Acute-on-chronic liver failure （ACLF） is a complex clinical syndrome， and early identification and accurate prognostic evaluation are of great importance for patient treatment and management. In recent years， with in-depth research on the pathogenesis of ACLF， multiple prognostic biomarkers have been proposed and used in clinical practice. This article systematically reviews the research advances in prognostic biomarkers for ACLF from the aspects of clinical predictive models， immunological biomarkers， metabolic biomarkers， genetic and epigenetic biomarkers， microbiome-related biomarkers， and emerging technologies such as artificial intelligence and multi-omics， and it also discusses the value and application prospects of these biomarkers in the prognostic evaluation of ACLF and proposes future research directions， in order to provide a scientific and comprehensive reference for clinicians， guide individualized treatment and management of ACLF patients， and finally improve the clinical outcomes of patients.

OBJECTIVE To investigate the mechanism of anti-colorectal cancer growth and metastasis-related effects of Astraga-lus mongholicus Bunge-Curcuma aromatica-Paridis Rhizoma(Qi-Zhu-Zao)pairing through PERK/eIF2α/ATF4 signaling pathway mediating endoplasmic reticulum stress.METHODS Twenty-four BALB/c male mice were randomly divided into sham-operated group,model group,5-FU(5-fluorouracil)group(25 mg·kg-1),and Qi-Zhu-Zao high dose group(5.85 g·kg-1),Qi-Zhu-Zao low dose group(2.925 g·kg-1)(n=6)to construct a mouse model of colorectal cancer in situ transplantation tumor,and the inter-vention effect of Qi-Zhu-Zao combination on tumor growth was assessed by the change of tumor volume size after 15 days of administra-tion;the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by H&E.Pathological staining was used to eval-uate the effect of Qi-Zhu-Zao combination on the liver and tumor tissues of mice.The changes of MDA,SOD and GSH-Px levels were detected by enzyme-linked immunosorbent assay(ELISA);the expression of PERK/eIF2α/ATF4 signaling pathway and EMT-related proteins were detected by protein immunoblotting(Western blot).RESULTS Compared with the model group,the tumor volume was significantly reduced(P＜0.000 1),liver and spleen metastases were less pronounced in the Qi-Zhu-Zao high-dose group,and his-topathological staining results of liver tissue and tumor produced changes in oxidative stress indicators SOD,MDA,and GSH-Px,up-regulation of ER stress-related proteins p-PERK,p-IF2α,and ATF4,etc.,upregulated the protein expression levels of E-Cadherin,downregulated N-Cadherin,Vimentin,and Snail,and inhibited the EMT process(P＜0.01 or P＜0.05).CONCLUSION In this paper,we investigated the regulatory mechanism related to the inhibition of colorectal cancer growth and metastasis by the combination of Qi-Zhu-Zao trigonal medicine,and demonstrated that it may inhibit the growth and metastasis of colorectal cancer by activating the PERK/eIF2α/ATF4 pathway to induce sustained ER stress and affect the EMT process of colorectal cancer.

Objective: To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. Methods: This study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. Conclusion Positive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Objective:To ascertain the distribution of interventional radiodiagnosis and treatment resources and the current situation of radiological protection in Beijing, standardize the interventional radiodiagnosis and treatment, and promote the implementation of radiation protection regulatory measures.Methods:Various medical institutions at differetn levels that perform interventional radiodiagnosis and treatment in Beijing were identified as the survey objects. With special questionnaires designed, the investigation groups at two levels of municipality and district was established to investigate the basic situation of interventional radiology and occupational health monitoring by the end of 2020. The indexes and parameters were analyzed and evaluated under the relevant national regulations and standards.Results:By the end of 2020, there were 93 medical institutions performing interventional radiology in Beijing, together with 236 digital subtraction angiography machines (DSA) with higher than 800 mA. A total of 135 593 cases of interventional radiological surgical operation were performed. There were 40 hospitals annually performing more than 1 000 cases and 41 hospitals perfoming 10-1 000 cases. There were 3 539 interventional radiological workers, with 99.0% holding radiological worker certificates. The passing rates of occupational health examination, personal dose monitoring and radiation protection training were 96.9%, 99.5% and 95.8%, respectively. A total of 3 532 sets of protective articles were provided for the workers, of which 98.9% were equipped with split or integrated lead clothing, but 6.5% were not equipped with lead protective glasses and 54.9% were not equipped with lead protective gloves.Conclusions:The radiation protection management for the interventional radiodiagnosis and treatment is generally good. However, the regulatory mechanism should be further improved based on the current distribution of interventional radiodiagnosis and treatment resources, with focus on strengthening the occupational health examination, the radiation protection training, and the configuration and use of protective equipment.

