OBJECTIVE To systematically evaluate risk prediction models for chemotherapy-induced myelosuppression in breast cancer， and provide a scientific reference for clinical healthcare workers in selecting or developing effective predictive models. METHODS A systematic search was conducted for studies on predictive models of the risk of chemotherapy-induced myelosuppression in breast cancer across the CNKI， VIP， Wanfang， PubMed， Web of Science， Cochrane Library， Embase， and Scopus databases， with a time frame of the establishment of the database to May 7， 2024. Literature was independently screened by 2 investigators， data were extracted according to critical appraisal and data extraction for systematic reviews of predictive model studies， and the risk of bias evaluation tool for predictive model studies was used to analyze the risk of bias and applicability of the included studies. RESULTS There were totally 7 studies， comprising 12 models. Among them， 11 models indicated an area under the subject operating characteristic curve of 0.600-0.908； 2 models indicated calibration. The common predictor variables of the included models were age， pre-chemotherapy neutrophil count， pre-chemotherapy lymphocyte count， and pre-chemotherapy albumin. The overall risk of bias of the 7 studies was high， which was mainly attributed to the flaws in the study design， insufficient sample sizes， inappropriate treatment of variables， non-reporting of missing data， and the lack of indicators for the assessment of the models， but the applicability was good. CONCLUSIONS The predictive performance of risk predictive models for chemotherapy-induced myelosuppression in breast cancer remains to be further enhanced， and the overall risk of model bias is high. Future studies should follow the specifications of model development and reporting， then combine machine learning algorithms to develop risk predictive models with good predictive performance， high stability， and low risk of bias， so as to provide a decision-making basis for the clinic.

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

OBJECTIVE To construct a prediction model for the efficacy of serotonin-norepinephrine reuptake inhibitor （SNRI） in inpatients with moderate and severe depression by using a machine learning method. METHODS The case records of inpatients with moderate and severe depression treated with SNRI antidepressants were collected from a third-grade class-A hospital in Xinjiang from January 2022 to October 2024； those patients were divided into effective group and ineffective group based on the Hamilton depression scale-24 score reduction rate. After screening the characteristic variables related to the therapeutic efficacy of SNRI drugs through LASSO regression， five prediction models including support vector machine， k-nearest neighbor， random forest， lightweight gradient boosting machine and extreme gradient boosting were constructed using the training set. Bayesian optimization was used to adjust the hyperparameters of these models. The performance of the models was evaluated in the validation set to select the optimal model. The Shapley additive explanations method was used to perform explainable analysis on the best model. RESULTS The medical records from 355 hospitalized patients with moderate and severe depression were collected， comprising 285 cases in the effective group and 70 cases in the ineffective group， resulting in an overall therapeutic response rate of 80.28%. After feature variable screening， five characteristic variables for therapeutic efficacy were obtained， including Hamilton anxiety scale， blood urea nitrogen， combination of anti-anxiety drugs， drinking history， and first onset of the disease. Compared with other models， the random forest model performed the best. The area under the receiver operating characteristic curve was 0.85， the area under the precision-recall curve was 0.87， the accuracy was 0.74， and the recall rate value was 0.75. CONCLUSIONS The random forest model constructed based on five characteristic variables demonstrates potential for predicting the therapeutic efficacy of SNRI antidepressants in hospitalized patients with moderate and severe depression.

