OBJECTIVE To observe the causal association between colorectal cancer and sepsis by means of bidirec-tional two-sample Mendelian randomization(MR).METHODS The Genome Wide Association Study(GWAS)datasets for colorectal cancer and sepsis were retrieved from the GWAS databases between its establishment and Feb.1,2024.MR was carried out for the colorectal cancer and sepsis interacting as exposure and outcome factors.The single nucleotide polymorhpism(SNPs)that were significantly associated with the exposure factors were screened out by setting P as less than 5.0× 10-8,r2 less than 0.001,the genetic distance 10,000 kb.The SNPs that were remarkably associated with the exposure factors were extracted from the GWAS datasets of the outcome variables,the instrumental variable were finally obtained,the inverse variance weighting(IVW)was taken as the main approach for the causal inference.The level pleiotropy was tested by using MR Egger method and MR-PRESSO,the heterogeneity was tested by IVW method and MR-Egger method,the sensitivity was analyzed by leave-one-out method,and the robustness of the result was tested.RESULTS A total of 30 SNPs were screed out by setting the colorectal cancer as exposure factor and the sepsis as outcome variable(F＞10);there was causal as-sociation between the colorectal cancer and the sepsis(OR=28.955,95％CI:1.215 to 690.052,P=0.037).Totally 14 SNPs were screened out by setting the sepsis as exposure factor and the colorectal cancer as treatment variable(F＞10),and there was no causal association between the colorectal cancer and the sepsis(OR=0.999,95％CI:0.997 to 1.002,P=0.674).There was no level pleiotropy in the instrumental variables during the two times of MR analysis;there was no heterogeneity in the instrumental variables,and the result of the MR analysis was robust.CONCLUSION There is causal association between the colorectal cancer and the increases of risk of sepsis.But there is no causal association between the sepsis and the increase of risk of colorectal cancer.

OBJECTIVE To observe the causal association between colorectal cancer and sepsis by means of bidirec-tional two-sample Mendelian randomization(MR).METHODS The Genome Wide Association Study(GWAS)datasets for colorectal cancer and sepsis were retrieved from the GWAS databases between its establishment and Feb.1,2024.MR was carried out for the colorectal cancer and sepsis interacting as exposure and outcome factors.The single nucleotide polymorhpism(SNPs)that were significantly associated with the exposure factors were screened out by setting P as less than 5.0× 10-8,r2 less than 0.001,the genetic distance 10,000 kb.The SNPs that were remarkably associated with the exposure factors were extracted from the GWAS datasets of the outcome variables,the instrumental variable were finally obtained,the inverse variance weighting(IVW)was taken as the main approach for the causal inference.The level pleiotropy was tested by using MR Egger method and MR-PRESSO,the heterogeneity was tested by IVW method and MR-Egger method,the sensitivity was analyzed by leave-one-out method,and the robustness of the result was tested.RESULTS A total of 30 SNPs were screed out by setting the colorectal cancer as exposure factor and the sepsis as outcome variable(F＞10);there was causal as-sociation between the colorectal cancer and the sepsis(OR=28.955,95％CI:1.215 to 690.052,P=0.037).Totally 14 SNPs were screened out by setting the sepsis as exposure factor and the colorectal cancer as treatment variable(F＞10),and there was no causal association between the colorectal cancer and the sepsis(OR=0.999,95％CI:0.997 to 1.002,P=0.674).There was no level pleiotropy in the instrumental variables during the two times of MR analysis;there was no heterogeneity in the instrumental variables,and the result of the MR analysis was robust.CONCLUSION There is causal association between the colorectal cancer and the increases of risk of sepsis.But there is no causal association between the sepsis and the increase of risk of colorectal cancer.