Objective:To explore the expression levels and the clinical significance of serum secreted frizzled-related protein 5 (SFRP5) and miR-124-3p in patients with hypertension during pregnancy.Methods:Ninety-eight patients with hypertension during pregnancy diagnosed from Jan. 2019 to Feb. 2022 were selected as the observation group. According to the degree of the condition of patients, they were divided into 41 cases of pregnancy hypertension, 32 cases of mild preeclampsia, and 25 cases of severe preeclampsia, and 80 healthy subjects during the same period were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression level of serum SFRP5 in patients, real-time fluorescence quantitative method (qRT-PCR) was used to detect the expression level of miR-124-3p. The relationship between SFRP5, miR-124-3p levels and clinicopathological indicators in patients with hypertension in pregnancy was analyzed, Pearson correlation analysis was used to analyze the correlation between SFRP5 and miR-124-3p. Multivariate Logistic regression was used to analyze the risk factors of hypertension in pregnancy.Results:Compared with the control group, the serum SFRP5 expression level of the observation group [ (33.78±5.21) ng/L vs (43.34±8.56) ng/L] was down-regulated, while the miR-124-3p level [ (2.16±0.41) vs (1.01±0.17) ] was up-regulated, and the serum SFRP5 level of the observation group decreased with the severity of the disease[ (38.43±6.37) ng/L (33.18±5.14) ng/L (26.94±3.38) ng/L], while the level of miR-124-3p increased with the severity of the disease[ (1.62±0.24) (2.19±0.43) (3.01±0.69) ], the difference was statistically significant ( P<0.05) . The expression levels of SFRP5 and miR-124-3p in the serum of patients with hypertension in pregnancy were related to the age, pregnancy, pre-pregnancy BMI, and fasting blood glucose level of patients ( P<0.05) , but not related to the gestational age of patients ( P>0.05) . Bioinformatics TargetScan website showed that SFRP5 and miR-124-3p had binding sites. Pearson correlation analysis showed that SFRP5 and miR-124-3p were negatively correlated ( r=-0.610, P<0.05) . Multivariate Logistic regression analysis showed that SFRP5 was a protective factor for pregnancy-induced hypertension in pregnant women, and miR-124-3p was a risk factor ( P<0.05) . Conclusion:The serum levels of SFRP5 and miR-124-3p are abnormally expressed in patients with hypertension during pregnancy, and there is a certain relationship with the degree of disease. Both are involved in the occurrence and development of hypertension during pregnancy.

Objective To assess the long-term efficacy and adverse effects of three-dimensional radiotherapy (3-DCRT) for elderly patients with esophageal cancer,to investigate the effects of diabetes and hypertension on radiation esophagitis and pneumonitis and to analyze the prognostic factors.Methods A total of 233 patients aged 70 or over with esophageal squamous cell carcinoma were treated with 3-DCRT,and 27 of the patients had type-2 diabetes and 63 had hypertension.Radiation esophagitis and pneumonitis were monitored in patients with or without diabetes and in patients with or without hypertension.Potential prognostic factors were analyzed by Logrank single factor analysis and Cox multivariate analysis.Results The incidences of radiation esophagitis and pneumonitis in grade 3 or over were significantly higher in patients with diabetes than in those without diabetes (Z =-3.762,-2.972;P ＜0.001,0.003).The incidences of radiation esophagitis and pneumonitis in grade 3 or over in patients with hypertension were significantly higher than in those without hypertension (Z =-2.610,-2.209;P =0.009,0.027).The 1-,3 and 5-year overall survival (OS) rates were 70.6％,35.8％ and 23.9％,respectively.The median OS was 23.0 months (95％CI:18.6-27.5).Univariate analysis showed that age (x2 =4.274,P =0.039),T stage (x2=9.376,P 0.025),N-stage (x2=8.504,P=0.014),TNM stage (x2=7.806,P=0.020),gross tumor volume (GTV) (x2 =5.209,P =0.022) and short-term therapeutic efficacy (x2 =25.276,P＜0.001) had influenced OS.Multivariate analysis showed that T-stage (P =0.001),N-stage (P =0.007),TNM stage (P =0.002) and short term therapeutic efficacy (P ＜ 0.001) were independent prognostic factors for OS.Conclusions 3-DCRT achieves favorable long-term efficacy in elderly patients with esophageal cancer.Diabetes and hypertension are potential risk factors for radiation esophagitis and pneumonitis.T-stage,N-stage,TNM stage,and short term therapeutic efficacy are independent prognostic factors.

