Aim To investigate the role and mechanism of RNA binding protein zinc finger protein 36(ZFP36)in vascular calcification.Methods Human aortic smooth muscle cells were infected with ZFP36-overex-pressing virus or transfected with ZFP36 siRNA,followed by high phosphate stimulation to observe the effect of overex-pression or knockdown of ZFP36 on smooth muscle cell calcification;RNA immunoprecipitation and stability experiments were used to detect whether Runx2 was the target gene of ZFP36;Smooth muscle specific ZFP36 knockout mice were generated and vitamin D was used to induce vascular calcification.Alizarin Red and Von Kossa staining were used to observe calcification of aortic vessels,and Western blot was used to detect Runx2 protein expression.Results ZFP36 expression was elevated under calcification-stimulating conditions.Overexpression of ZFP36 alleviated high phos-phate-induced smooth muscle cell calcification,while knockdown of ZFP36 exacerbated calcification.ZFP36 could bind to Runx2 mRNA and promote its degradation.At the cellular level,ZFP36 could inhibit smooth muscle cell calcification via Runx2.At the animal level,knockout of ZFP36 in smooth muscle exacerbated vascular calcification induced by vita-min D.Conclusion ZFP36 inhibits vascular calcification by targeting Runx2 mRNA and suppressing its expression in smooth muscle cells.

Aim To investigate the role and mechanism of RNA binding protein zinc finger protein 36(ZFP36)in vascular calcification.Methods Human aortic smooth muscle cells were infected with ZFP36-overex-pressing virus or transfected with ZFP36 siRNA,followed by high phosphate stimulation to observe the effect of overex-pression or knockdown of ZFP36 on smooth muscle cell calcification;RNA immunoprecipitation and stability experiments were used to detect whether Runx2 was the target gene of ZFP36;Smooth muscle specific ZFP36 knockout mice were generated and vitamin D was used to induce vascular calcification.Alizarin Red and Von Kossa staining were used to observe calcification of aortic vessels,and Western blot was used to detect Runx2 protein expression.Results ZFP36 expression was elevated under calcification-stimulating conditions.Overexpression of ZFP36 alleviated high phos-phate-induced smooth muscle cell calcification,while knockdown of ZFP36 exacerbated calcification.ZFP36 could bind to Runx2 mRNA and promote its degradation.At the cellular level,ZFP36 could inhibit smooth muscle cell calcification via Runx2.At the animal level,knockout of ZFP36 in smooth muscle exacerbated vascular calcification induced by vita-min D.Conclusion ZFP36 inhibits vascular calcification by targeting Runx2 mRNA and suppressing its expression in smooth muscle cells.

Objective:To observe the efficacy of 3D printing-assisted hematoma puncture and drainage in the treatment of hypertensive intracerebral hemorrhage and to explore the factors affecting postoperative brain dysfunction.Methods:A retrospective Case-control study was conducted to select 168 hypertensive intracerebral hemorrhage patients who were treated with 3D printing assisted hematoma puncture and drainage in the People′s Hospital of Yuechi County from January 2020 to September 2022 as the observation group, and 125 hypertensive intracerebral hemorrhage patients who were treated with CT guided hematoma puncture and drainage in the People′s Hospital of Yuechi County at the same time as the control group. The clinical efficacy of the two groups of patients was compared. According to the occurrence of postoperative brain dysfunction, the patients in the observation group were divided into normal brain function group ( n=121) and brain dysfunction group ( n=47). The clinical data of age, preoperative cerebral hernia, blood loss, ventilator-assisted ventilation, postoperative Glasgow coma index score (GCS) and postoperative complications were compared between the two groups. Multivariate Logistic regression was used to analyze the factors affecting postoperative brain dysfunction in the observation group, and a line chart model was constructed and its predictive efficiency was evaluated. The measurement data of normal distribution is expressed as mean ± standard deviation ( ± s), and independent sample t-test is used for inter group comparison. Chi-square test was used for comparison between count data groups. Results:The proportion of the drainage tube in the hematoma, hematoma clearance rate at 3 and 7 days after surgery, total effective rate of treatment, and GCS score at 1 week after surgery in the observation group were 88.69%(149/168), 54.17%(91/168), 96.43%(162/168), 92.86%(156/168), and 10.72±3.45, respectively, the control group was 75.20%(94/125), 36.80%(46/125), 81.60%(102/125), 76.80%(96/125), and 9.08±3.22, respectively, the difference between the two groups was statistically significant ( P<0.05). Advanced age ( OR=1.983, 95% CI: 1.169-2.732, P=0.017), preoperative cerebral hernia ( OR=1.532, 95% CI: 1.113-2.139, P=0.029), bleeding volume ≥ 50 mL ( OR=2.538, 95% CI: 1.802-3.347, P=0.003), postoperative GCS score 3-5 ( OR=2.874, 95% CI: 2.265-3.449, P<0.001), postoperative hypoxemia ( OR=2.251, 95% CI: 1.673-2.842, P=0.010) and postoperative chronic hydrocephalus ( OR=1.642, 95% CI: 1.214-2.021, P=0.022) were risk factors for postoperative brain dysfunction, while ventilator-assisted ventilation ( OR=0.656, 95% CI: 0.132-0.828, P=0.038) was protective factors. The internal verification of the line chart model by Bootstrap resampling method shows that the model has high differentiation, accuracy and validity. Conclusion:The application of 3D printing-assisted localization in hematoma puncture and drainage can improve the puncture condition and the hematoma clearance rate and clinical effect of patients with hypertensive intracerebral hemorrhage. Advanced age, preoperative cerebral hernia and bleeding volume are related to postoperative brain dysfunction. Clinical attention should be paid to patients with risk indicators of postoperative brain dysfunction.

