Impact of Different Diagnostic Measures on Drug Class Association with Dementia Progression Risk: A Longitudinal Prospective Cohort Study.

Background: The Clinical Dementia Rating Scale Sum of Boxes (CDRSOB) score is known to be highly indicative of cognitive-functional status and is regularly employed for clinical and research purposes. Objective: Our aim is to determine whether CDRSOB is consistent with clinical diagnosis in evaluating drug class associations with risk of progression to mild cognitive impairment (MCI) and dementia. Methods: We employed weighted Cox regression analysis on longitudinal NACC data, to identify drug classes associated with disease progression risk, using clinical diagnosis and CDRSOB as the outcome. Results: Aspirin (antiplatelet/NSAID), angiotensin II inhibitors (antihypertensive), and Parkinson's disease medications were significantly associated with reduced risk of progression to MCI/dementia and Alzheimer's disease medications were associated with increased MCI-to-Dementia progression risk with both clinical diagnosis and CDRSOB as the outcome. However, certain drug classes/subcategories, like anxiolytics, antiadrenergics, calcium (Ca2+) channel blockers, and diuretics (antihypertensives) were associated with reduced risk of disease progression, and SSRIs (antidepressant) were associated with increased progression risk only with CDRSOB. Additionally, metformin (antidiabetic medication) was associated with reduced MCI-to-Dementia progression risk only with clinical diagnosis as the outcome. Conclusions: Although the magnitude and direction of the effect were primarily similar for both diagnostic outcomes, we demonstrate that choice of diagnostic measure can influence the significance of risk/protection attributed to drug classes and consequently the conclusion of findings. A consensus must be reached within the research community with respect to the most accurate diagnostic outcome to identify risk and improve reproducibility.

Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.

Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.

Background: The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. Methods: From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Results: Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. Conclusions: AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

Development and validation of nomograms to predict survival and recurrence after hepatectomy for intermediate/advanced (BCLC stage B/C) hepatocellular carcinoma.

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

Long-term outcomes following hepatectomy in patients with lean non-alcoholic fatty liver disease-associated hepatocellular carcinoma versus overweight and obese counterparts: A multicenter analysis.

BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals. METHODS: A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m2), overweight (23.0-27.4 kg/m2) and obese (≥27.5 kg/m2) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups. RESULTS: Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06-2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17-2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC. CONCLUSIONS: Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence.

Efficacy analysis of blood inflammation and liver function indexes in ICP diagnosis and delivery mode prediction / 重庆医学

Objective To observe the changes of laboratory blood indexes in patients with intrahepatic cholestasis of pregnancy(ICP),and analyze the value of blood inflammation indexes and liver function indexes in the diagnosis of ICP and the prediction of delivery mode.Methods A total of 251 patients diagnosed with ICP in this hospital from January 2021 to December 2022 were selected as the ICP group,and another 200 healthy pregnant women were selected as the control group.The patients with ICP were further divided into the severe ICP group(n=47)and the mild ICP group(n=204),the vaginal delivery group(n=113)and the cesarean section group(n=138)according to the severity of ICP and delivery mode.Mann-Whitney U test was used for comparison of parameters between groups,and Spearman method was used for correlation analy-sis.Receiver operating characteristic(ROC)curves were used to evaluate the efficacy of laboratory indicators in diagnosing ICP and predicting delivery mode.Results Neutrophil/lymphocyte ratio(NLR)[6.01(4.45,8.37)vs.3.36(4.12,3.51)]and aspartate transaminase(AST)level[20.00(16.00,33.00)U/L vs.15.00(13.00,18.00)U/L]in the ICP group were significantly higher than those in the control group(P＜0.05),and NLR in the severe ICP group was significantly higher than that in the mild ICP group[4.93(3.87,7.35)vs.4.14(3.12,5.17),P＜0.05].Correlation analysis showed that NLR was positively correlated with AST level(r=0.279,P＜0.001)and ICP severity(r=0.139,P=0.028)in patients with ICP.The area under ROC curve(AUC)of NLR combined with AST for ICP diagnosis was 0.882(95％CI:0.851-0.913).In ad-dition,cholinesterase(CHE)[6 020.00(5 499.50,6 703.50)U/L vs.5 341.50(4 651.75,6 259.25)U/L]and prealbumin(PA)[199.00(177.71,225.20)mg/Lvs.169.17(139.18,204.40)mg/L]levels in the va-ginal delivery group were significantly higher than those in the cesarean section group(P＜0.05),and the AUC of CHE combined with PA for predicting vaginal delivery in ICP patients was 0.727(95％CI:0.664-0.789).Conclusion NLR and AST have potential value in the diagnosis of ICP,and CHE and PA have poten-tial value in predicting delivery mode of ICP patients.

