Objective:To explore the effectiveness and safety of different anticoagulation strategies during continuous blood purification (CBP) treatment,providing a reference for anticoagulation strategies in critically ill children undergoing CBP.Methods:A retrospective study was conducted,including children admitted to the PICU of Children's Hospital of Fudan University from January 2019 to December 2024.According to the anticoagulation methods used during CBP treatment,patients were divided into the sodium citrate group and the heparin group.CBP was performed using continuous venovenous hemofiltration or continuous venovenous hemodialysis filtration mode,with a blood flow rate of 3-5 mL/(kg·min),replacement fluid rate of 30-50 mL/(kg·h),and dialysis fluid rate of 20-30 mL/(kg·h).The filter lifespan,28-day all-cause mortality,total length of hospital stay,PICU stay duration,adverse events,and associated costs were compared between the two groups.Results:A total of 221 children were included (105 in the sodium citrate group and 116 in the heparin group),with a cumulative use of 666 filters (284 in the sodium citrate group and 382 in the heparin group).(1) There were no statistically significant differences in general data,including age,sex ratio,underlying diseases,the ratio and duration of invasive mechanical ventilation,vasopressor scores at baseline,and indications for CBP between the two groups (all P>0.05).(2) The filter lifespan was 20(14,32) hours for the sodium citrate group and 21(13,35) hours for the heparin group,with no statistically significant difference between the two groups ( P>0.05); the proportion of accidental downstroke was 2.8% and 6.5%,respectively,with a statistically significant difference ( P=0.029); among the 221 children,86 died,with 38 deaths (35.2%) in the sodium citrate group and 49 deaths (38.9%) in the heparin group,showing no statistically significant difference.(3) The sodium citrate group had a higher incidence of metabolic alkalosis,hypocalcemia,and sodium citrate accumulation (44.4% vs. 1.6%,32.7% vs 9.4%,7.7% vs 0,all P<0.01); the heparin group had a greater proportion of bleeding (6.0% vs. 2.9%) and was more likely to develop heparin-induced thrombocytopenia (10.2% vs. 0, P<0.01).(4) The total hospitalization costs for the sodium citrate group were significantly higher than for the heparin group (200 327 yuan vs. 152 077 yuan, P=0.05); costs related to the use of anticoagulants and monitoring indicators during CBP treatment were also higher in the sodium citrate group (2 479 yuan vs. 682 yuan, P<0.01). Conclusions:Sodium citrate is a safe and effective anticoagulation method for critically ill children undergoing CBP,which can reduce the risk of filter clotting compared to systemic heparin anticoagulation.

As the pace of life accelerates, the incidence of grey hair increases significantly along with stress. However, the exact mechanism of hair graying remains unclear. Hair graying is not only a prominent marker of human aging but also closely associated with various serious systemic diseases, such as coronary heart disease and hypertension. Therefore, we review the mechanism of stress-induced hair graying as follow by searching the key words stress and grey hair. (1)Acute and chronic stressors promote the sympathetic nerve to release neurotransmitters(norepinephrine and P substance), which causes the exhaustion of melanocyte stem cells and hair greying. (2)Stress directly or indirectly promotes melanocyte apoptosis by inducing oxidative stress.(3)Stress disrupts melanogenesis by inducing the product of inflammatory factors and immune response to kill melanocytes, and regulating intracellular signaling. Our review is expected to provide a theoretical reference for the prevention and treatment of gray hair.

As the pace of life accelerates, the incidence of grey hair increases significantly along with stress. However, the exact mechanism of hair graying remains unclear. Hair graying is not only a prominent marker of human aging but also closely associated with various serious systemic diseases, such as coronary heart disease and hypertension. Therefore, we review the mechanism of stress-induced hair graying as follow by searching the key words stress and grey hair. (1)Acute and chronic stressors promote the sympathetic nerve to release neurotransmitters(norepinephrine and P substance), which causes the exhaustion of melanocyte stem cells and hair greying. (2)Stress directly or indirectly promotes melanocyte apoptosis by inducing oxidative stress.(3)Stress disrupts melanogenesis by inducing the product of inflammatory factors and immune response to kill melanocytes, and regulating intracellular signaling. Our review is expected to provide a theoretical reference for the prevention and treatment of gray hair.