PURPOSE: Breast cancer is the most commonly occurring cancer among women worldwide, and therefore, improved approaches for its early detection are urgently needed. As microRNAs (miRNAs) are increasingly recognized as critical regulators in tumorigenesis and possess excellent stability in plasma, this study focused on using miRNAs to develop a method for identifying noninvasive biomarkers. METHODS: To discover critical candidates, differential expression analysis was performed on tissue-originated miRNA profiles of 409 early breast cancer patients and 87 healthy controls from The Cancer Genome Atlas database. We selected candidates from the differentially expressed miRNAs and then evaluated every possible molecular signature formed by the candidates. The best signature was validated in independent serum samples from 113 early breast cancer patients and 47 healthy controls using reverse transcription quantitative real-time polymerase chain reaction. RESULTS: The miRNA candidates in our method were revealed to be associated with breast cancer according to previous studies and showed potential as useful biomarkers. When validated in independent serum samples, the area under curve of the final miRNA signature (miR-21-3p, miR-21-5p, and miR-99a-5p) was 0.895. Diagnostic sensitivity and specificity were 97.9% and 73.5%, respectively. CONCLUSION: The present study established a novel and effective method to identify biomarkers for early breast cancer. And the method, is also suitable for other cancer types. Furthermore, a combination of three miRNAs was identified as a prospective biomarker for breast cancer early detection.
Area Under Curve ; Biomarkers ; Biomarkers, Tumor ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Data Mining ; Early Detection of Cancer ; Female ; Genome ; Humans ; Methods ; MicroRNAs* ; Plasma ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity

Objective To observe the long-term prognosis and analyze the predictive factors of esophageal cancer patients treated with three-dimensional radiotherapy.Methods A total of 373 patients with esophageal squamous carcinoma who received three-dimensional radiotherapy were retrospectively enrolled in this study.Among these,231 cases received three dimensional conformal radiotherapy (3D-CRT) and the other 142 received intensity modulated radiotherapy (IMRT);202 cases received radiotherapy alone,and the other 171 received chemoradiotherapy;249 cases received involved-field irradiation(IFI),and the other 124 received elective nodal irradiation(ENI);60 cases received a total radiation dose of 50-60 Gy,and the other 313 received 60-70 Gy.Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS).The Logrank single factor analysis and Cox multivariate analysis were used to evaluate predictive factors of PFS and OS.Results The 1-,3-,5-year OS and PFS were 69.4％,33.7％,22.9％ and 63.8％,32.8％,22.4％,respectively.The median OS and PFS were 22.7 months (95％ CI 18.6-25.4 months) and 19.2 months (95％ CI 16.7-21.3 months) respectively.Univariate analysis showed that age,gender,tumor location,three-dimensional technology (3D-CRT vs.IMRT),chemotherapy,prophylactic irradiation to lymphatic drainage area and irradiation dose did not influence OS and PFS (P ＞ 0.05).T-stage,N-stage,TNM-stage and gross tumor volume (GTV) were significantly correlated to OS and PFS (x2 =5.836-14.526,P ＜ 0.05).The multivariate analysis showed that N-stage and GTV were independent predictive factors of OS and PFS (x2 =5.345-12.216,P ＜0.05).The OS and PFS of patients with two fields of lymph node metastases were worse than those with only one lymph node field metastasis (x2 =4.467,4.169,P ＜ 0.05).Conclusions The long-term efficacy for esophageal cancer patients could be significantly improved through 3D-CRT technology.N-stage and tumor volume were independent prognostic factors of OS and DFS.The number of lymph node metastasis field is significantly related to prognosis.

