnoses among FNA-reported benign thyroid nodules. It is recommended that thyroid nodules with highly suspicious ultrasound features and TIRADS categories 4-5 undergo combined FNA and BRAFV600E mutation testing.

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

OBJECTIVE: To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision. METHODS: In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients. RESULTS: The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively. CONCLUSION The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.
Humans ; Quality of Life ; Minimal Clinically Important Difference ; Treatment Outcome ; Constipation/therapy* ; Acupuncture Therapy

ObjectiveTo investigate the perioperative safety and complications of radical cystectomy （RC）. MethodsThe clinicopathological indexes， postoperative complications and prognosis of patients who underwent RC at Sun Yat-sen University Cancer Centre from January 2001 to August 2020 were retrospectively collected and analyzed. Among them， patients from 2011 to 2020 were further analyzed and compared according to the open surgery group （ORC）， laparoscopic group （LRC） and robot-assisted laparoscopic group （RARC）. Independent sample t test， Chi-square test， K-M survival curve and other statistical methods were used to describe the complications and prognosis of patients， and Logistic regression was used to analyze the influencing factors of complications of RC. ResultsAmong the 1041 patients who underwent RC surgery from 2001 to 2020， the median age was 63 （55-69） years. In terms of the gender ratio， men were the majority at 86 percent. Compared with that of the first 10 years， the complication rate of the second 10 years decreased significantly （37.4% vs. 26.7%）. Complications of 667 patients who underwent RC surgery were analyzed from 2010 to 2020， with a median follow-up of 34 months. A total of 415 patients were enrolled in the ORC group， 161 in the LRC group， and 91 in the RARC group. Ileal conduit （659 cases， 63.3%） accounted for the highest proportion of all urinary diversion methods， while orthotopic neobladder accounted for the second （343 cases， 32.9%）. The incidence of all grade complications was 30.5%， and the most common complication was urinary complications. The incidence of total complications and grade ≥3 complications in the ORC group was higher than that in the LRC and RARC groups （Total complications： ORC， 30.8%； LRC，21.1%， RARC，24.2%； P=0.047； Grade ≥3 complications： ORC， 14.7%； LRC，9.3%； RARC，6.6%； P=0.043）. ConclusionsWith the improvement of surgical techniques and experience， the incidence of recent postoperative complications after radical resection of bladder cancer in our center has decreased. Compared with open surgery， minimally invasive surgery has some advantages in reducing the complication rate.

Circular RNA (circRNA) is a single-stranded circular closed RNA molecule formed from linear RNA through reverse splicing. circRNAs are stable, highly conserved, and tissue-specific. circRNAs can regulate physiological and pathological processes through various mechanisms such as formation of competing endogenous RNA and interaction with binding proteins. It has been recently revealed that circRNAs can be translated into peptides and proteins to participate in the initiation and development of cancer. circRNAs are promising diagnostic and prognostic markers for human cancers as well as potential drug targets for cancer therapy. This review summarized the research progresses related to circRNA-encoded peptides and proteins in a variety of cancers. These peptides and proteins are translated through two different mechanisms that depend on internal ribosome entry site and m6A, respectively. We also summarized the potential use of circRNA-encoded peptides and proteins in the diagnosis, treatment, prognosis and mechanistic studies of various cancers.
Humans ; Internal Ribosome Entry Sites ; Neoplasms/genetics* ; Peptides, Cyclic ; RNA/genetics* ; RNA, Circular/genetics*