Objective:To explore the effectiveness and safety of different anticoagulation strategies during continuous blood purification (CBP) treatment,providing a reference for anticoagulation strategies in critically ill children undergoing CBP.Methods:A retrospective study was conducted,including children admitted to the PICU of Children's Hospital of Fudan University from January 2019 to December 2024.According to the anticoagulation methods used during CBP treatment,patients were divided into the sodium citrate group and the heparin group.CBP was performed using continuous venovenous hemofiltration or continuous venovenous hemodialysis filtration mode,with a blood flow rate of 3-5 mL/(kg·min),replacement fluid rate of 30-50 mL/(kg·h),and dialysis fluid rate of 20-30 mL/(kg·h).The filter lifespan,28-day all-cause mortality,total length of hospital stay,PICU stay duration,adverse events,and associated costs were compared between the two groups.Results:A total of 221 children were included (105 in the sodium citrate group and 116 in the heparin group),with a cumulative use of 666 filters (284 in the sodium citrate group and 382 in the heparin group).(1) There were no statistically significant differences in general data,including age,sex ratio,underlying diseases,the ratio and duration of invasive mechanical ventilation,vasopressor scores at baseline,and indications for CBP between the two groups (all P>0.05).(2) The filter lifespan was 20(14,32) hours for the sodium citrate group and 21(13,35) hours for the heparin group,with no statistically significant difference between the two groups ( P>0.05); the proportion of accidental downstroke was 2.8% and 6.5%,respectively,with a statistically significant difference ( P=0.029); among the 221 children,86 died,with 38 deaths (35.2%) in the sodium citrate group and 49 deaths (38.9%) in the heparin group,showing no statistically significant difference.(3) The sodium citrate group had a higher incidence of metabolic alkalosis,hypocalcemia,and sodium citrate accumulation (44.4% vs. 1.6%,32.7% vs 9.4%,7.7% vs 0,all P<0.01); the heparin group had a greater proportion of bleeding (6.0% vs. 2.9%) and was more likely to develop heparin-induced thrombocytopenia (10.2% vs. 0, P<0.01).(4) The total hospitalization costs for the sodium citrate group were significantly higher than for the heparin group (200 327 yuan vs. 152 077 yuan, P=0.05); costs related to the use of anticoagulants and monitoring indicators during CBP treatment were also higher in the sodium citrate group (2 479 yuan vs. 682 yuan, P<0.01). Conclusions:Sodium citrate is a safe and effective anticoagulation method for critically ill children undergoing CBP,which can reduce the risk of filter clotting compared to systemic heparin anticoagulation.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To analyze the plasma levels of soluble immune checkpoint molecules in patients with primary liver cancer and their prognostic significance.Methods:The levels of sCD28, sCD80, sCD137, sCD27, sGITR, sTIM3, sCTLA4, sHVEM, IDO, sLAG3, sBTLA, sPD1, sPDL1 and sPDL2 in plasma samples of 58 patients with primary liver cancer and 30 healthy controls were detected by liquid chip technology and compared between different groups. The relationship between the plasma levels of soluble immune checkpoint molecules and tumor recurrence was analyzed.Results:The levels of sCD28 and sCD80 were higher in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0/A and B than in healthy controls and patients in BCLC-C stage ( P<0.05). However, the levels of sCD27 and sHVEM in BCLC-C patients were significantly lower than those in BCLC-0/A and BCLC-B patients, and even lower than healthy control group. The levels of sCD137, IDO and sPD1 in BCLC-0/A and BCLC-B patients were higher than those in healthy controls. The levels of sPDL1 and sPDL2 in different BCLC stages were all higher than those in healthy controls, and maintained at high level in the three stages, but there was no significant difference between different stages. After 24 months of interventional treatment, the preoperative sCD28 level was lower in patients with recurrent tumor recurrence than in patients without recurrence ( t=2.843, P=0.007). The optimal cut-off value of sCD28 based on the receiver operating characteristic (ROC) curve for predicting tumor recurrence was 101.42 pg/ml and the area under the ROC curve was 0.771 (95%CI: 0.611-0.931) with a sensitivity of 0.889 and a specificity of 0.666. The cumulative recurrence rate in patients with high sCD28 level (≥101.41 pg/ml) was 57.9% at 24 months after surgery, which was lower than the rate (95.5%) in patients with low sCD28 level (<101.41 pg/ml). The difference in the cumulative recurrence rate between the two groups was statistically significant (χ 2=15.777, P=0.000). Conclusions:The expression patterns of soluble immune checkpoint molecules varied in patients at different stages of primary liver cancer, suggesting that there were differences in their immune status and sCD28 could be used as a prognostic marker for postoperative recurrence of liver cancer.

