Objective:To explore the application process, efficacy and safety of MR-guided radiotherapy based on MR-linac in esophageal cancer.Methods:The clinical data of patients with esophageal cancer treated with MR-linac at Shandong Cancer Hospital and Institute from September 2021 to July 2022 were retrospectively analyzed, to investigate the treatment process of esophageal cancer with MR-linac, and to analyze the efficacy and safety of patients. All patients received MR-guided radiotherapy, underwent CT and MR localization, target area delineation, and design of the Monaco treatment planning system plan. Adaptation-to-position adjustment was conducted during the pre-treatment evaluation. The median number of fractions was 25, the median single dose of planning target volume was 1.8 Gy, and the median total dose was 50.2 Gy. Median follow-up was 16 months.Results:Among the 12 patients in the whole group, there were 1 case of cervical esophageal cancer, 3 cases of upper thoracic esophageal cancer, 4 cases of middle thoracic esophageal cancer and 4 cases of lower thoracic esophageal cancer, including 3 cases of neoadjuvant radiotherapy and 9 cases of radical radiotherapy. All patients had a smooth treatment process. The median treatment time was 33 min, and the patients had good compliance. For patients with radical radiotherapy, one month after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 9; six months after radiotherapy, the number of objective remission cases was 3, and the number of disease-control cases was 6. All patients treated with neoadjuvant radiotherapy underwent surgery within 2 months, and one patient achieved pathological complete remission. The most common acute adverse reactions were radiation esophagitis (7 cases) and leukopenia in bone marrow suppression (8 cases), with late-stage adverse reactions being radiation pneumonia (1 case). The adverse reactions to radiotherapy were slight, and no grade 4 or above adverse reactions were observed.Conclusion:The clinical treatment process for esophageal cancer under MR-guided radiotherapy based on MR-linac is feasible, with good curative effects and mild adverse reactions.

Immunotherapy has entered the clinical treatment for various tumors, among which the blockade therapy of PD-1/PD-L1 immune checkpoint is currently the most important tumor immunotherapy method. At present, immunohistochemical method are used in clinical practice to detect PD-L1 expression in tumor patients and screen for indications. However, this method is constrained by factors such as heterogeneity, dynamic changes in PD-L1 expression, and limited sample collection. PD-(L)1 PET imaging utilizes radiolabeled molecules to non-invasively assess PD-(L)1 expression in space and time, and complementary use with IHC has theoretically incomparable advantages. This article reviews the latest progress in the PD-(L)1 probe molecular imaging principles, clinical research and existing problems.

Objective:To investigate the association between sleep status and the risk for coronary heart disease in adults in Suzhou.Methods:Using the baseline and follow up information of 53 269 local residents aged 30-79 years in China Kadoorie Biobank conducted in Wuzhong District, Suzhou, 51 929 subjects were included in this study after excluding those reporting coronary heart disease, stroke and cancer at the baseline survey. A Cox proportional hazards regression model was used to analyze the association of healthy sleep score (0-3 points) and sleep factors (snoring, insomnia, long sleep duration and nap) with the risk for coronary heart disease.Results:The median follow-up time was 11.12 years, and 1 304 individuals were diagnosed with coronary heart disease during the follow-up. After adjusting for potential confounders, occasional snoring ( HR=1.20, 95% CI: 1.04-1.38), usual snoring ( HR=1.17, 95% CI: 1.02-1.33), insomnia disorder ( HR=1.41, 95% CI: 1.12-1.78), daytime dysfunction ( HR=1.56, 95% CI: 1.20-2.03) and perennial nap ( HR=1.37, 95% CI: 1.19-1.59) were associated with increased risk of coronary heart disease. Compared with those with sleep score of 0 - 1 (low sleep quality), the people with sleep score of 3 had reduced risk of coronary heart disease by 26% ( HR=0.74, 95% CI: 0.63-0.87). Stratified analysis showed that the association of healthy sleep score 3 with risk of coronary heart disease was stronger in low physically active individuals (interaction P<0.05). Conclusions:Snoring, insomnia disorders, daytime dysfunction, and perennial napping were all associated with increased risk for coronary heart disease, and keep healthy sleep mode might reduce the risk for coronary heart disease in adults.

