ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective:To investigate the survival outcomes and prognostic factors of patients with double primary breast cancer (BC) and endometrial cancer (EC).Methods:A retrospective cohort study was conducted using data for the period 1992-2018 from the Surveillance, Epidemiology, and End Results (SEER) database. There were 3 465 patients with BC as the first primary cancer (BC-EC group) and 2 804 patients with EC as the first primary cancer (EC-BC group). Kaplan-Meier analysis and cumulative incidence function were used to estimate overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively. Cox regression and Fine-Gray regression were used to analyze the prognostic factors of overall mortality, breast cancer-specific mortality, and endometrial cancer-specific mortality, respectively.Results:During a median follow-up of 160 months, 1 616 deaths occurred in the BC-EC group, with EC being the leading cause of death (37.69%); 994 deaths occurred in the EC-BC group, with BC being the leading cause of death (28.77%). Cox regression identified patients with older ages at first primary cancer diagnosis (54-61 years: HR=1.46, 95% CI: 1.26-1.69; 62-68 years: HR=2.64, 95% CI: 2.29-3.03; ≥69 years: HR=4.89, 95% CI: 4.27-5.60), shorter time interval between the diagnoses (0-5 months: HR=6.13, 95% CI: 5.21-7.21; 6-23 months: HR=5.69, 95% CI: 4.95-6.55; 24-59 months: HR=3.44, 95% CI: 3.04-3.89; 60-119 months: HR=2.32, 95% CI: 2.07-2.59), mixed ductal-lobular BC ( HR=1.29, 95% CI: 1.11-1.48), endometrial mixed cell adenocarcinoma ( HR=1.23, 95% CI: 1.01-1.50), advanced tumor grade (grade Ⅱ BC: HR=1.13, 95% CI: 1.01-1.27; grade Ⅲ BC: HR=1.24, 95% CI: 1.10-1.41; grade Ⅱ EC: HR=1.19, 95% CI: 1.06-1.33; grade Ⅲ EC: HR=1.68, 95% CI: 1.48-1.90), advanced tumor stage of the two cancers (distant BC: HR=3.14, 95% CI: 2.50-3.94; regional EC: HR=1.53, 95% CI: 1.36-1.71; distant EC: HR=3.00, 95% CI: 2.59-3.47) had increased risk of overall mortality. Fine-Gray regression showed that compared with BC-EC patients, EC-BC patients had a higher risk of breast cancer-specific mortality [sub-distribution hazard ratio (s HR=1.24, 95% CI: 1.04-1.47], but a lower risk of endometrial cancer-specific mortality (s HR=0.37, 95% CI: 0.30-0.46). Older ages at first cancer diagnosis, shorter intervals between the diagnoses, negative ER and PR status, and advanced BC grades/stages were associated with increased breast cancer-specific mortality ( P＜0.05). Similarly, older ages, shorter intervals, endometrial serous carcinoma/mixed cell adenocarcinoma, and advanced EC grades/stages correlated with elevated endometrial cancer-specific mortality ( P＜0.05). Conclusion:The management of double primary BC and EC patients requires multidisciplinary strategies, with particular attention to patients presenting older ages at first cancer diagnosis, shorter intervals between the diagnoses, and unfavorable tumor characteristics.

