OBJECTIVE: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. METHODS: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. RESULTS: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. CONCLUSION These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

Objective:To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers.Methods:This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two‐thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left‐sided colon cancers (LCCs). Clinicopathological features were compared using the χ 2 test or Mann‐Whitney U test. Survival was estimated by Kaplan‐Meier curves and the log‐rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results:The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ 2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m 2 vs. 23.2 [21.3, 25.5] kg/m 2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ 2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ 2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ 2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow‐up time for all patients was 48 (range 33, 59) months. The log‐rank test revealed no significant differences in disease-free survival (DFS) ( P=0.668) or overall survival (OS) ( P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204?0.862, P=0.018), whereas a higher proportion of T3‐4 (HR=2.178, 95%CI: 1.089?4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443?3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115?3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146?0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103?1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log‐rank test revealed no significant differences in DFS ( P=0.343) or OS ( P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS ( P=0.047) and OS ( P=0.040) than did patients with pMMR. Conclusions:Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

Objective:To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC).Methods:The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan–Meier method was used for survival analysis.Results:We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4–112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2–21.8) months.Conclusion:The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

Chromosomal karyotyping analysis has been considered as the gold standard for cytogenetic diagnosis and an effective measure for preventing birth defects. However, conventional karyotyping analysis relies heavily on manual recognition, which is time-consuming and labor-intensive. The application of an efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system in clinical practice can significantly reduce the analysis time and greatly improve the efficiency, increase the detection rate for low-percentage mosaicisms, and promote homogenization between laboratories. This can effectively enhance the capacity and level of cytogenetic diagnosis. With the continuous application of such system in the field of karyotyping analysis, a substantial amount of clinical application data and experience has been accumulated. This consensus has been formulated after multiple rounds of discussion by experts from the clinical application collaboration group of the efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system. It aims to provide a reference for peers to better utilize intelligent auxiliary diagnosis systems during chromosomal karyotyping analysis and promote the standardized development of karyotyping analysis technology.

Objective To explore the current situation of the clean operating rooms in Guangdong provincial hospitals of traditional Chinese medicine or integrated Chinese and western medicine to provide references for standardizing the construc-tion of the clean operating room.Methods A questionnaire was designed according to GB 50333-2013 Architectural technical code for hospital clean operating department and WS/T 368-2012 Management specification of air cleaning technique in hospitals,and a questionnaire survey and field investigation were conducted from March to October 2021 on the operating rooms of 64 secondary and above hospitals of traditional Chinese medicine or integrated Chinese and western medicine in Guangdong province,which involved in the basic situation of the operating rooms,general requirements for constructing clean operating rooms,requirements for the layout of clean operating rooms and architectural decorations of the clean operating rooms.Results Of the 64 hospitals surveyed there were 51 ones(79.7％)with clean operating rooms.Tertiary hospitals were mainly equipped with Class Ⅲ clean operating rooms(45.8％),secondary hospitals were provided with general operating rooms(35.0％)and Class Ⅲ clean operating rooms(29.2％),and the differences in the types and classes of the operating rooms in levels of hospitals were statistically significant(P＜0.001).The proportions of tertiary hospitals configured with clean operating rooms and the highest configuration of Class I clean operating rooms were also significantly higher than those of secondary hospitals(94.3％vs 62.1％and 88.6％vs 44.8％,respectively),with statistically significant differences(P＜0.05).There were 66.7％hospitals equipped with negative pressure operating rooms;more than 1/2(56.9％)of the hospitals had the service time of their clean operating rooms longer than 10 years.All the tertiary hospitals did not have air shower rooms in their walkways,while 16.7％secondary hospitals did,with the difference being statistically significant(P＜0.05).Most of the building decorations of clean operating rooms in all the hospitals complied with the specifications(compliance rate＞80.0％),and the difference was not statistically significant between the secondary and tertiary hospitals(P＞0.05);the compliance rate of the decrations of the tertiary hospitals was 78.8％for the requirements of general principle,which was obviously lower than that of the secondary hospitals(100％),with the differences being statistically significant(P＜0.05).Conclusion The clean operating rooms in Guangdong provincial hospitals of traditional Chinese medicine or integrated Chinese and western medicine behave well in configuration,while have some defficiencies in general requirements,layout and building,and necessary guidance,supervision and management have to be involved in to standardize the construction of clean operating rooms.[Chinese Medical Equipment Journal,2024,45(10):77-83]