The important role of TDP-43 proteinopathy in Alzheimer's disease (AD) has been gradually revealed. High proportion of AD patients have TDP-43 proteinopathy on their postmortem diagnosis. Patients with TDP-43 proteinopathy show more sever hippocampal atrophy and cognitive dysfunction, suggesting that TDP-43 proteinopathy can serve as an important target in AD diagnosis and treatment. Evaluation of TDP-43 proteinopathy in vivo would hold great promise in AD diagnosis, drug development and treatment. In this review, we describe the pathological characteristics of TDP-43 proteinopathy in AD, and summarize the recent progress of TDP-43 proteinopathy in the diagnosis and treatment of AD.

OBJECTIVE: To observe the expression level of cytokines in patients with sepsis and its effect on prognosis. METHODS: The clinical data of sepsis patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were analyzed retrospectively, including gender, age, and acute physiology and chronic health evaluation II (APACHE II), blood routine, procalcitonin (PCT), C-reactive protein (CRP), and cytokines levels [interleukins (IL-2, IL-4, IL-6, IL-10, IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)] within 24 hours of admission to ICU. The 28-day prognosis of the patients was followed up. The patients were divided into survival group and death group according to the prognosis. The clinical data between the two groups of sepsis patients with different prognosis were compared. Binary Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of patients with sepsis, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each risk factor for the prognosis of patients with sepsis. RESULTS: (1) A total of 227 patients with sepsis were enrolled, including 168 patients in the survival group (survival rate 74.0%) and 59 patients in the death group (mortality 26.0%). There were no significant differences in age (years old: 55.97±2.13 vs. 54.67±1.11) and gender (male: 71.2% vs. 57.1%) between the death group and the survival group (both P > 0.05), indicating that the baseline data of the two groups were comparable. (2) The APACHE II (19.37±0.99 vs. 14.88±0.61, P < 0.001) and PCT (μg/L: 12.39±2.94 vs. 4.14±0.90, P < 0.001) in the death group were significantly higher than those in the survival group, while the platelet count [PLT (×10⁹/L): 144.75±12.50 vs. 215.99±11.26, P = 0.001] and thrombocytocrit [(0.14±0.01)% vs. (0.19±0.01)%, P = 0.001] were significantly lower than those in the survival group. (3) The level of IL-6 in the death group was significantly higher than that in the survival group (ng/L: 577.66±143.16 vs. 99.74±33.84, P < 0.001). There were no statistically significant differences in other cytokines, IL-2, IL-4, IL-10, TNF-α, IFN-γ and IL-17 between the death group and the survival group [IL-2 (ng/L): 2.44±0.38 vs. 2.63±0.27, P = 0.708; IL-4 (ng/L): 3.26±0.67 vs. 3.18±0.34, P = 0.913; IL-10 (ng/L): 33.22±5.13 vs. 39.43±2.85, P = 0.262; TNF-α (ng/L): 59.33±19.21 vs. 48.79±29.87, P = 0.839; IFN-γ (ng/L): 6.69±5.18 vs. 1.81±0.16, P = 0.100; IL-17 (ng/L): 2.05±0.29 vs. 2.58±0.33, P = 0.369]. (4) Binary Logistic regression analysis showed that APACHE II and IL-6 were independent risk factors affecting the prognosis of patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.050 (1.008-1.093) and 1.001 (1.000-1.002), P values were 0.019 and 0.026, respectively]. (5) ROC curve analysis showed that APACHE II and IL-6 had certain predictive value for the prognosis of patients with sepsis, the area under the ROC curve (AUC) was 0.754 (95%CI was 0.681-0.827) and 0.592 (95%CI was 0.511-0.673), P values were < 0.001 and 0.035, respectively. When the optimal cut-off value of APACHE II was 16.50 score, the sensitivity was 72.6% and the specificity was 69.9%. When the optimal cut-off value of IL-6 was 27.87 ng/L, the sensitivity was 67.2% and the specificity was 52.8%. CONCLUSIONS APACHE II score and IL-6 level have certain predictive value for the prognosis of patients with sepsis, the higher APACHE II score and IL-6 level, the greater the probability of death in patients with sepsis.