Objective:To evaluate the effect of definitive radiotherapy with different doses on overall survival (OS) and identify the prognostic factors of patients with non-metastatic esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of 2 344 ESCC patients treated with definitive radiotherapy (RT) alone or chemoradiotherapy from 2002 to 2016 in 10 hospitals were collected and analyzed retrospectively. After the propensity score matching (PSM)(1 to 2 ratio), all patients were divided into the low-dose group (equivalent dose in 2 Gy fractions, EQD 2Gy<60 Gy; n=303) and high-dose group (EQD 2Gy≥60 Gy; n=606) based on the dose of radiation. Survival analysis was conducted by Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox′s regression model. Results:The median follow-up time was 59.6 months. After the PSM, the 1-, 3- and 5-year overall survival (OS) rate was 66.5%, 34.7%, 27.2% in the low-dose group, 72.9%, 41.7% and 34.7% in the high-dose group, respectively ( P=0.018). The 1-, 3-and 5-year progression-free survival rate was 52.2%, 27.2%, 23.1% in the low-dose group, 58.3%, 38.1% and 33.9% in the high-dose group, respectively ( P=0.001). The outcomes of univariate analysis indicated that cervical/upper esophagus location, early (stage Ⅱ) AJCC clinical stage, node negative status, tumor length ≤5 cm, receiving intensity-modulated radiation therapy (IMRT), receiving concurrent chemotherapy and EQD 2Gy≥60 Gy were closely associated with better OS (all P<0.05). Multivariable analysis demonstrated that tumor location, regional lymph node metastasis, concurrent chemotherapy and EQD 2Gy were the independent prognostic factors for OS (all P<0.05). Conclusion:Three-dimensional conformal or IMRT with EQD 2Gy≥60 Gy yields favorable survival outcomes for patients with locally advanced ESCC.

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.

Objective To investigate the expression of apolipoprotein (Apo) F in hepatocellular carcinoma (HCC) and its application value in the prognosis of patients with HCC. Methods 50 HCC samples were procured from patients undergoing surgical resection in the Third Affiliated Hospital of Sun Yat-sen University between September 2015 and September 2016, and all the samples were confirmed by postoperative pathological examination. The informed consents of all patients were obtained and the local ethical committee approval was received. There were 37 males and 13 females, aged from 31-67 with a median age of 53 years old. The expression of ApoF mRNA in HCC tissues was detected by RT-PCR. The expression profile was analyzed by using data from the Gene Expression Omnibus (GEO). The expression of ApoF between two groups were compared by t test. Correlation analysis of clinical related parameter was conducted by Chi-square test, and survival prognosis was analyzed by Kaplan-Meier test and Log rank test. Results The average relative expression of ApoF mRNA in HCC tissues was 0.15±0.07, significantly lower than 0.55±0.09 in the adjacent tissues (t=-6.26, P<0.05). GEO online analysis showed that expression of ApoF was significantly correlated with the status of liver cirrhosis, and most HCC patients with liver cirrhosis presented low expression of ApoF (χ2=4.626, P<0.05). The 5-year disease-free survival was respectively 55.9% and 32.0% in ApoF high expression group and low expression group, where significant difference was observed (χ2=3.939, P<0.05). Conclusions Low expression of ApoF exists in HCC tissues, and it is related to the liver cirrhosis status of patients. Patients with low ApoF expression present poorer prognosis. ApoF plays a role in inhibiting the cancer.

Objective:This study aims at exploring the impact of the health resources allocation on healthcare seeking behavior of inpatients with different income in China. Methods:Data at individual level were collected from China National Health Service Surveys conducted in 2008 and 2013 , interlinked with the data of health resources in county level. Multilevel zero-inflated negative binomial regression and multilevel multinomial logit model were respec-tively used to examine the impact of the health resources allocation on inpatient visits and the influence of the choice of healthcare providers by inpatients. Results: The results show that the increase of the number of beds in primary health centers ( PHCs) and physicians in county hospitals increased inpatient visits within counties. The investments in health resources in PHCs had greater impact on improving the likelihood of inpatient visits within counties for the low-income populations than that for the high-income populations. Conclusion: Investments in health resources in PHCs are vital to improve the healthcare seeking behaviors of the low-income populations in China.