An Exploratory Analysis of the Conditional Neurocognitive Function Failure Risk in Patients Receiving Whole Brain Radiotherapy for Brain Metastases on NRG Oncology CC001: Conditional Neurocognitive Toxicity Risk.

PURPOSE: We sought to estimate the conditional risk of development of neurocognitive function failure (NCFF) after whole brain radiotherapy (WBRT) for patients with brain metastases (BM) on NRG Oncology CC001. In addition, we aimed to determine if factors prognostic of NCFF at time of treatment remained relevant over time. MATERIALS/METHODS: We performed a post hoc analysis of 518 patients enrolled on NRG CC001 in which patients with BM were randomly assigned to WBRT + memantine or hippocampal-avoidant (HA-WBRT) + memantine. Life table method was used to calculate conditional monthly hazard rates and cumulative incidence was used to estimate rates of NCFF. Risk factors associated with NCFF were analyzed using cause-specific multivariable Cox proportional hazards modeling. RESULTS: The cumulative risk of development of NCFF by 6 months was 64.0% for the entire cohort. The greatest conditional monthly hazard rate of development of neurocognitive toxicity was 2-3 months post radiation (0.97, 95% CI 0.85-1.10); this rate significantly declined and then plateaued to 0.036 (95% CI: 0-0.11) by 8 months post treatment. For 2-month survivorship without cognitive failure, HA-WBRT (HR 0.74, P=0.033) and age ≤ 61 (HR 0.62, P=0.003) continued to be protective against cognitive toxicity. In addition, conditional cumulative incidence of development of NCFF was significantly reduced with HA techniques for patients living ≥ 2 months free of cognitive dysfunction (P=0.047). CONCLUSIONS: Our data highlight that the greatest risk for development of neurocognitive toxicity is within the first 3 months after treatment, and therefore strategies to mitigate toxicities should focus on this initial period. Moreover, the conditional risk of neurocognitive impairment significantly declines the longer patients live with preserved cognition. Importantly, these data can be used to inform patients on how their risks of development of NCFF can change over time.

Evaluating the sensitivity of EQ-5D-5L in patients with brain metastases: a secondary analysis of NRG CC001.

BACKGROUND: EuroQoL EQ-5D-5L is a commonly used measure of health-related quality of life in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D-5L is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes. METHODS: A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups. RESULTS: EQ-5D-5L mean index and VAS score changes between patients who had cognitive failure and those who had preserved cognition showed no statistically significant differences at any timepoint. In contrast, VAS changes at 4 months (1.61 vs -5.13, P = .05) and 6 months (8.17 vs -0.14, P = .04) were significantly improved in the patients who survived without intracranial progression. MDASI-BT cognitive factor scores were improved in the cohort of patients with preserved neurocognitive function at 2 months (1.68 vs 2.08, P = .05) and 4 months (1.35 vs 1.83, P = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status. CONCLUSION: EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a quality of life metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction. TRIAL REGISTRATION: NCT# 02360215.

Analysis of Acupoint Selection Rules of Acupuncture and Moxibustion in the Treatment of Temporomandibular Disorder Based on Data mining / 广州中医药大学学报

Objective To analyze the selection rules and characteristics of acupuncture and moxibustion in the treatment of temporomandibular disorder(TMD)based on data mining techniques.Methods Computerized search of major databases such as CNKI,Wanfang,VIP,and CBM from January 2002 to June 2022.After screening and standardized treatment of acupuncture prescriptions,data analysis was performed to explore the selection and characteristics of core acupoints.Results A total of 92 papers were included,and 108 valid prescriptions and 36 acupuncture points were extracted with a total frequency of 555 times.Among them,11 high-frequency acupoints in the top 10 of the total frequency were used,including Xiaguan(ST7),Hegu(LI4),Jiache(ST6),Tinggong(SI19),Yifeng(SJ17),Ashi,Zusanli(ST36),Quanliao(SI18),Shangguan(GB3),Fengchi(GB20),Tinghui(GB2),with a total of 481 times,accounting for 85.79%of the total frequency.The association rules showed a very strong correlation and co-occurrence between Xiaguan(ST7),Hegu(LI4),Jiache(ST6),Tinggong(SI19),and the cluster analysis yielded 4 core clusters.Conclusion Acupuncture and moxibustion for treatment of this disease mainly follows the principle of"the main treatment should reach where the meridians pass",and the core combination of selected points is:Xiaguan(ST7)-Hegu(LI4)-Jiache(ST6)-Tinggong(SI19).