Humans ; Male ; Interleukin-10 ; Interleukin-17 ; Cytokines ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Retrospective Studies ; Interleukin-2 ; Interleukin-4 ; ROC Curve ; Sepsis/diagnosis* ; Prognosis ; Procalcitonin ; Interferon-gamma ; Intensive Care Units

Objective:To investigate the predictive value of the maximum aggregation rate (MAR) of platelet for septic shock and septic shock with disseminated intravascular coagulation (DIC).Methods:A retrospective case-control study enrolled patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022. The basic data, dynamic platelet aggregation rate, blood routine, inflammation indicators, sequential organ failure assessment (SOFA) and other clinical indicators within 24 hours after admission were collected. Septic patients were divided into the shock group and the non-shock group according to the presence of septic shock; then refer to the International Society on Thrombosis and Hemostasis (ISTH) standard, patients with septic shock were divided into the shock DIC group and the shock non-DIC group according to the presence of dominant DIC. Compared the differences in platelet aggregation function between these groups, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the MAR for septic shock and septic shock with DIC. Spearman correlation analysis was used to analyze the correlation of MAR with inflammation indicators and the severity of illness in patients with sepsis.Results:A total of 153 sepsis patients were included and 61 with septic shock (including 17 with dominant DIC and 44 without dominant DIC). Compared with the non-shock group, the level of procalcitonin (PCT), C-reactive protein (CRP), and SOFA score were significantly higher in the shock group [PCT (mg/L): 6.90 (2.50, 23.50) vs. 0.87 (0.26, 5.75), CRP (mg/L): 156.48 (67.11, 230.84) vs. 90.39 (46.43, 182.76), SOFA score: 11.00 (8.00, 14.00) vs. 5.00 (3.00, 8.00), all P < 0.05]. The platelet count (PLT) and the MAR induced by adenosine diphosphate (ADP), adrenaline (A), collagen (COL), and arachidonic acid (AA; ADP-MAR, A-MAR, COL-MAR, AA-MAR) in the shock group were significantly decreased [PLT (×10 9/L): 101.00 (49.00, 163.50) vs. 175.50 (108.25, 254.50), ADP-MAR: 28.50% (22.00%, 38.05%) vs. 45.90% (33.98%, 60.28%), A-MAR: 38.90% (30.00%, 55.40%) vs. 65.15% (54.38%, 72.53%), COL-MAR: 27.90% (20.85%, 36.55%) vs. 42.95% (33.73%, 54.08%), AA-MAR: 24.70% (16.40%, 34.20%) vs. 46.55% (28.33%, 59.20%), all P < 0.05]. Subgroup analysis revealed that, compared with the shock non-DIC group, the SOFA scores were significantly higher in patients in the shock DIC group (13.29±5.23 vs. 10.39±3.58, P < 0.05), the PLT and COL-MAR in the shock DIC group were significantly reduced [PLT (×10 9/L): 36.00 (22.00, 67.50) vs. 115.50 (84.25, 203.75), COL-MAR: 21.50% (17.85%, 32.60%) vs. 30.95% (22.98%, 38.53%), all P < 0.05]. ROC curve analysis showed that A-MAR had a higher predictive value for septic shock, and the area under the ROC curve (AUC) was 0.814 [95% confidence interval (95% CI) was 0.742-0.886, P = 0.000]. When the optimal cut-off value was 51.35%, the sensitivity was 68.9%, the specificity was 82.6%, the positive predictive value was 0.724 and the negative predictive value was 0.800. COL-MAR had some predictive value for septic shock with DIC, and the AUC was 0.668 (95% CI was 0.513-0.823, P = 0.044). When the optimal cut-off value was 21.90%, the sensitivity was 52.9%, the specificity was 79.5%, the positive predictive value was 0.500, and the negative predictive value was 0.813. Spearman correlation analysis showed that the MAR induced by each inducer was negatively correlated with inflammatory indicators and SOFA scores in sepsis patients, with A-MAR showing the strongest correlation with SOFA score ( r = -0.327, P = 0.000). Conclusions:MAR, an indicator of platelet aggregation function, shows predictive value for septic shock and septic shock with DIC, and it could be used to for evaluating the severity of patients with sepsis. In addition, tt alsocan be used as a monitoring index to predict the changes of sepsis patients and to guide the treatment.