Current status and progress of proton and heavy ion radiotherapy for glioma in adults / 中华放射肿瘤学杂志

Glioma is the most common primary malignant brain tumor. Surgery combined with postoperative radiotherapy is the standard treatment, but the outcome is unsatisfactory. Currently, proton and carbon ion, the most advanced radiotherapy technology, offer substantial clinical advantages over the conventional photon therapy in multiple tumors. However, the effect of proton and carbon ion radiotherapy in glioma has not been clarified clearly. This article will elaborate on the basic research and clinical outcomes of proton and carbon ion radiotherapy for glioma.

A case report of β-ketothiolase deficiency / 中华实用儿科临床杂志

The clinical data of a child diagnosed with β-ketothiolase deficiency in Children′s Hospital of Chongqing Medical University in September 2018 were reviewed, and nutritional intervention and follow-up were carried out.The male child was 1 year and 4 months old, and he had clinical manifestations, including vomiting, diarrhea, mental depression and repeated metabolic acid poisoning.Gene detection: heterozygous variation of ACAT1 gene c. 401T>C (p.M134T) and c. 481T > C (p.Y161H). This study was mainly aimed at children with β-ketothiolase deficiency for nutritional treatment of individualized nutrition therapy, suggests that energy supply should be guaranteed and protein and fat intake should be limited in acute stage, and protein and fat intake should be increased gradually in remission stage, which can not only ensure growth and development, but also reduce the occurrence of metabolic crisis.

Modified Procedures for ALPPS Based on a Risk-Reduced Strategy: Paralleled Clinical Evaluation at Multiple Institutions

Purpose@#We compared the clinical outcomes of modified procedures for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) based on a risk-reduced strategy with those of classic ALPPS procedures in treating large liver carcinoma. @*Materials and Methods@#Short-term outcomes, increases in future liver remnant (FLR) and functional FLR (FFLR), and overall survival (OS) were compared between 45 consecutive patients treated with modified ALPPS procedures and 34 patients treated with classic ALPPS procedures. @*Results@#Clinical outcomes after the 1st-stage operation markedly improved with the modified procedures. Although the proportions of liver cirrhosis and hepatocellular carcinoma were higher in the modified group, the mortality and incidence of severe complications did not increase. FLR and FFLR hypertrophy at 1 week after the 1st-stage operation were similar in both groups; however, kinetic growth rates in the modified group were lower. OS rates were similar. @*Conclusion@#Modified ALPPS procedures could be safely applied to provide long-term survival for patients with liver cirrhosis without sufficient FLR.

Modified Procedures for ALPPS Based on a Risk-Reduced Strategy: Paralleled Clinical Evaluation at Multiple Institutions

Purpose@#We compared the clinical outcomes of modified procedures for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) based on a risk-reduced strategy with those of classic ALPPS procedures in treating large liver carcinoma. @*Materials and Methods@#Short-term outcomes, increases in future liver remnant (FLR) and functional FLR (FFLR), and overall survival (OS) were compared between 45 consecutive patients treated with modified ALPPS procedures and 34 patients treated with classic ALPPS procedures. @*Results@#Clinical outcomes after the 1st-stage operation markedly improved with the modified procedures. Although the proportions of liver cirrhosis and hepatocellular carcinoma were higher in the modified group, the mortality and incidence of severe complications did not increase. FLR and FFLR hypertrophy at 1 week after the 1st-stage operation were similar in both groups; however, kinetic growth rates in the modified group were lower. OS rates were similar. @*Conclusion@#Modified ALPPS procedures could be safely applied to provide long-term survival for patients with liver cirrhosis without sufficient FLR.