Objective To understand the current status of radiation diagnosis and treatment resources and their use in Taiyuan City, China, and provide data support for optimizing resource allocation and standardizing diagnosis and treatment. Methods A census-based approach was implemented using a standardized questionnaire to collect basic information on radiation diagnosis and treatment institutions in Taiyuan City. The number and use frequency of radiation diagnosis and treatment resources were calculated based on the resident population of Taiyuan City at the end of 2023. Results There were a total of 562 radiation diagnosis and treatment institutions in Taiyuan City, with 3970 workers and 1354 pieces of equipment. The numbers of radiation diagnosis and treatment institutions, workers, and equipment per 1 000 000 population were 103, 728, and 248, respectively. There were significant differences in radiation diagnosis and treatment resources among different districts and counties. There were 526 (93.59%) radiation diagnosis and treatment institutions and 25 (96.15%) tertiary hospitals in the six urban districts. All institutions offering nuclear medicine diagnosis and treatment and radiotherapy were located in the urban districts. There were substantial disparities among hospitals of different levels. The average numbers of radiation workers and equipment were in the order of tertiary hospitals (99.42, 17.15) > secondary hospitals (13.31, 4.62) > primary and unrated hospitals (1.43, 1.38). The frequency of radiation diagnosis and treatment in tertiary hospitals was 112 149 per hospital, which is 5 times that of secondary hospitals and 44 times that of primary and unrated hospitals. The use frequency of radiation diagnosis and treatment was 975.79 per 1000 population. The use frequency was 941.12 per 1000 population for X-ray diagnosis, 21.68 per 1000 population for interventional radiology, 8.70 per 1000 population for nuclear medicine diagnosis, 2.33 per 1000 population for nuclear medicine treatment, and 1.95 per 1000 population for radiotherapy. Conclusion There are abundant radiation diagnosis and treatment resources in Taiyuan City. The use frequency of radiation diagnosis and treatment has reached the level of Class II medical and health care regions, and there remains considerable room for growth and improvement. At present, the distribution of radiation diagnosis and treatment resources and services is unbalanced among different districts and counties as well as among institutions of different levels, mainly concentrated in urban districts and tertiary hospitals. The health administrative department needs to make overall plans and allocate resources scientifically.

OBJECTIVE: To compare the effectiveness of clavicular hook plate fixation in the treatment of acromioclavicular joint dislocation and distal clavicle fractures. METHODS: A clinical data of 90 patients, who underwent clavicular hook plate fixation between January 2014 and June 2023, was retrospectively analyzed. There were 40 patients with distal clavicle fractures (fracture group) and 50 with acromioclavicular joint dislocations (dislocation group). There was no significant difference in the baseline data of gender, age, cause of injury, side of injury, time from injury to operation, and constituent ratio of osteoporosis patients between the two groups ( P>0.05). The time to remove the internal fixators and the occurrence of complications were recorded. Before removing the internal fixator and at 3 months after removing, the visual analogue scale (VAS) score was used to evaluate the degree of pain, and the mobility of the shoulder joint in forward flexion, elevation, and abduction was measured. Before removing the internal fixators, the Constant-Murley score and the University of California, Los Angeles (UCLA) score were used to evaluate the function of the shoulder joint. X-ray films of the shoulder joint were taken during follow-up to observe the occurrence of subacromial osteolysis, acromioclavicular joint osteoarthritis, and distal clavicle bone atrophy. Subgroup comparison was conducted between patients with and without subacromial osteolysis in the two groups. RESULTS: All incisions healed by first intention in both groups. All patients were followed up 1-9 years, with a median of 5 years; the difference in follow-up time between the two groups was not significant ( P>0.05). During follow-up, subacromial osteolysis occurred in 74 cases, including 41 cases of typeⅠand 33 cases of type Ⅱ, distal clavicle bone atrophy in 15 cases, and acromioclavicular joint osteoarthritis in 8 cases. There were significant differences in the removal time of internal fixators, the incidence of bone atrophy, and the incidence of osteoarthritis between the two groups ( P<0.05). There was no significant difference in the incidence of subacromial osteolysis ( P>0.05). Before removing the internal fixators, there was no significant difference in VAS score, UCLA score, and Constant-Murley score between the two groups ( P>0.05), while there were significant differences in shoulder joint range of motion in all directions ( P<0.05). After removing the internal fixators, only the difference in elevation was significant ( P<0.05). Within the group comparison, the VAS score and mobility of shoulder joint in abduction and elevation after removing the internal fixators were significantly superior to those before removing ( P<0.05). In the fracture and dislocation groups, there was only a significant difference in plate length between the subgroup with and without subacromial osteolysis ( P<0.05), while there was no significant difference in the above other indicators ( P>0.05). CONCLUSION Clavicular hook plate is a good choice for treating acromioclavicular dislocation or distal clavicle fractures, but the incidence of subacromial osteolysis is higher, and the degree of bone resorption is more severe in fracture patients. After removal of the internal fixator, the shoulder functions significantly improve. It is recommended to remove the internal fixator as soon as possible within the allowable range of the condition.
Humans ; Clavicle/surgery* ; Acromioclavicular Joint/surgery* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/surgery* ; Male ; Retrospective Studies ; Female ; Adult ; Middle Aged ; Treatment Outcome ; Joint Dislocations/surgery* ; Aged ; Range of Motion, Articular ; Young Adult ; Postoperative Complications