Differential Diagnosis of Dynamic Contrast-Enhanced-MRI-Based Radiomics Model for Granulomatous Mastitis and Breast Cancer / 中国医学影像学杂志

Purpose To investigate the value of a radiomics model based on dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in the differential diagnosis of granulomatous mastitis and breast cancer.Materials and Methods The MRI data of 82 patients with granulomatous mastitis or breast cancer confirmed by pathology in Xiyuan Hospital of China Academy of Chinese Medical Sciences from February 2019 to January 2022 were retrospectively collected.Based on the first phase of DCE-MRI,the regions of interest(ROI)were delineated layer by layer by semi-automatic segmentation method and manual segmentation method,respectively.99 ROI were randomly assigned to 69 in training groups and 30 in test groups.The consistency difference between the two methods was compared.The original data extracted by the semi-automatic segmentation method were screened by correlation analysis and multi-factor Logistic regression.Six kinds of classifiers(Logistic regression,support vector machine,naive Bayes,decision tree,random forest,K nearest neighbor)were used to construct prediction models,and the differences in diagnostic efficiency,accuracy,sensitivity and specificity of each model were evaluated.Results A total of 99 lesions(n=37 cases with granulomatous mastitis and n=62 cases with breast cancer)were segmented from 82 patients.The radiomics data extracted by the two ROI segmentation methods had poor consistency between groups[Intraclass correlation coefficient=0.68(0.51,0.78)].Among the six prediction models constructed from the data extracted by the semi-automatic segmentation method,the diagnostic performance of the Logistic regression model and the support vector machine model was significantly better than those of other models,and the Logistic regression model had the best diagnostic performance and stability(training group:area under the curve 0.928,accuracy rate 0.855,sensitivity 0.837,specificity 0.885;test group:area under the curve 0.933,accuracy 0.833,sensitivity 0.895,specificity 0.727,respectively).Conclusion Radiomics based on DCE-MRI can provide high value for the differential diagnosis of granulomatous mastitis and breast cancer.The semi-automatic segmentation method is more recommended for the segmentation method of ROI.The prediction model constructed by Logistic regression and support vector machine shows better diagnostic efficiency and stability.

Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001.

BACKGROUND: Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases (BM). This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT. METHODS: An exploratory analysis of NRG CC001, a phase III trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated. RESULTS: The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58-0.97, P=0.03), whereas patients living < 4 months derived no significant neurocognitive benefit. Significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P=0.03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR=0.64, 95% CI: 0.48-0.85, P=0.002) compared to those with highest MDASI-BT scores (HR=1.24, 95% CI: 0.76-2.04, P=0.39). Tumor histology also had significant interaction (P=0.01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR=0.58, 95% CI: 0.43-0.77, P=0.0007) from HA-WBRT, in contrast to non-lung primary histology patients (HR=1.15, 95% CI: 0.78-1.50, P=0.48). CONCLUSIONS: Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.

Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker.

AIM: To validate pharmacodynamic responses to sodium-glucose co-transporter-2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9. METHODS: Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug-induced increases in urinary excretion of glucose, sodium and uric acid. RESULTS: This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (-4.1 mg/dL; P = 6 × 10-5 ), serum creatinine (+0.05 mg/dL; P = 8 × 10-4 ) and serum uric acid (-0.90 mg/dL; P = 5 × 10-10 ). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ~60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram-creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated glomerular filtration rate or age in those healthy individuals without diabetes with an estimated glomerular filtration rate of more than 60 mL/min/1.73m2 . CONCLUSIONS: Normalizing data relative to creatinine excretion will facilitate including data from males and females in a single analysis. Furthermore, because our ongoing pharmacogenomic study (NCT02891954) is conducted in healthy individuals, this will facilitate detection of genetic associations with limited confounding by other factors such as HbA1c and renal function.

Pharmacogenetics of SGLT2 Inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker.

Aim: SGLT2 inhibitors provide multiple benefits to patients with type 2 diabetes - including improved glycemic control and decreased risks of cardiorenal disease. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses. Methods: Canagliflozin (300 mg) was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses - including drug-induced increases in urinary excretion of glucose, sodium, and uric acid. Results: This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (-4.1 mg/dL; p=6x10), serum creatinine (+0.05 mg/dL; p=8×10 -4 ), and serum uric acid (-0.90 mg/dL; p=5×10 -10 ). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ∼60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram-creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated GFR, or age in these healthy non-diabetic individuals with estimated GFR>60 mL/min/1.73m 2 . Conclusions: Normalizing data relative to creatinine excretion will facilitate including data from males and females in a single analysis. Furthermore, because our ongoing pharmacogenomic study ( NCT02891954 ) is conducted in healthy individuals, this will facilitate detection of genetic associations with limited confounding by other factors such as age and renal function. Registration: NCT02462421 ( clinicaltrials.gov ). Funding: Research grants from the National Institute of Diabetes and Digestive and Kidney Diseases: R21DK105401, R01DK108942, T32DK098107, and P30DK072488.