Advances in Research on Pharmacological Effect of Astragaloside Ⅳ on Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Astragalus membranaceus has the effect of tonifying Qi and solid surface， diuretic support poison， discharging pus and astringent sores to produce muscle. It is not only used for syndromes such as deficiency of lung and temper， deficiency of spleen and diarrhea， but also for stroke， chest obstruction and other diseases. Due to the complex chemical composition and diverse pharmacological effect of Astragalus membranaceus， and the main role in invigorating qi and activating blood circulation has not been clarified. Astragaloside Ⅳ is one of its main active ingredients. In recent years， more and more studies on Astragaloside Ⅳ have been conducted at home and abroad. It has been reported that it has the medicinal value of enhancing immune function， strengthening heart and lowerin blood glucose， diuresis， anti-aging and anti-fatigue， et al， and has extensive pharmacological activity. Among them， the role of cardiovascular and cerebrovascular diseases in particular has attracted increasing attention. Cardiovascular and cerebrovascular diseases are ischemic or hemorrhagic diseases occurring in the heart， brain and systemic tissues due to blood viscosity， atherosclerosis， hypertension， hyperlipidemia， etc.， including cardiovascular and cerebrovascular diseases. Such diseases are a serious threat to mankind and are the leading cause of death worldwide. At present， western medicine is the main treatment， with many adverse reactions and poor long-term prognosis. TCM believes that the imbalance of qi and blood is the basic pathogenesis of this kind of disease. Qi deficiency and blood stasis are more common.At present， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases in a number of studies， and achieved some results， but this review in recent years， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases play the pharmacological activity， in order to explore whether Astragaloside Ⅳ is the main role of astragalus qi to find a theoretical basis for material basis， but also for the innovation of traditional Chinese medicine drug research and development of theoretical basis and practical guidance.

Development and validation of a deep learning model to screen hypokalemia from electrocardiogram in emergency patients / 中华医学杂志(英文版)

BACKGROUND@#A deep learning model (DLM) that enables non-invasive hypokalemia screening from an electrocardiogram (ECG) may improve the detection of this life-threatening condition. This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients.@*METHODS@#We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University, Jiangxi, China, from September 2017 to October 2020. The DLM was trained using 12 ECG leads (lead I, II, III, aVR, aVL, aVF, and V1-6) to detect patients with serum potassium concentrations <3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University. The blood draw was completed within 10 min before and after the ECG examination, and there was no new or ongoing infusion during this period.@*RESULTS@#We used 6904 ECGs and 1726 ECGs as development and internal validation data sets, respectively. In addition, 1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets. Using 12 ECG leads (leads I, II, III, aVR, aVL, aVF, and V1-6), the area under the receiver operating characteristic curve (AUC) of the DLM was 0.80 (95% confidence interval [CI]: 0.77-0.82) for the internal validation data set. Using an optimal operating point yielded a sensitivity of 71.4% and a specificity of 77.1%. Using the same 12 ECG leads, the external validation data set resulted in an AUC for the DLM of 0.77 (95% CI: 0.75-0.79). Using an optimal operating point yielded a sensitivity of 70.0% and a specificity of 69.1%.@*CONCLUSIONS@#In this study, using 12 ECG leads, a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80. Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.

Primary results of proton radiotherapy for 26 meningioma patients / 中华放射医学与防护杂志

Objective:To investigate the safety and efficacy of proton beam radiation therapy (PBRT) in patients with World Health Organization (WHO) GradeⅠ/Ⅱ meningioma.Methods:Twenty-six patients with intracranial ( n=8, 30.8%) or skull-base ( n=18, 69.2%) meningioma treated with PBRT from May 2015 to October 2018 were analyzed retrospectively. The median age of the cohort was 42 years (range 15-79 years). Eight patients had WHO Grade Ⅰ meningioma, and 9 had WHO Grade Ⅱ meningioma, respectively. Nine patients had clinical (radiological) diagnosis without histology. Seven patients received post-surgical PBRT (2 patients underwent Simpson Ⅰ-Ⅲ resection, 5 patients underwent Simpson Ⅳ-Ⅴ resection); 10 patients were irradiated for local recurrence after initial surgical resection. Results:All patients completed planned PBRT without break, and the median dose was 54 Gray-Equivalent (GyE) (range 50.4-60 GyE, 1.8-2 GyE/daily fraction). With a median follow-up of 22.2 (range 1.6-36.4) months, the 2-year overall survival and progression-free survival rates were both 100%. Grade Ⅰ skin erythema and alopecia were observed in 22 patients and Grade Ⅰ mucositis was observed in 2 patients. No acute of late toxicities of Grade 2 or above was observed.Conclusions:PBRT appeared to be a favorable treatment option for intracranial and skull base meningioma. Treatment-induced adverse effects and early response to PBRT were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.