Objective To investigate the effect of early closed reduction and percutaneous Kirschner wire pinning for Gartland type Ⅱ and Ⅲ pediatric supracondylar humerus fractures.Methods Clinical data of 123 children with Gartland type Ⅱ and Ⅲsupracondylar humerus fractures admitted to our hospital from January 2021 to December 2022 were retrospectively analyzed.According to the time from injury to operation,they were divided into early group(≤ 24 h)and delayed group(＞24 h).The perioperative conditions,postoperative complications,fracture healing,and elbow joint functional recovery were compared between the two groups.Results Compared to the delayed group,the early group had less operation time[(22.9±11.3)min vs.(40.3±17.5)min,t=-6.116,P=0.000],less number of intraoperative fluoroscopy[(10.6±4.5)times vs.(17.4±5.5)times,t=-7.471,P=0.000],shorter hospital stay[(3.3±1.0)d vs.(4.2±1.3)d,t=-3.866,P=0.000],and less hospitalization cost[(10 555.0±971.2)yuan vs.(10 972.4±938.9)yuan,t=-2.345,P=0.021].The rate of anatomical reduction in the early group was higher than that in the delayed group[79.0％(60/76)vs.59.6％(28/47),x2=5.354,P=0.021].No serious complications such as vascular and nerve injury,compartment syndrome,ischemic myosclerosis,myositis ossificans,or cubitus varus and valgus occurred in both group after surgery.The incidences of tension blisters[6.6％(5/76)vs.23.4％(11/47),x2=7.265,P=0.007],plaster loosening[22.4％(17/76)vs.40.4％(19/47),x2=4.574,P=0.032],and pin tract infection[2.6％(2/76)vs.14.9％(7/47),x2=4.757,P=0.029]in the early group were lower than those in the delayed group.The fracture union time,and the time to start active and full weight-bearing activities in the early group were earlier than those in the delayed group(P＜0.05).The Flynn elbow joint scores at 3 and 6 months after surgery in the early group were better than those in the delayed group(Z=-3.469,P=0.001;Z=-2.961,P=0.003).Conclusion Early closed reduction and percutaneous Kirschner wire pinning is effective in the treatment of pediatric supracondylar humerus fractures,which can shorten the operation time and hospital stay,reduce the hospitalization cost,lower the incidence of complications,and restore elbow joint function in early stage.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To explore the correlation between the pathogenesis of toxins damaging liver collateral and the incidence of type 2 diabetes mellitus(T2DM)based on the theory of five circuits and six qi.Methods A total of 986 patients with T2DM treated in the Department of Endocrinology and Metabolism at the Affiliated Hospital of Changchun University of Chinese Medicine from February 2019 to October 2023 were selected as the study subjects.The influences of circuit and qi indicators in the theory of five circuits and six qi on the constitutional characteristics of T2DM patients and the role of pathogenesis of toxins damaging liver collateral in the incidence of T2DM were investigated.Results(1)The five-circuit and six-qi analysis showed that the yearly circuit and sitian/zaiquan conditions had no significant effect on the constitutional characteristics of patients with T2DM(P＞0.05).However,dominant circuit,guest circuit,dominant qi and guest qi significantly influenced the constitutional characteristics of patients with T2DM(P＜0.05).For the distribution of circuit-qi indicators at birth among the 986 patients,dominant circuit was predominated by the terminal circuit of taiyang cold-water,guest circuit was characterized by deficient wood circuit or excessive water circuit,dominant qi was predominated by yangming dry-metal,and guest qi was characterized by taiyin damp-earth.(2)The correlation between the pathogenesis of toxins damaging liver collateral and the incidence of T2DM through comparative analysis revealed that the conveying and dispersing function of the liver plays a leading role in maintaining the body's yin-yang balance and ensuring free movement of qi,indicating that the critical role of toxins damaging liver collateral is the key to the incidence of diabetes.Conclusion Circuit-qi indicators have a certain influence on the constitutional characteristics of T2DM patients.The circuit-qi features at birth of the individuals prone to T2DM are as follows:dominant circuit predominated by the terminal circuit of taiyang cold-water,guest circuit characterized by deficient wood circuit or excessive water circuit,dominant qi being yangming dry-metal,and guest qi being taiyin damp-earth.Pathogenesis of toxins damaging liver collateral is closely related to the incidence of T2DM.Therefore,in treatment,the regulatory role of the liver should be emphasized,and liver-soothing herbs should be used based on syndrome differentiation,aiming for holistic treatment of the physique and the spirit and enhancing the therapeutic efficacy.The exploration will provide a new perspective and approach for the treatment of T2DM.