Ciliatoside A, isolated from Peristrophe japonica, inhibits HBsAg expression and cccDNA transcription by inducing autophagy.

Hepatitis B surface antigen (HBsAg) loss and seroconversion are considered as an end point of a functional cure. Therefore, it is crucial to find new agents which could efficiently decrease HBsAg. Traditional herbal plants have been considered as an important source of new hepatitis B drugs development for their extensive use in antimicrobial and anti-inflammation. In this study, Peristrophe japonica, which could remarkably reduce HBsAg in the supernatant of HepG2.2.15 cells, was screened out for further extraction. Here, an active ethyl acetate fraction of Peristrophe japonica containing 34 sub-fractions was extracted. Subsequently, the monomeric compound Ciliatoside A was isolated and identified as a potential antiviral reagent with low cytotoxicity from Fraction 30. Ciliatoside A exhibited strong inhibition on intracellular and circulating HBsAg and HBV RNAs in HBV-infected cells and an HBV recombinant-cccDNA mouse model. The mechanistic study revealed that Ciliatoside A exhibited a potent anti-HBV effect through inducing autophagy-lysosomal pathway to autophagic degradation of HBc by activating AMPK-ULK1 axis and inhibiting mTOR activation. In summary, we have identified a novel antiviral compound Ciliatoside A isolated from Peristrophe japonica. This study may provide important direction and new ideas for the discovery of hepatitis B cure drugs.

Diagnostic value of CHA2DS2-VASc score combined with two serum factors for non-valvular atrial fibrillation complicated with ACI / 中华老年心脑血管病杂志

Objective To investigate the changes in serum levels of angiopoietin-like protein 4(ANGPTL4)and ubiquitin carboxyl terminal hydrolase-1(UCH-L1),and CHA2DS2-VASc score in patients with non-valvular atrial fibrillation(NVAF)and acute cerebral infarction(ACI),and their diagnostic value.Methods A total of 162 NVAF patients treated in our hospital from Janu-ary 2021 to January 2023 were enrolled and divided into a combined group(45 cases)and a non-combined group(117 cases)according to having ACI or not.General clinical information,CHA2DS2-VASc scores,and serum levels of ANGPTL4 and UCH-L1 were collected and detected.Spearman correlation analysis was applied to evaluate the correlation of ANGPTL4,UCH-L1 and CHA2DS2-VASc score.Multivariate logistic regression analysis was performed to identify the in-fluencing factors of NVAF combined with ACI.ROC curve was plotted to evaluate the diagnostic value of serum ANGPTL4,UCH-L1,and CHA2DS2-VASc score for NVAF combined with ACI.Results The ANGPTL4 level was significantly lower,and the UCH-L1 level and CHA2DS2-VASc score were obviously higher in the combined group than the non-combined group(P＜0.05).In the patients with NVAF combined with ACI,serum ANGPTL4(r=-0.548,P＜0.05)and UCH-L1(r=0.400,P＜0.05)levels were negatively and positively correlated with CHA2DS2-VASc score,respectively.ANGPTL4,UCH-L1 and CHA2DS2-VASc were the risk fac-tors for ACI in NVAF patients(P＜0.05,P＜0.01).The AUC value of combined serum ANGPTL4 and UCH-L1 levels and CHA2DS2-VASc score for diagnosing NVAF complicated with ACI was 0.926(95％CI:0.874-0.961).Conclusion Combined detection of serum AUCH-L1 and NGPTL4 levels and CHA2DS2-VASc score can significantly improve the diagnostic value of NVAF patients with ACI.

Correlation analysis of adverse outcomes for the selective reduction of twin pregnancies.