The preliminary result of proton and carbon ion therapy for recurrent chordoma and chondrosarcoma of skull base and cervical spine / 中华放射医学与防护杂志

Objective:To evaluate the short-term tumor control and toxicity of recurrent skull base and cervical spine chordoma and chondrosarcoma in patients treated with pencil beam scanning proton and heavy ion therapy.Methods:Between June 30 th, 2014 and July 30 th, 2018, a total of 45 skull base and cervical spine chordoma ( n=39) and chondrosarcoma ( n=6) patients (28 males and 17 females; mean age at initial presentation of 44 years, range, 14-76 years) were treated in our center for the course of radiotherapy. The median maximum tumor volume was 57 cm 3 (range, 6.6-231.7 cm 3). There were 31 post-operative recurrent patients and 14 post-operative and post-radiated recurrent patients. One patient received proton therapy, 21 patients received combined proton and carbon ion therapy, 23 patients received carbon ion therapy. Results:All patients completed the whole course of the treatment. The median follow-up time was 29 months (range: 8-57 months), the 2-year overall survival (OS), local control (LC), and progression-free survival (PFS) were 82.7%, 85.3%, and 73.8%, respectively. There were no other grade 3-4 acute or late radiation-induced toxicity except one grade 3 acute mucositis. The 2-year OS rates for patients after first-time radiation vs. re-irradiation were 96.2% and 50.3% ( χ2=16.969, P<0.05). Conclusions:The short-term outcomes of pencil beam scanning proton and heavy ion therapy for recurrent skull base and cervical spine chordoma and chondrosarcoma is favorable. Further study is needed for long-term efficacy and safety.

Preliminary study of intensity-modulated carbon ion reirradiation for locoregionally recurrent nasopharyngeal carcinoma after definitive IMRT——Clinical experience from Shanghai Proton Heavy Ion Hospital / 中华放射肿瘤学杂志

Objective To evaluate the short-term efficacy and toxicities of intensity-modulated carbon ion radiotherapy (IMCT) for patients with locoregionally recurrent nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT).Methods A total of 112 patients with locoregionally recurrent nasopharyngeal carcinoma undergoing salvaging IMCT between May 2015 and February 2018were enrolled in the study.All patients previously received one course of definitive X-ray IMRT.Among them,10 patients (9％) were diagnosed with stage Ⅰ,26 patients (23％) with stage Ⅱ,41 patients (37％) with stage Ⅲ and 35 patients (31％) with stage Ⅳnasopharyngeal carcinoma,respectively.The median age of the cohort was 48 years (range,17-70 years) old.The median dose to the gross tumor volume (GTV) was 60 GyE (range,50-69 GyE).Results With a median follow-up time of 20 months (range,5-45 months),20 patients died and 42 patients developed local recurrence.The 2-year overall survival (OS) and local progression-free survival (LPFS) rates were 85％ and 52％.Both univariate and multivariate analyses demonstrated that stage Ⅳ disease was associated with significantly worse OS.No predictors were found for LPFS.No acute toxicity of grade 3 or higher was observed during reirradiation.Severe (grade 3 or above) late toxicities included xerostomia (n =1),hearing impairment (n =2),temporal lobe injury (n =1) and mucosal necrosis (n =19).Conclusions IMCT is an efficacious and safe treatment for patients with locoregionally recurrent nasopharyngeal carcinoma with acceptable toxicity profile.Long-term follow-up is necessary to further evaluate the long-term efficacy and late toxicities.

Dosimetric study of particle radiotherapy for glioma patients / 中华放射肿瘤学杂志

Objective:To investigate the dosimetric difference between glioma patients treated by particle (proton+ carbon ion) and photon radiotherapy.Methods:Twelve previously-treated glioma patients were selected, and given with the same total dose of 60.00 Gy [RBE]. Two types of planning target volumes (PTVs) including PTV-ion and PTV-photon were expended from clinical target volumes according to range uncertainty and patient setup errors. Based on PTV-ion, proton plans with sequential carbon ion boost (particle plan) were created. Following the same prescription, two types of photon intensity-modulated radiotherapy (IMRT) plans were established to achieve similar target coverage and compare the dose of organs at risk.Results:Target coverages of three types of plans had no statistical difference (all P>0.05). The median integral dose of normal brain of all patients receiving particle plan was merely 44.90% of the minimum number from photon plans ( P<0.001). Compared with the minimum number from photon plans, particle radiotherapy decreased the mean dose of brain stem[(6.83±6.22) Gy[RBE] vs. (15.10±10.11) Gy[RBE], P=0.001)], the maximum dose of chiasm[(47.76±20.80) Gy[RBE] vs. (49.59±20.52) Gy[RBE], P=0.009)] and the mean dose of contralateral hippocampus (0.26±9.08) Gy[RBE] vs. (16.28±11.14) Gy[RBE], P=0.002), respectively. Conclusions:Particle radiotherapy can achieve similar target coverage while maintaining lower normal tissue doses to the photon radiotherapy. Photon planion can increase the doses to adjuvant normal tissues.