The liver has a complex cellular composition and a remarkable regenerative capacity. The primary cell types in the liver are two parenchymal cell populations, hepatocytes and cholangiocytes, that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells, endothelia and various hemopoietic cell populations. The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates, the extracellular matrix, working synergistically with soluble paracrine and systemic signals. In recent years, with the rapid development of genetic sequencing technologies, research on the liver's cellular composition and its regulatory mechanisms during various conditions has been extensively explored. Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases, offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation. This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair. Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.
Humans ; Liver/surgery* ; Hepatocytes/transplantation* ; Stem Cells/metabolism* ; Liver Diseases/surgery*

Neoadjuvant therapy, especially neoadjuvant chemoradiotherapy, has become the standard preoperative treatment for locally advanced resectable esophageal cancer, whereas the recurrence and distant metastasis rates after surgery remain high. In recent years, programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors have been widely adopted in immunotherapy for cancer. Whether PD-1/PD-L1 immune checkpoint inhibitors combined with neoadjuvant chemotherapy / neoadjuvant chemoradiotherapy could further improve clinical efficacy, increase the complete surgical resection rate and safety are current research hotspots. In this article, neoadjuvant immunotherapy combined with chemotherapy / radiochemotherapy for esophageal cancer was reviewed.

Objective:To compare the efficacy and safety of high- and standard-dose radiotherapy (HD-RT vs. SD-RT) during definitive concurrent chemoradiotherapy (dCCRT) for esophageal cancer (EC), aiming to assess the advantages and disadvantages of these two radiotherapy doses when using modern radiotherapy techniques. Methods:Literature review was conducted from PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang database, and abstracts of the American Society of Radiation Oncology (ASTRO) and the European Society of Radiotherapy and Oncology (ESTRO). Randomized controlled trials (RCT) comparing high-dose radiotherapy (HD-RT: ≥59.4 Gy,1.8 Gy per time) with standard-dose radiotherapy (SD-RT: 50 Gy, 2 Gy per time, or 50.4 Gy, 1.8 Gy per time) during dCCRT for EC were included. The retrieval time was from the establishment of the database to January 1, 2023. The meta-analysis was performed using Stata 16.0 software.Results:A total of 1 158 patients from 5 RCT that meet the inclusion criteria were finally included. In 4 RCT, subgroup analysis of 940 patients using modern radiotherapy techniques were performed. Patients in the HD-RT and SD-RT groups had similar 1-, 2-, and 3-year overall survival (OS)( RR=1.03, 95% CI=0.86-1.22, P=0.757; RR=1.05, 95% CI=0.94-1.17, P=0.433; RR=1.05, 95% CI=0.96-1.14, P=0.314; respectively) and 2- and 3-year locoregional progression-free survival (LRPFS) ( RR=0.94, 95% CI=0.82-1.08, P=0.390; RR=0.96, 95% CI=0.86-1.09, P=0.560; respectively). Patients in the HD-RT group had a higher incidence of grade ≥ 3 treatment-related adverse reactions rates ( OR=1.35, 95% CI=1.03-1.77, P=0.029) and treatment-related death rates ( OR=1.66, 95% CI=0.97-2.83, P=0.062) compared with their counterparts in the SD-RT group. In the subgroup analysis using modern radiotherapy techniques, HD-RT did not improve LRPFS compared to SD-RT, but increased the incidence of adverse reactions, and yielded no OS benefit. Conclusions:Whether modern precision radiation therapy is employed or not, SD-RT yields similar LRPFS and OS, and lower grade ≥ 3 treatment-related adverse reactions rates compared with HD-RT. Therefore, standard-dose (50 Gy, 2 Gy per time, or 50.4 Gy, 1.8 Gy per time) should be considered as the recommended dose in dCCRT for EC. Further RCT are needed to verify our conclusions.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V₂₀) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V₃₀) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients′age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients′ age, tumor diameter and tumor volume may impact patients′ prognosis.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.