OBJECTIVE: To explore the relevant clinical test indicators that affect the prognosis of patients with acute fatty liver of pregnancy (AFLP), and to provide a basis for early diagnosis and correct selection of treatment methods. METHODS: A retrospective analysis was conducted. Clinical data of AFLP patients in the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2010 to May 2021 were collected. According to the 28-day prognosis, the patients were divided into death group and survival group. The clinical data, laboratory examination indicators, and prognosis of the two groups were compared, and further binary Logistic regression analysis was used to analyze the risk factors affecting the prognosis of patients. At the same time, the values of related indicators at each time point (24, 48, 72 hours) after the start of treatment were recorded. The receiver operator characteristic curve (ROC curve) of prothrombin time (PT) and international normalized ratio (INR) for evaluating the prognosis of patients at each time point was drawn, and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of relevant indicators at each time point for the prognosis of AFLP patients. RESULTS: A total of 64 AFLP patients were selected. The patients developed the AFLP during pregnancy (34.5±6.8) weeks, with 14 deaths (mortality of 21.9%) and 50 survivors (survival rate of 78.1%). There was no statistically significant difference in general clinical data between the two groups of patients, including age, time from onset to visit, time from visit to cessation of pregnancy, acute physiology and chronic health evaluations II (APACHE II), hospitalization time in ICU, and total hospitalization cost. However, the proportion of male fetuses and stillbirths in the death group was higher than that in the survival group. The laboratory examination indicators including the white blood cell count (WBC), alanine transaminase (ALT), serum creatinine (SCr), PT extension, INR elevation, and hyperammonia in the death group were significantly higher than those in the survival group (all P < 0.05). Through Logistic regression analysis of the above indicators showed that PT > 14 s and INR > 1.5 were risk factors affecting the prognosis of AFLP patients [PT > 14 s: odds ratio (OR) = 1.215, 95% confidence interval (95%CI) was 1.076-1.371, INR > 1.5: OR = 0.719, 95%CI was 0.624-0.829, both P < 0.01]. ROC curve analysis showed that both PT and INR at ICU admission and 24, 48, and 72 hours of treatment can evaluate the prognosis of AFLP patients [AUC and 95%CI of PT were 0.772 (0.599-0.945), 0.763 (0.608-0.918), 0.879 (0.795-0.963), and 0.957 (0.904-1.000), respectively; AUC and 95%CI of INR were 0.808 (0.650-0.966), 0.730 (0.564-0.896), 0.854 (0.761-0.947), and 0.952 (0.896-1.000), respectively; all P < 0.05], the AUC of PT and INR after 72 hours of treatment was the highest, with higher sensitivity (93.5%, 91.8%) and specificity (90.9%, 90.9%). CONCLUSIONS AFLP often occurs in the middle and late stages of pregnancy, and the initial symptoms are mainly gastrointestinal symptoms. Once discovered, pregnancy should be terminated immediately. PT and INR are good indicators for evaluating AFLP patient efficacy and prognosis, and PT and INR are the best prognostic indicators after 72 hours of treatment.
Humans ; Male ; Prognosis ; ROC Curve ; Retrospective Studies ; Intensive Care Units ; Sepsis/diagnosis*

OBJECTIVE: To explore the characteristics of changes in peripheral blood lymphocyte subsets in patients with sepsis in intensive care unit (ICU) and analyze their predictive value for prognosis. METHODS: The clinical data of sepsis patients admitted to the surgical intensive care unit (SICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were analyzed retrospectively. The patients met the diagnostic criteria of Sepsis-3 and were ≥ 18 years old. Peripheral venous blood samples were collected from all patients on the next morning after admission to SICU for routine blood test and peripheral blood lymphocyte subsets. According to the 28-day survival, the patients were divided into two groups, and the differences in immune indexes between the two groups were compared. Logistic regression analysis was used to analyze the risk factors of immune indexes that affect prognosis. RESULTS: (1) A total of 279 patients with sepsis were enrolled in the experiment, of which 198 patients survived at 28 days (28-day survival rate 71.0%), and 81 patients died (28-day mortality 29.0%). There were no significant differences in age (years old: 57.81±1.71 vs. 54.99±1.05) and gender (male: 60.5% vs. 63.6%) between the death group and the survival group (both P > 0.05), and the baseline data was comparable.