Effect of Astragali Radix Membranaceus in Promoting Blood Circulation and Its Modern Pharmacology Research / 中国实验方剂学杂志

Astragali Radix membranaceus is first recorded in Shennong Bencaojing, which has the effect in replenishing Qi and rising Yang, strengthening the body surface resistance, inducing diuresis to alleviate edema, and supporting for detoxication and tissue generation. As an essential medicine for invigorating Qi and invigorating the spleen, it is often used in diseases, such as Qi deficiency and fatigue, spleen deficiency diarrhea and so on, and has been well known by doctors. In recent years, scholars have a comprehensive understanding of the mechanisms in replenishing Qi, invigorating spleen and promoting water. However, Tao Hongjing first recorded that Astragali Radix membranaceus can " clear the evil blood between the five organs" . In Bencaojing Jizhu, this herbal medicine has the effect in promoting blood circulation at the same time. At present, traditional Chinese medicine often explains the mechanism of this herbal medicine in promoting blood circulation based on the theory of " replenishing Qi and activating blood circulation" and " blood circulation due to Qi circulation" , which however is not equivalent to the fact that this herbal medicine has no blood circulation effect. By summarizing the records of Astragali Radix membranaceus in the herbal literatures of the previous dynasties, it was found that its promoting blood circulation effect was widely used. In summary of the applications of traditional prescriptions and modern prescriptions in promoting blood circulation, Astragali Radix membranaceus can remove obstruction and activate blood circulation, activate blood and promote diuresis, activate blood circulation and strengthen the body resistance, which can best reflect the effect in activating blood circulation of this medicine. Modern pharmacology shows that Astragali Radix membranaceus has a good regulatory effect on the molecular mechanism of blood stasis pathological indexes by activating blood circulation. Due to no in-depth research, there is still room for study. Therefore, this paper thoroughly explores the mechanism of action of Astragali Radix membranaceus in promoting blood circulation by summarizing the effects of Astragali Radix membranaceus in literatures of previous dynasties and modern pharmacological studies, in order to expand the clinical application of Astragali Radix membranaceus and provide theoretical guidance for clinical treatment.

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-BarrVirus Associated Chronic Lymphocytic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus(EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as wellas role of EBV-miR-BHRF1-1 in p53 gene. @*Materials and Methods@#Quantitative reverse transcription–polymerase chain reaction and western blotting wereused to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. @*Results@#p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p <0.001) which was also an independent prognostic marker for overall survival (p=0.028;hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLLpatients after adjusted with International Prognostic Index for patients with CLL. We identifiedEBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressedluciferase reporter activity by specific interaction with the seed region within the p53 3-untranslated region. Discordance of p53 messenger RNA and protein expression wasassociated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1-1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosisand decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferationin cell lines. @*Conclusion@#This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our resultssupport the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLLwith p53 gene aberration.

Biological effects of carbon ion radiation combined with chemotherapy / 中华放射医学与防护杂志

Carbon-ion beam (CIB) is a high-linear energy transfer (LET) radiation. CIB is featured with more superior physical dose distribution (i.e., Bragg Peak) as compared to photon beam. In addition, it induces more double-bond break thus has higher relative biological effectiveness (RBE) as compared to photon beam. The combined use of chemotherapy and conventional photon radiotherapy has been widely used in the treatment of tumors. Chemotherapy is used concurrently with photonradiotherapy due to its radiosensitization. However, the radiosensitization effect of chemotherapy used with carbon-ion radiotherapy is controversial. In this article, we reviewed the previous studies of biological effects of the combination of carbon ion radiotherapy and chemotherapy in basic biological studies (including cytological and animal experiments) and clinical outcomes, and elaborated the biological effects.