BACKGROUND: Due to the extensive development of assisted reproductive technology, the number of twin pregnancies has increased significantly over recent decades. Twin pregnancy is the most representative type of multiple pregnancies and is associated with high infant morbidity and mortality. Perinatal complications of twin pregnancy are also markedly increased compared with those of single pregnancy. Transabdominal selective reduction (SR) is a remedial intervention. This study aimed to research the adverse outcomes of transabdominal selective reduction of twin pregnancy and the correlation between the reduction week and pregnancy outcomes. OBJECTIVE: The purpose of this study was to examine the adverse outcomes of the transabdominal selective reduction of twin pregnancy and the correlation between the reduction week and pregnancy outcomes. METHODS: A retrospective cohort study of the transabdominal reduction of twin pregnancy was conducted in a single prenatal diagnosis medical centre from September 2012 to October 2020. According to chorionicity, women with twin pregnancies were divided into 2 groups: dichorionic (DC) twin pregnancies and monochorionic (MC) twin pregnancies. Women with DC twin pregnancies underwent potassium chloride reduction, and those with MC twin pregnancies underwent radiofrequency ablation (RFA). The reduction indications included pregnancy complications, foetal abnormalities, and maternal factors. The perinatal outcomes of different chorionic twins after reduction were analysed. Each foetus with an adverse outcome was included. The relative relationship between the reduction weeks and delivery weeks of twins was examined by correlation analysis. RESULTS: A total of 161 women were included in this study. A total of 112 women had DC twin pregnancies, and 49 women had MC twin pregnancies. Preterm delivery rates were significantly higher in the MC twin reduction group than in the DC twin reduction group prior to 37 weeks (53.1% vs. 29.5%, P = 0.004). The mean gestational age at delivery of the foetuses in the DC twin group that underwent SR was significantly older than that of those in the MC twin group that underwent SR (36.9 ± 4.0 vs. 33.5 ± 6.6 weeks, P = 0.001). The number of DC twins that underwent SR and were delivered after 37 weeks was obviously greater than that of the MC twins that underwent SR (70.5% vs. 46.9%, P = 0.004). The foetal survival rate was 95.5% in the DC twin reduction group and 77.6% in the MC twin reduction group. If the indication of TTTS was not included, there was no significant difference in the foetal survival rate of the DC and MC twin reduction groups (95.5% vs. 86.2%, P = 0.160). Cotwin death 1 week after reduction was greater in the MC group (6.1% vs. 0%, P = 0.027). Compared to other indications, this finding indicated that a significantly lower proportion of women remained undelivered after selective reduction with the indication of TTTS. There was a significant negative correlation between the reduction weeks and delivery weeks of the two groups (P < 0.01), and the best opportunity for reduction was before 22 weeks of gestation. CONCLUSION: These findings highlighted an obviously negative correlation between the reduction week and delivery week. The transabdominal selective reduction of twin pregnancy should be considered for a lower rate of miscarriage or premature delivery if the reduction week takes place earlier in pregnancy. The rate of preterm delivery was the lowest when transabdominal selective reduction was completed before 22 weeks of gestation. Compared with other RFA indications, a higher rate of premature delivery was shown for MC twins with a reduction indication of TTTS. TTTS with sIUGR might be one of the reasons for the adverse outcomes of reduction for MC twin pregnancy.

Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial / 中华肿瘤杂志

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

A Prospective Multicenter Study of the Chinese Scoring System for Hepatitis B Liver Failure.

Objective: To evaluate the clinical utility of a Chinese scoring system for hepatitis B liver failure in a prospective and multicenter study. Methods: Clinical data for 1,143 patients with hepatitis B liver failure who had been followed up for a minimum of 6 months were collected from seven liver disease centers across China. The disease severity and prognosis for the patients were predicted using the Chinese scoring system and compared to those predicted with the model for end-stage liver disease (MELD) score, MELD-Na score, and Child-Turcotte-Pugh (CTP) score. Results: The Chinese scoring system was more effective at predicting the outcomes of survival and mortality than the MELD score. In the peak disease stage, the area under the receiver operating characteristic curve for the Chinese scoring system was 0.954, significantly higher than that (0.896) for the MELD scoring system (P < 0.001). The positive prediction at 30, 90, and 180 days with the Chinese scoring system was 0.764 (95% CI: 0.714-0.808), 0.731 (95% CI: 0.694-0.769), and 0.724 (95% CI: 0.679-0.765), also significantly higher than that with the MELD, MELD-Na, and CTP scores (P < 0.001). In addition, the Chinese scoring system was superior to the MELD, MELD-Na, and CTP scores (P < 0.001) at predicting the prognosis of patients with hepatitis B liver failure at both 30 and 180 days. Conclusion: The Chinese scoring system demonstrated superior performance to the three established scoring systems in assessing the severity and outcomes of hepatitis B liver failure in this cohort.