Objective To elucidate the functional role and underlying mechanisms of the ribosome biogenesis factor BMS1 in neuroblastoma(NB)cellular proliferation.Methods We utilized the R2 genomics analysis and visualization platform to analyze the correlation between BMS1 expression levels and clinical characteristics of NB children.The BMS1 mRNA level in three human neuroblastoma cells SK-N-BE(2),BE(2)-C,IMR-32 and two normal cells hTERT RPE-1,IMR-90 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).Two distinct small interfering RNA(siRNA)sequences were used to target BMS1 mRNA in NB cells SK-N-BE(2)and BE(2)-C,with normal cells hTERT RPE-1 serving as controls.We used RT-qPCR to quantify the mRNA levels of BMS1 and two key neuroblastoma-associated molecules(MYCN and p53).After transfection with siRNA,cellular proliferation was detected by various experimental approaches:crystal violet staining,real-time cell analysis(RTCA),colony-forming unit assay and immunofluorescence.Results By analyzing two independent neuroblastoma clinical cohorts(GSE85047/NRC-283 and Westermann-144 datasets),it was found that the BMS1 mRNA level in MYCN-amplified NB was significantly higher than that in MYCN-non-amplified NB(P<0.05).Furthermore,the overall survival rate of NB children in the BMS1 high-expression group was decreased(P<0.05).Consistent with these clinical observations,the BMS1 mRNA level in NB cells SK-N-BE(2),BE(2)-C and IMR-32 was significantly higher than that in normal cells hTERT RPE-1,IMR-90(P<0.05).The targeted transient knockdown of BMS1 in NB cell lines SK-N-BE(2)and BE(2)-C resulted in decreased intracellular MYCN mRNA expression levels(P<0.05),significantly reduced cell proliferation capacity and colony-forming ability(P<0.05).Immunofluorescence revealed that the expression of Ki-67,a proliferation marker,was decreased(P<0.05).At the molecular level,RT-qPCR showed that the p53 mRNA level was significantly elevated in the BMS1-knockdown groups(si BMS1-1#and si BMS1-2#)compared with the control group(P<0.05).However,transient knockdown of BMS1 had no significant impact on the proliferative capacity of normal cells hTERT RPE-1.Conclusion BMS1 expression was up-regulated in MYCN-amplified NB and negatively correlated with the prognosis of the NB children.Mechanistically,interfering with BMS1 expression may transcriptionally activate p53 in NB cells,thereby inhibiting their proliferative ability,while having minimal impact on normal cells growth kinetics.These findings suggest that BMS1 serves as an important proliferation driver in NB and is expected to be a promising therapeutic target for NB children,particularly MYCN-amplified pediatric patients.

Frailty and depressive disorders exhibit a high prevalence and comorbidity rate in the elderly population.Their coexistence significantly reduces patients'quality of life,increases the risk of disability and mortality,and substantially exacerbates the socioeconomic burden.Emerging evidence indicates a significant bidirectional causal relationship between frailty and depressive disorders.The underlying comorbid mechanisms may be related to elevated levels of pro-inflammatory cytokines such as C-reactive protein,neutrophils,and white blood cells.Grey matter volume reduces in specific brain regions including the bilateral thalamus and right precentral gyrus.And abnormal hormone secretion,such as cortisol,resulting from the overactivation of the hypothalamic-pituitary-adrenal axis.Exercise interventions demonstrate positive effects in preventing and managing both frailty and depressive disorders,indicating broad application prospects.However,the underlying mechanisms require further validation.In summary,the comorbidity of frailty and depressive disorders in the elderly requires greater attention.Current evidence supports exercise intervention as an effective therapeutic strategy for improving health outcomes in this population.

Objective To explore the correlation between visceral fat area(VFA)and triglyceride-glucose(TyG)index in people with normal body mass index(BMI)based on quantitative CT(QCT).Methods Totally 1 358 healthy adults with normal BMI who underwent QCT body composition measurement were retrospectively enrolled and divided into normal visceral fat group(normal group,VFA＜100 cm2,n=509),mild visceral fat accumulation group(mild group,100 cmn2≤VFA＜150 cm2,n=431)and severe visceral fat accumulation group(severe group,VFA≥150 cm2,n=418)according to VFA measured with QCT.Pearson and Spearman correlation analysis were performed to observe correlations of TyG index with general data and body composition in 20-40,41-60,61-90 years old men and women with normal BMI,respectively.Multiple linear regression analysis was performed to screen the independent impact factors of TyG index in normal BMI people.Results Low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),glutamic-pyruvic transaminase(GPT),VFA and subcutaneous fat area(SFA)of men with normal BMI at different age stages were weakly-lowly positively correlated with TyG index(r=0.143-0.459,all P＜0.05),while high-density lipoprotein cholesterol(HDL-C)were weakly-lowly negatively correlated with TyG index(r=-0.410--0.222,all P＜0.05).LDL-C,VFA and SFA of women with normal BMI at different age stages were weakly-lowly positively correlated with TyG index(r=0.206-0.495,all P＜0.05).GPT,TC,VFA and liver fat content(LFC)were all independent risk factors,while HDL-C was independent protective factor for TyG index in people with normal BMI(all P＜0.05).Conclusion VFA was positively correlated with TyG index in people with normal BMI.Measurement of abdominal body composition based on QCT combined with lipid indexes had certain potential for predicting insulin resistance and relative metabolic diseases in abdominal obese people.

Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

Objective:To propose a novel radiotherapy marking method-the"#"-character method,which aimed at improving the accuracy and repeatability of positioning during radiotherapy.Methods:A specially"cross-shaped"stamp was designed by this study,which consisted of a handheld square base with a"cross-shaped"protrusion.Using this stamp,the extreme positions of end-expiration and end-inspiration were marked respectively at the laser-guided regions on the directly above and bilateral sides of the patient's body,and each position was printed a"+"character.Finally,a"#-shaped"signal was formed,which represented the full range of respiratory motion of patients.The study included two parts:surface displacement caused by respiration was simulated through a three-dimensional(3D)motion platform,which was used to conduct a phantom experiment for anthropomorphic dummy,A randomized controlled study involving 40 patients,who were treated between January and June 2024 at the Department of Radiotherapy,Cancer Hospital,Chinese Academy of Medical Sciences,were conducted.The cohort included 20 patients with breast tumor(Positioning the outer contour by exposing the chest)and 20 patients with thoracic tumor(fixed position of using thermoplastic film).These patients were divided into two groups for comparison,which received respectively the"#-shaped"method and the conventional"+-shaped"method.The cone-beam computed tomography(CBCT)images before treatment were used to compare the influences of the two kinds of marking methods on the positioning errors of patients with breast tumor and patients with thoracic tumor.Then,the statistical analysis was used to assess precision and accuracy of positioning.Results:The result of phantom experiment indicated that the positioning error of the"#-shaped"method was significantly better than that of the"+-shaped"method under various parameters of respiratory movement.Under three kinds of different respiratory cycles(3,4,and 5 seconds)and amplitudes(8,12,and 15 mm),the positioning errors of the"#-shaped"method were respectively(0.15±0.04)cm,(0.19±0.05)cm and(0.35±0.14)cm,while the"+-shaped"method were respectively(0.42±0.16)cm,(0.64±0.28)cm and(0.88±0.37)cm,and the differences were statistically significant(t=8.347,3.416,2.901,P<0.05).The results of actual patients indicated the positioning error[(0.97±0.32)cm]of the"#-shaped"method was significantly lower than[(1.62±0.47)cm]of the"+-shaped"method for patients with breast tumor(Positioning the outer contour by exposing the chest),and the difference was significant(t=3.615,P<0.05).On the other hand,the positioning error[(0.69±0.24)cm]of the"#-shaped"method was significantly lower than[(0.97±0.39)cm]of the"+-shaped"method for patients with thoracic tumor(fixed position of using thermoplastic film),and the difference also was significant(t=1.934,P<0.05).Conclusion:Compared to the conventional"+-shaped"method,the"#-shaped"method appears higher accuracy and repeatability during the positioning process of radiotherapy,which especially is suitable to the treatment for breast tumor and thoracic tumor that need accurately control the influences of respiratory motion.

Objective To study the syntactic impairment characteristics of wh-question comprehension and expression in Chinese non-fluent aphasic patients.Methods The differences in comprehension and expression be-tween 25 non-fluent aphasic patients and 25 normal subjects were tested in the form of sentence-figure matching and elicitation-repetition to analyze syntactic impairment characteristics related to sentence patterns,question objects,and question words.Results The patients with non-fluent aphasia had impaired comprehension and expression of specific interrogative sentences,and the order of correct comprehension was:(active interrogative sentence,object pseudo-split interrogative sentence)＞(subject pseudo-split interrogative sentence,passive interrogative sentence),and the order of correct expression was:active interrogative sentence＞(pseudo-split interrogative sentence,pas-sive interrogative sentence).Conclusion The pattern of impaired comprehension and expression of wh-question was similar in patients with Chinese non-fluent aphasia.The main influences on syntactic structure included the object of questioning(subject-object)and the type of sentence.Obstacles were more pronounced in sentences with wh-move-ment and non-canonical order.