Objective:To reveal the differences in the transcriptome maps of brain tissues in mice subjected to Flash irradiation and conventional dose rate irradiation with electron beams and to explain the biological effect and mechanisms of Flash irradiation from multiple perspectives.Methods:Following the principle of grouping based on approximate body weights, 36 female C57BL/6J mice were divided into three groups, i. e., the control, conventional dose rate irradiation (CONV), and Flash irradiation (Flash) groups, with 12 mice in each group. Both the CONV and Flash groups received a single 15 Gy whole-brain irradiation with 9 MeV electron beams. At 3 d post-irradiation, the whole-brain tissue specimens were collected for hematoxylin-eosin (HE) staining to observe pathological changes. At 1, 3, and 10 weeks post-irradiation, the motion function, cognitive ability, depression level, and spatial memory capacity of the mice were assessed using ethology. At 1 and 10 weeks after behavioral experiments, brain tissue samples were collected and snap-frozen in liquid nitrogen for reference-based transcriptome sequencing. Accordingly, the differences in the transcriptome maps of radiation-induced brain injury between CONV and Flash groups were analyzed.Results:The HE staining-based pathological result revealed that compared to the CONV group, the Flash group exhibited reduced glial cell hyperplasia and inflammatory cell infiltration in brain tissues. Ethological research result at 1 week post-irradiation showed that the CONV group manifested a significantly decreased total traveled distance compared to the control and Flash groups ( t = 5.51, 2.38, P < 0.05) and a significantly increased immobility time compared to the control group ( t = 3.60, P < 0.05). Ethological research result at 3 weeks post-irradiation indicated that compared to the CONV group, the Flash group displayed significantly alleviated cognitive impairment ( t = 3.35, P < 0.05) and reduced depression levels ( t = 2.39, P < 0.05). Ethological research result at 10 weeks post-irradiation demonstrated that the CONV group showed the worst cognitive performance, significantly differing from the control group ( t = 4.53, P < 0.05). Transcriptome sequencing result revealed that besides immune-related pathways, the Flash group also exhibited multiple upregulated metabolic pathways and fibroblast growth factor (FGF)-related pathways compared to the CONV group. Conclusions:Compared to conventional dose rate irradiation, Flash irradiation can effectively alleviate radiation-induced brain injury in mice. This effect is associated with various metabolic pathways (including amino acid metabolism) and FGF-related pathways besides immune pathways.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

BACKGROUND:The combination of traditional Chinese medicine syndrome and semen quality-related parameters can jointly predict the occurrence of abnormal increase in sperm DNA fragmentation index (DFI) and draw a column chart,which can significantly improve clinical practicality and application efficiency,provide a basis for comprehensive evaluation of semen quality in clinical practice,take active intervention measures to improve clinical outcomes,and formulate personalized medical plans.OBJECTIVE:To explore the prediction model and verification of sperm DNA fragments based on traditional Chinese medicine syndrome and semen quality-related parameters.METHODS:Retrospective analysis was made on 420 infertile patients who received traditional Chinese medicine syndrome diagnosis and sperm DNA fragment rate examination in the Department of Traditional Chinese Medicine Andrology,Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2019 to July 2021.According to the Manual of Human Semen Examination and Treatment Laboratories (6th Edition),137 patients with sperm DFI>30％ were included in the group of abnormally high sperm DFI,and 283 patients with sperm DFI ≤ 30％ were taken as the control group.First,univariate analysis was used to screen the influencing factors of the abnormal increase of sperm DFI.Then,the best matching factor was selected by using the collinearity problem of LASSO correction factors.Then,it was included in the multifactor forward stepwise logistic regression to find out its independent influencing factors and draw a nomogram.Finally,the receiver operating characteristic curve,calibration curve,decision curve analysis and clinical impact curve were used to verify the differentiation and accuracy of the prediction model and its clinical application effectiveness.RESULTS AND CONCLUSION:(1) The results of the univariate analysis showed that age,body mass index,forward motion rate,total sperm motility,sperm concentration,sperm morphology,kidney yang deficiency syndrome,damp heat downpour syndrome,and kidney sperm deficiency syndrome were the influencing factors for the abnormal increase of sperm DFI (P<0.05).(2) The best matching factors further screened by LASSO regression were age,body mass index,total sperm motility,sperm concentration,sperm morphology,kidney yang deficiency syndrome,damp heat downpour syndrome,and kidney essence deficiency syndrome (P<0.05).(3) Multifactor forward stepwise Logistic regression showed that age,body mass index,sperm concentration,total sperm motility,damp heat downpour syndrome,and kidney yang deficiency syndrome were six independent factors that caused the abnormal increase in sperm DFI.(4) Receiver operating characteristic curve showed that the area under the curve of the model group was 0.760(0.713,0.806),and the area under the curve of the validation group was 0.745(0.714,0.776).It showed that the prediction model had good discrimination.(5) The average absolute error of the calibration curve was 0.040,and the Hosmer Lemeshow test (P>0.05),suggesting that there was no significant statistical difference between the probability of the abnormal increase in DFI of spermatozoa predicted by the model and the probability of the abnormal increase in DFI of spermatozoa actually occurred,which confirmed that the model had good accuracy.(6) Decision curve analysis and clinical impact curve showed that the model group and validation group had the maximum clinical net benefit when the threshold probability values were (0.08-0.84) and (0.09-0.78) respectively,and had good clinical application efficiency within the threshold probability range.(7) These findings conclude that age,body mass index,sperm concentration,total sperm viability,damp heat downpour syndrome and kidney yang deficiency syndrome are independent factors that cause the abnormal increase in sperm DFI.The nomogram of the clinical prediction model constructed by them has good clinical prediction value and clinical application efficiency,and can provide the basis for comprehensive clinical evaluation of semen quality and individualized medical service.