Objective To investigate the risk factors for acute radiation esophagitis andpneumonitis after radiation therapy in esophageal cancer (EC) patients with diabetes or hypertension.Methods A total of 373 EC patients receiving three dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) were included in this study.Among these patients,42 showed concurrent with diabetes and 99 with hypertension.Radiation esophagitis or pneumonitis in patients with or without diabetes,and with or without hypertension were monitored in the 1-year follow up,respectively.Results The prevalence of grade 1,2,3 and 4 radiation esophagitis in diabetes and non-diabetes patients was 40.5％,38.1％,14.3％,4.8％ and 66.2％,27.8％,2.7％,1.8％,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in diabetes and non-diabetes patients was 31.0％,16.7％,9.5％ and 30.8％,15.7％,1.2％,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with diabetes and was significantly higher than those with non-diabetes (x2 =13.573,12.279,P ＜ 0.05).The prevalence of grade 1,2,3 and 4 radiation esophagitis in hypertension and non-hypertension patients was 49.5％,38.4％,8.1％,3.0％ and 68.2％,25.5％,2.6％,1.8％,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in hypertension and non-hypertension patients were 30.3％,18.2％,5.1％ and 31.0％,15.0％,1.1％,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with hypertension was significantly higher than those with non-hypertension (x2 =5.695、5.422,P ＜ 0.05).Diabetes is an independent risk factor for grade 3 or above acute radiation esophagitis and pneumonitis.Conclusions Diabetes or hypertension might be risk factors for severe radiation esophagitis and pneumonitis in EC patients receiving radiation therapy.

Objective To compare the prognostic factors and adverse effects of elderly patients with esophageal cancer between radiotherapy alone and concurrent chemoradiotherapy. Methods A total of 479 patients with esophageal squamous cell carcinoma aged 70 years or older were analyzed retrospectively at our institute, from January 2008 to December 2017. The patients were divided into radiotherapy alone group ( 359 cases ) and concurrent chemoradiotherapy group ( 120 cases ) . After Propensity Score Matching ( PSM) , data from matched patients with 102 cases in each group was analyzed. The overall survival (OS) rates, the prognostic factors and adverse effects were assessed. Results The 1, 3, 5-year of OS in radiotherapy alone group after PSM were 77. 4％, 40. 1％, 22. 7％, respectively, and median overall survival time (mOS) was 26. 9 months (95％ CI:18. 7 - 35. 2 months). The chemoradiotherapy group after PSM were 79. 5％, 47. 6％, 35. 7％ and 35. 6 months (95％ CI:23. 2-48.0 months), respectively, while there was no significant difference between the groups (P >0. 05). Subgroup analysis showed that the 1, 3, 5-year of OS and mOS of the patients aged 70 -75 years in radiotherapy alone group were 79. 4％, 41. 0％, 26. 2％ and 29. 2 months, respectively. The patients aged 70-75 years in chemoradiotherapy group were 86. 5％, 56. 1％, 47. 6％ and 48. 9 months, respectively. There was statistically significance between the groups after PSM(χ2 =4. 746, P<0. 05). The univariate prognostic analysis showed that the age, T stage, N stage, clinical stage, short-term efficacy and performance status were influencing factors for OS (χ2 =6. 714-42. 900, P<0. 05). The clinical stage and short-term efficacy were independent prognostic factors for OS (χ2 =5. 007 -9. 181, P<0. 05). In addition , the risk of non-tumor related death of the patients aged 75 years or older in the chemoradiotherapy group was higher than those in the radiotherapy alone group(χ2 =5. 630, P<0. 05). The prevalence of toxicities (≥grade 3) including bone marrow suppression, radiation esophagitis and radiation pneumonia in the chemoradiotherapy group were higher than that in the radiotherapy alone group (χ2 =4. 701 -28. 318, P<0. 05). Conclusions Concurrent chemoradiotherapy, compared with radiotherapy alone, may improve the prognosis of patients aged 70-75 years with esophageal squamous cell carcinoma.