Objective:To investigate the influence of computer tomography (CT) examination bony parameters and surgical methods on difficult pelvis and perioperative efficacy of mid-low rectal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 191 patients who underwent robotic or laparoscopic total mesorectal excision (TME) for mid-low rectal cancer in the First Affiliated Hospital of Nanchang University from January 2021 to December 2022 were collected. There were 123 males and 68 females, aged (60±11)years. According to the surgical difficulty score, 191 patients were divided into the difficult pelvis group of 41 patients and the non-difficult pelvic group of 150 patients. Thirteen pelvic parameters were obtained on CT images of the 191 patients. Observation indicators: (1) comparison of intraoperative and postoperative conditions of patients in the difficult pelvis group and the non-difficult pelvis group; (2) analysis of factors affecting difficult pelvis in patients with mid-low rectal cancer; (3) stratified analysis of different surgical methods for patients with difficult pelvis. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate and multivariate analyses were conducted using the Logistic regression model. Results:(1) Com-parison of intraoperative and postoperative conditions of patients in the difficult pelvis group and the non-difficult pelvis group. There were significant differences in operation time, volume of intra-operative blood loss, sum of the product of the longest diameters (SPD) of tumor lesions, postopera-tive complications, duration of postoperative hospital stay, and hospitalization expenses between the two groups ( t=-4.853, -5.816, Z=2.838, χ2=81.498, t=-5.897, -2.770, P<0.05). (2) Analysis of factors affecting difficult pelvis in patients with mid-low rectal cancer. Results of multivariate analysis showed that gender, age, pelvic inlet, distance between the sacral promontory and the coccyx, depth of the pelvis, line AB, angle A, and angle B were independent factors affecting difficult pelvis in patients with mid-low rectal cancer ( odds ratio=0.080, 1.067, 3.065, 0.004, 10 165.062, 0.019, 0.476, 0.662, 95% confidence interval as 0.016-0.409, 1.008-1.130, 1.388-6.767, 0.001-0.024, 477.574-216 361.071, 0.003-0.131, 0.358-0.632, 0.551-0.794, P<0.05). (3) Stratified analysis of different surgical methods for patients with difficult pelvis. ① Comparison of general preoperative data of patients with difficult pelvis receiving different surgical methods. Of the 41 mid-low rectal cancer patients with difficult pelvis, 15 underwent robotic TME, and 26 underwent laparoscopic TME. There was a significant difference in the body mass index between patients receiving the two surgical methods ( t=-2.055, P<0.05). ② Comparison of intraoperative and postoperative conditions of patients with difficult pelvis receiving different surgical methods. There was no significant difference in operation time, volume of intraoperative blood loss, SPD of tumor lesions, number of lymph nodes dissected, number of lymph node metastases, distance between tumor and anal verge, combined organ resection, postoperative complications, duration of postoperative hospital stay, hospitalization costs, T staging, N staging, M staging, vascular tumor thrombus, and nerve invasion ( P>0.05). Conclusions:Gender, age, pelvic inlet, distance between the sacral promontory and the coccyx, pelvic depth, AB line, angle A, and angle B are independent factors affecting difficult pelvis in patients with mid-low rectal cancer. There is no difference in perioperative outcomes between mid-low rectal cancer patients of difficult pelvis who received robotic surgery and laparoscopic surgery.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Objective·To establish a prognostic model for the overall survival(OS)of hepatocellular carcinoma(HCC)based on mitochondrial genes and clinical information.Methods·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas(TCGA)database.The nuclear-encoded mitochondrial genes(NEMGs)were obtained from the MitoCarta3.0 database.The"DESeq2"R package and univariate Cox analysis were used to select NEMGs[ubiquinol cytochrome C reductase hinge protein(UQCRH),ATP citrate lyase(ACLY),phosphoenolpyruvate carboxykinase 2(PCK2),Bcl-2 homologous antagonist/killer1(BAK1),Bcl-2-associated X protein(BAX)and Bcl-2/adenovirus E1B interacting protein 3-like(BNIP3L)]in HCC that were associated with OS of HCC and participated in dysregulation of oxidative phosphorylation,tricarboxylic acid cycle and cell apoptosis.Multivariate Cox analysis was applied to select independent risk factors for OS of HCC.A comprehensive prognostic model and a prognostic nomogram with 6-NEMG risk characteristics and TNM staging were established.By using the median of prognostic scores as a cut-off,HCC patients were classified into low-risk and high-risk group.Kaplan-Meier survival curve analysis was conducted and log-rank test was performed to evaluate the survival rates between the low-risk and high-risk group.The area under the curve(AUC)values of receiver operating characteristic(ROC)curve were calculated via using the"timeROC"package.The prognostic model for HCC was validated by using the GEO HCC cohort(GSE14520)for 1,3 and 5 years.Finally,the relative expression level of 6-NEMG was validated in 34 clinical samples of HCC from Xinhua Hospital,Shanghai Jiao Tong University School of Medicine by using real-time quantitative polymerase chain reaction(qPCR)method.Results·Compared to 6-NEMG risk signature only(AUCs for 1,3 and 5 years were 0.77,0.66 and 0.65,respectively)or TNM stage only(AUCs for 1,3 and 5 years were 0.66,0.67 and 0.63,respectively),ROC curve analysis showed that this integrated prognostic model displayed better predictive performance for 1-year(AUC,0.78),3-year(AUC,0.73)and 5-year(AUC,0.69)OS of HCC.The Kaplan-Meier survival curve analysis showed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group(P=0.001).In addition,predictive performance of the prognostic model(AUC for 1,3 and 5 years is 0.67,0.66 and 0.74,respectively)and prognostic differences between the high-risk and low-risk group(P=0.001)were further validated in GEO(GSE14520)external cohort,and these results were consistent with the TCGA data.In addition to BNIP3L,dysregulation of five other NEMGs in the clinical HCC cohort was validated.The correlation analysis in GSE14520 and HCC clinical cohort showed a positive correlation between prognosis score and the size and number of tumors.Conclusion·A new prognostic model that combines 6-NEMG risk characteristics with TNM staging for predicting OS in HCC patients was constructed and validated.This model may help improve the prognosis prediction of HCC patients.