Camel nanobodies broadly neutralize SARS-CoV-2 variants

With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two VHH nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of [≥]5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants. One-Sentence SummaryDromedary camel (Camelus dromedarius) VHH phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.

Patterns of Failure in Triple Negative Breast Cancer Patients in an Urban, Predominately Black Population.

Triple negative breast cancers (TNBC) behave more aggressively than hormone-receptor positive breast cancers. They are also known preferentially to affect young black women, often leading to poorer outcomes compared with those for white women. We sought to evaluate the comprehensive patterns of failure associated with treatment for TNBC at an urban institution with a predominantly black population and to assess the impact of social determinants of health on treatment failure. A retrospective review of TNBC patients treated from 2005 to 2015 was conducted. Detailed patient, tumor, and treatment characteristics and information on patterns of failure were included. With a median follow-up of 46 months, 32 (16%) documented failures occurred. Locoregional failures comprised 84% of failure patterns whether isolated or in combination with distant failure. Treatment failure was associated with insurance type and smoking status, as well as several tumor characteristics. On multivariate analysis, pathologic nodal staging was the most significant predictor of treatment failure. In contrast to previous studies, we found that black women had higher overall survival than white women, but race was not associated with differences in recurrence patterns or with likelihood of treatment failure. Regardless of race, of the patients who recurred, 53% failed in distant and locoregional sites simultaneously, with an additional 34% failing locally only. These results highlight the need for aggressive local therapies in high-risk patients and suggest a need for improved follow-up focusing on detecting locoregional failures. Multidisciplinary care is essential in the management of these patients at time of failure.

Spectrum analysis of gene mutations in retinitis pigmentosa and cone-rod dystrophy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the gene mutation spectrum of autosomal recessive retinitis pigmentosa(ARRP)pedigrees and cone-rod dystrophy(CORD)pedigrees in Ningxia region of China. <p>METHODS:Totally 35 ARRP pedigrees and 18 CORD pedigrees were included in Ningxia Eye Hospital from September 2016 to February 2020. Peripheral venous blood samples of the proband were collected for targeted capture enrichment and high-throughput sequencing using a genetic retinal disease capture chip that contain 232 pathogenic genes. Online analysis software was used to predict the pathogenicity of suspicious gene variation, and Sanger sequencing was used to analyze the co-segregation of the family members. <p>RESULTS: Totally 16 pathogenic genes were confirmed in 35 ARRP pedigrees, the mutations rate of RP1 gene was the highest, accounting for 14%(5/35), following were ABCA4, CRB1 and EYS gene, accounted for 11%(4/35); 18 CORD pedigrees carried 10 pathogenic genes. The mutation rate of ABCA4 gene was the highest, accounting for 28%(5/18), followed by ALMS1, PROM1, RPE65, USH2A gene, accounting for 11%(2/18). There were 5 co-exist disease-causing genes in ARRP and CORD pedigrees, which were ABCA4, CLN3, CRB1, PROM1, NRL, accounting for 42%(22/53).<p>CONCLUSION: There are similarities and crossover in the phenotype of ARRP and CORD. The pathogenic genes were overlaped. The most common overlaping gene between the two diseases is ABCA4.

Related factors of troublemaking among patients with mental disorders caused by amphetamine-type stimulants / 四川精神卫生

ObjectiveTo explore the related factors of troublemaking behaviors among patients with mental disorders induced by amphetamine-type stimulants （ATS）， and to provide references for the formulation of relevant intervention measures for ATS-induced mental disorders. MethodsA total of 105 patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for ATS-induced mental disorders were included， and classified into troublemaking group and non-troublemaking group. The general demographic data and clinical data of the selected individuals were collected， and all patients were assessed using Social Support Rating Scale （SSRS）. Then univariate analysis and multivariate Logistic regression model were used to screen the related factors of troublemaking behaviors. ResultsThe scores of SSRS， objective support dimension and social support utilization dimension were significantly lower in troublemaking group than those in non-troublemaking group， with statistical differences ［（24.10±6.59） vs. （28.94±5.59）， t=3.364， P=0.001； （5.50±1.96） vs. （8.20±2.13）， t=5.183， P<0.01； （4.60±2.26） vs. （6.28±1.90）， t=3.435， P=0.001］. Multivariate Logistic regression analysis showed that male （OR=6.061， P=0.014） was a risk factor， while high social support level （OR=0.873， P=0.018） was the protective factor for troublemaking behaviors among patients with ATS-induced mental disorders. ConclusionPatients with ATS-induced mental disorders of the males and with low social support level are at high risk of troublemaking behaviors.