[Objective] To explore the strategy of blood management in patients with massive transfusion in the frigid plateau region. [Methods] The treatment process of a patient with liver rupture in the frigid plateau region was analyzed, and the blood management strategy of the frigid plateau region was discussed in combination with the difficulties of blood transfusion and literature review. [Results] The preoperative complete blood count (CBC) test results of the patient were as follows: RBC 3.14×10¹²/L, Hb 10⁶ g/L, HCT 30.40%, PLT 115.00×10⁹/L; coagulation function: PT 18.9 s, FiB 1.31 g/L, DD > 6 μg/mL, FDP 25.86 μg/mL; ultrasound examination and imaging manifestations suggested liver contusion and laceration / intraparenchymal hematoma, splenic contusion and laceration, and massive blood accumulation in the abdominal cavity; it was estimated that the patient's blood loss was ≥ 2 000 mL, and massive blood transfusion was required during the operation; red blood cell components were timely transfused during the operation, and the blood component transfusion was guided according to the patient's CBC and coagulation function test results, providing strong support and guarantee for the successful treatment of the patient. The patient recovered well after the operation, and the CBC test results were as follows: RBC 4.32×10¹²/L, Hb 144 g/L, HCT 39.50%, PLT 329.00×10⁹/L; coagulation function: APTT 29.3 s, PT 12.1 s, FiB 2.728 g/L, DD>6 μg/mL, FDP 25.86 μg/mL. The patient was discharged after 20 days, and regular follow-up reexamination showed no abnormal results. [Conclusion] Individualized blood management strategy should comprehensively consider the patient’s clinical symptoms, the degree of hemoglobin decline, dynamic coagulation test results and existing treatment conditions. Efficient and reasonable patient blood management strategies can effectively improve the clinical outcomes of massive transfusion patients in the frigid plateau region.

Objective To evaluate the prognostic value of endosomal sorting complex required for transport(ESCRT)-related genes in osteosarcoma(OS)based on bioinformatics.Methods Preprocessing was performed on 88 OS sequencing samples(with 29 death outcomes)downloaded from the TARGET database and 257 patient clinical information.The Cox proportional hazards model was constructed using the survival package to screen ESCRT genes related to the survival.The STRING database was used to construct a protein-protein interaction(PPI)network,and core genes were selected based on PPI.KEGG enrichment analysis was performed on the selected core genes with more than 5 nodes.Lasso regression analysis was applied to identify ESCRT-related genes more closely related to the prognosis of OS patients.Results A total of 1 486 ESCRT-related genes were identified,of which 164 were associated with the survival.CLTC,MYC,INSR,PTPN1,and TNFRSF1A were identified as core genes related to the prognosis of OS patients.OS patients were randomly divided into a training set(n=44)and a validation set(n=44).In the training set,OS patients in the high-risk group had the significantly shorter overall survival than those in the low-risk group(P<0.05),and the similar results were obtained in the validation set(P<0.01).The ROC(receiver operating characteristic)curve showed an AUC of 0.846 in the training set and 0.877 in the validation set.Prognostic survival analysis and differential analysis of core genes revealed no difference in MYC between high-and low-risk groups in the validation set,and no difference in INSR in the training set.In the overall dataset,all prognostic core genes showed significant differences(P<0.05).Survival analysis of core genes using the R package Survival showed significant differences in survival rates for four genes(CLTC,INSR,PTPN1,TNFRSF1A)except MYC(P>0.05).Univariate independent prognostic analysis identified three genes(TNFRSF1A,PTPN1,MYC)associated with OS survival.Multivariate independent prognostic analysis ultimately identified two key genes(TNFRSF1A,PTPN1)as independent factors influencing OS survival prognosis and closely related to OS patient survival.Conclusion A risk scoring model for OS survival prognosis based on the expression of two key genes,TNFRSF1A and PTPN1,was been successfully constructed using bioinformatics and it can provide more options for clinical treatment and survival prognosis assessment of OS.