(2) Acute physiology and chronic health evalution II (APACHE II: 22.06±0.08 vs. 14.08±0.52, P < 0.001), neutrophil percentage [NEU%: (88.90±1.09)% vs. (84.12±0.77)%, P = 0.001], procalcitonin [PCT (μg/L): 11.97±2.73 vs. 5.76±1.08, P = 0.011], platelet distribution width (fL: 16.81±0.10 vs. 16.57±0.06, P = 0.029) were higher than those in the survival group, while lymphocyte percentage [LYM%: (6.98±0.78)% vs. (10.59±0.86)%, P = 0.012], lymphocyte count [LYM (×10⁹/L): 0.70±0.06 vs. 0.98±0.49, P = 0.002], and platelet count [PLT (×10⁹/L): 151.38±13.96 vs. 205.80±9.38, P = 0.002], and thrombocytocrit [(0.15±0.01)% vs. (0.19±0.07)%, P = 0.012] were lower than those in the survival group. (3) There was no statistically significant difference in the percentage of lymphocyte subsets between the death group and the survival group, but the absolute value of LYM (pieces/μL: 650.24±84.67 vs. 876.64±38.02, P = 0.005), CD3⁺ absolute value (pieces/μL: 445.30±57.33 vs. 606.84±29.25, P = 0.006), CD3⁺CD4⁺ absolute value (pieces/μL: 239.97±26.96 vs. 353.49±18.59, P = 0.001), CD19⁺ absolute value (pieces/μL: 111.10±18.66 vs. 150.30±10.15, P = 0.049) in the death group was lower than those in the survival group. Other lymphocyte subsets in the death group, such as CD3⁺CD8⁺ absolute value (pieces/μL: 172.40±24.34 vs. 211.22±11.95, P = 0.112), absolute value of natural killer cell [NK (pieces/μL): 101.26±18.15 vs. 114.72±7.64, P = 0.420], absolute value of natural killer T cell [NKT (pieces/μL): 33.22±5.13 vs. 39.43±2.85, P = 0.262], CD4^-CD8^- absolute value (pieces/μL: 41.07±11.07 vs. 48.84±3.31, P = 0.510), CD4⁺CD8⁺ absolute value (pieces/μL: 3.39±1.45 vs. 3.47±0.36, P = 0.943) were not significantly different from those in the survival group. (4)Logistic regression analysis showed that lymphocyte subsets were not selected as immune markers with statistical significance for the prognosis of sepsis. CONCLUSIONS The changes of immune indexes in sepsis patients are closely related to their prognosis. Early monitoring of the above indexes can accurately evaluate the condition and prognosis of sepsis patients.
Humans ; Male ; Adolescent ; Retrospective Studies ; ROC Curve ; Sepsis/diagnosis* ; Lymphocyte Count ; Lymphocyte Subsets ; Prognosis ; Killer Cells, Natural

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To discuss the feasibility of using online and offline combined multidisciplinary team (MDT) diagnosis-treatment mode in cancers diagnosis and treatment by comparing the comprehensive diagnosis and treatment plans formulated by online and offline MDT diagnosis-treatment mode.Methods:A total of 168 esophageal cancer patients collected from March 17, 2020 to May 17, 2020 were took as the research objects in Shandong Cancer Hospital and Institute, through whom the consistency of the comprehensive diagnosis and treatment plans formulated by online and offline MDT diagnosis-treatment mode was evaluated. The clinical characteristics of patients with changed comprehensive diagnosis and treatment plans, such as age, Karnofsky performance status (KPS) score, whether combined with basic diseases, whether received anti-tumor treatment before and tumor location were analyzed, so as to explore the mechanism to improve the efficiency on the basis of quality assurance.Results:The results showed that 86.3% (145/168) of the comprehensive diagnosis and treatment plans obtained by offline MDT diagnosis-treatment mode were consistent with online diagnosis-treatment MDT mode. Cases with inconsistent comprehensive diagnosis and treatment plans were characterized by elderly (> 69 years) ( χ2=4.250, P=0.039), KPS score≥80 ( χ2=15.520, P<0.001) and combined with underlying disease ( χ2=7.135, P=0.008). Through further analysis, the changed cases were also characterized as with inadequate auxiliary examination or complex in imaging. Conclusion:The online and offline combined MDT diagnosis-treatment mode is feasible. For the patients characterized of elderly (> 69 years old), KPS score ≥80, combined with underlying diseases, with incomplete auxiliary examination or complex in imaging, the offline MDT diagnosis-treatment mode should be adopted or supplemented.