Small ubiquitin-like modifier proteins specific protease 3 in microglia participating in the early progression of photothrombosic ischemic stroke mice model / 解剖学报

Objective To investigate the expression of small ubiquitin-like modifier proteins specific protease 3 (SENP3) in microglia of mice with ischemic stroke and its relationship with the progression of ischemic stroke. Methods The experimental animals were divided into control group, ischemic stroke day 1 group and ischemic stroke day 7 group (3 mice per group). The expression of inducible nitric oxide synthase (iNOS), argniase-1 (ARG-1), SENP3 and c-Jun N-terminal kinase (JNK) phosphorylation levels in the striatum were detected by immunoblotting. The expression of iNOS and ARG-1 in mouse striatum microglia was detected by immunofluorescence double labeling. Results Compared with the control group, the expression of SENP3 and the phosphorylation level of JNK in the ischemic stroke group increased significantly, and the expression of the marker iNOS of Ml type microglia increased significantly. The expression of the marker ARG-1 of M2 type microglia increased significantly in the day 7 group of ischemic stroke. The immunofluorescence double-labeled result of striatum ionized calcium binding adapter molecule 1 (Ibal) and iNOS, Ibal and ARG-1 were consistent with the result of immunoblotting. Conclusion In the early stage of ischemic stroke, the expression of SENP3 in microglia increases, which promote the cerebral inflammatory response by affecting the level of JNK phosphorylation and the polarization of microglia, and participate in the progression of ischemic stroke.

Analysis of monitoring results of disinfection quality in child care institutions in Qingpu District of Shanghai， 2016-2018 / 上海预防医学

Objective:To determine the disinfection effect in child care institutions in Qingpu District of Shanghai， and provide evidence for improving the disinfection quality and preventing and controlling infectious diseases. Methods:According to the monitoring program of disinfection quality in child care institutions in Shanghai， disinfection quality was monitored for 3 years. Results:A total of 979 samples were monitored in the consecutive three years， in which 895 samples were qualified with a total qualification rate of 91.42%. The qualification rate of air samples was 100.00%， while the rate of staff hand samples was the lowest， with an average of 79.60%. During 2016-2018， the difference among the annual qualification rates was statistically significant（χ2=23.809，P<0.05）， whereas it was not significant in the rates between public institutions and private ones （χ2=0.141，P>0.05）. Conclusion:The quality of preventive disinfection in child care institutions in Qingpu District is generally good， but the disinfection of tableware， surface of objects and staff needs to be further improved.

A comparative study of dose distribution of prostate IMRT between IMRT and VMAT models using knowledge-based planning / 中华放射肿瘤学杂志

Objective:To compare the dosimetric difference between knowledge-based planning (KBP) volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) models for predicting the dose distribution during IMRT, aiming to investigate the feasibility of VMAT model to predict the IMRT plans.Methods:Fifty prostate cancer patients who had completed radiotherapy were selected. Manual planning was performed on each selected patient to generate the corresponding IMRT and VMAT plans. The IMRT and VMAT manual plans of the 40 randomly-selected patients were adopted to generate the KBP VMAT and IMRT models. The remaining 10 patients were utilized to predict IMRT plans. VMAT library-derived IMRT model (V-IMRT) and IMRT library-derived IMRT model (I-IMRT) were generated. Dosimetric parameters related to organ-at-risks (OARs) and planning target volume (PTV) were statistically compared among the manual IMRT (mIMRT), V-IMRT and I-IMRT plans.Results:Compared with the mIMRT plan, I-IMRT could significantly better control D max of the PTV ( P=0.039), whereas V-IMRT and I-IMRT plans could better protect the bladder and bilateral femoral heads (both P<0.05). V-IMRT plan could better protect the D max of bilateral femoral heads and the D 15% of the right femoral head (both P<0.05), whereas no significant difference was observed in other OARs and PTV (all P>0.05). Conclusions:Compared with the manual plans, KBP IMRT plan has significant advantages in protecting the OARs. KBP VMAT and IMRT models are both feasible in clinical practice, which yield equivalent accuracy for predicting IMRT plan.

Baicalin protects against 17α-ethinylestradiol-induced cholestasis via Sirt1/HNF-1α/FXR pathway / 中国药理学与毒理学杂志

OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis (EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol (EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum bio?markers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids (BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expres?sion of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat and Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflamma?tion through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.