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To explore the candidate genes and potential molecular mechanisms of anti-neutrophil cyto-plasmic antibodies(ANCA)-associated vasculitis by bioinformatics and experimental validation,and to provide a scientific theoretical basis for the treatment of potential inflammatory targets for ANCA-associated vasculitis.Meth-ods The GSE108109 chip data was retrieved from the Gene Expression Omnibus(GEO)database,and the differ-ential genes were processed,analyzed and screened using the R language related program package.Kyoto encyclo-pedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analysis was carried out using DAVID online network cable,and the interaction network of the protein encoded by the selected genes of inflammatory syn-drome was constructed through STRING website.Further endogenous competitive RNA(ceRNA)regulatory net-work was predicted and constructed through miRWalk and DIANA-LncBase databases,and key genes were screened from the network to draw ROC curve.The renal biopsy samples of patients with ANCA-associated vasculi-tis confirmed by our hospital were collected as the experimental group,and the renal biopsy samples of IgA ne-phropathy and micro-adaptive nephropathy were collected as the control group.Immunohistochemical staining was performed on the collected renal biopsy samples,and the average optical density was calculated by semi-quantita-tive analysis of immunohistochemical staining to further verify the expression of the key genes screened by the bioin-formatics analysis.Pearson linear correlation analysis was performed between the average optical density results and the clinical inflammatory data of patients.Results 846 differential genes were screened,of which 444 genes were significantly up-regulated and 402 genes were significantly down-regulated.Through KEGG and GO analysis,im-portant differentially expressed genes related to inflammation regulation were obtained.Among them,CSF1R and TNFRSF1B,two differentially expressed genes never reported in ANCA-associated vasculitis,attracted our atten-tion.At the same time,we constructed multiple ceRNA regulatory axes including KCNQ1OT1-hsa-miR-125a-5p-TNFRSF1B.There were 15 samples of ANCA-associated vasculitis,6 samples of IgA nephropathy,and 3 samples of micropathological kidney.Immunohistochemical results of renal biopsy specimens showed that the expression of CSF1R and TNFRSF1B in ANCA-associated vasculitis kidney tissue was higher than that in the control group.Pearson correlation analysis of clinical data of patients in ANCA group showed that the expression of CSF1R was positively correlated with the content of neutrophil count(r=0.587),and the expression of TNFRSF1B was posi-tively correlated with the content of serum C-reactive protein(r=0.646).Conclusion Key genes related to in-flammatory regulation such as CSF1R and TNFRSF1B were investigated by bioinformatics methods,and a rigorous ceRNA regulatory network was constructed.The expression of CSF1R and TNFRSF1B in ANCA vasculitis was high-er than that in the control group through immunohistochemistry.The results provides a scientific theoretical basis for the molecular mechanism of inflammation,and laid a good foundation for new therapeutic targets of ANCA-related vasculitis for inflammation.

Objective To explore the relationship between body mass index(BMI)and blood pressure(BP),blood lipids,waist-to-hip ratio(WHR),and hemoglobin(Hb)in the elderly.Methods A total of 10 978 elderly individuals aged≥65 years old in a community in Baoshan District,Shanghai from February 2023 to October 2023 were selected as the research subjects.Height,body mass,waist circumference(WC),hip circumference(HC),systolic blood pressure(SBP),diastolic blood pressure(DBP),total cholesterol(TC),high-density lipoprotein(HDL),low-density lipoprotein(LDL),Hb were measured,and BMI and WHR were calculated.According to the Chinese BMI reference standard,the elderly were divided into a lean group(BMI＜18.5 kg/m2,n= 310),a normal body mass group(18.5 kg/m2≤BMI＜24 kg/m2,n=4 692),a overweight group(24 kg/m2≤BMI＜28 kg/m2,n= 4 615),and an obese group(BMI≥28 kg/m2,n=1 361).The levels of BP,blood lipids,WHR,and Hb in the four groups were compared and correlation analysis was conducted.Results The levels of BMI,WC,HC,WHR,SBP,DBP,and Hb in elderly men were higher than those in elderly women(all P＜0.01),while the levels of TC,HDL,and LDL were lower than those in elderly women(all P＜0.01).The differences in SBP,DBP,TC,HDL,LDL,WHR,and Hb among the four groups were statistically significant(all P＜0.05),and BMI was positively correlated with SBP,DBP,TC,LDL,WHR,and Hb(r=0.109,0.064,0.041,0.042,0.108,0.089,all P＜0.01),and negatively correlated with HDL(r=﹣0.106,P＜0.01).The BMI of elderly men in the normal body mass group was higher than that of elderly women,while the BMI of elderly women in the obesity group was higher than that of elderly men(both P＜0.01).In the normal body mass group,the BMI of elderly people aged＜75 years old was higher than that of elderly people aged≥75 years old(P＜0.05).Conclusions BMI is closely related to the health of the elderly,and maintaining an ideal BMI is the foundation for health management and prevention of chronic diseases in the elderly.

Lipid globules in retina and choroid are new definitions based on pathology and high-resolution optical coherence tomography (OCT). OCT examination shows that the lipid globules are low reflective circular cavities in the choroid and retina, without strong reflective boundaries around them, followed by a characteristic superreflective tail. It occurs in healthy human eyes and in age-related macular degeneration characterized by retinal pigment epithelium (RPE) atrophy. Its characteristic superreflective tail is the key to distinguishing it from other diseases. At present, the understanding of lipid globules is still in the initial stage. Although lipid globules can be observed in healthy human eyes, a certain prevalence rate indicates that they are associated with choroidal hypoperfusion and RPE atrophy. In the future, larger randomized controlled trials and longer follow-up time are needed to explore its pathogenesis, pathological characteristics and treatment prognosis.

Objective:To observe the proteomic changes in vitreous fluid samples from patients with rhegmatogenous retinal detachment combined with choroidal detachment (RRDCD).Methods:A prospective cross-sectional clinical study. Vitreous fluid samples were collected from 35 patients with RRDCD (RRDCD group) and 40 patients with rhegmatogenous retinal detachment (RRD group) who were diagnosed at Wuhan Aier Eye Hospital between November 2021 and December 2023. Prior to vitrectomy, 0.3-0.5 ml of vitreous fluid was collected from the affected eyes. Differentially expressed proteins were analyzed using Data-Independent Acquisition (DIA). Three of these proteins were randomly selected for validation using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analyses, including gene ontology functional enrichment and kyoto encyclopedia of genes and genomes pathway enrichment, were performed to explore the functions of the differentially expressed proteins.Results:Significant differences were observed between the RRDCD and RRD groups in intraocular pressure ( t=-12.795), the number of retinal tears ( t=4.601), the extent of retinal detachment ( χ2=39.642), axial length ( t=0.840), postoperative proliferative vitreoretinopathy incidence ( χ2=4.730), single-surgery reattachment rate ( χ2=7.717), and best-corrected visual acuity ( t=7.033) at 6 months postoperatively ( P<0.05). A total of 237 differentially expressed proteins were identified between the RRDCD and RRD groups, with 63 upregulated and 174 downregulated. These proteins were involved in pathways such as extracellular matrix-receptor interaction, complement activation, coagulation, and lysosomal pathways. ELISA validation results showed that the expression trends of the three selected proteins in the RRDCD and RRD groups were consistent with the DIA proteomic analysis. Compared to the RRD group, proteins such as fibrin, coagulation factors, cathepsins, and trypsin inhibitors were significantly upregulated in the RRDCD group. Conclusions:The protein expression profile in vitreous fluid samples from RRDCD patients show significant alterations compared to the RRD group. These differential changes suggest that RRDCD is closely associated with complement and coagulation cascade activation, lysosomal pathways, and extracellular matrix remodeling.