Endoplasmic Reticulum-Targeted Carbon Monoxide Photoreleaser for Drug-Induced Hepatotoxicity Remediation.

The alleviation of drug-induced liver injury has been a long-term public health concern. Growing evidence suggests that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of drug-induced hepatotoxicity. Therefore, the inhibition of ER stress has gradually become one of the important pathways to alleviate drug-induced liver injury. In this work, we developed an ER-targeted photoreleaser, ERC, for controllable carbon monoxide (CO) release with a near-infrared light trigger. By employing peroxynitrite (ONOO-) as an imaging biomarker of hepatotoxicity, the remediating effect of CO was mapped upon drug acetaminophen (APAP) challenge. The direct and visual evidence of suppressing oxidative and nitrosative stress by CO was obtained both in living cells and in mice. Additionally, the ER stress inhibiting the effect of CO was verified during drug-induced hepatotoxicity. This work demonstrated that CO may be employed as a potent potential antidote for APAP-related oxidative and nitrative stress remediation.

Bio-orthogonally Activatable Fluorescent Probe for Specific Imaging of Myeloid Cell Leukemia 1 Protein.

The antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) has been increasingly identified as a promising potential therapeutic target attributed to its critical regulation effect in diverse cellar physiopathological events. Current fluorescence imaging strategies tend to be susceptible to the cellular microenvironment, and straightforward mapping of Mcl-1's level variation remains challenging. In this paper, an activatable "off-on" fluorescence strategy for Mcl-1 specific labeling was presented based on bio-orthogonal chemistry by introducing tetrazine-functionalized borondipyrromethene (TB) as a fluorescent reporter and trans-cyclooctyne-derived indole-2-carboxylic acid (TI) as an Mcl-1 targeting moiety. With the click pair of TB and TI, the Mcl-1 expression level in vitro and in vivo was successfully mapped straightforward. Also, the level changes of Mcl-1 upon drug challenge were demonstrated. This work provides a robust fluorescence strategy for Mcl-1 in situ imaging, and the results would further facilitate the comprehensive revelation of the Mcl-1 biological effect.

Controlling average number of photons received per biomass to promote the growth of Synechocystis sp. PPC 6803.

To investigate the actually received light of cells in the photo bioreactor, a light attenuation model of Synechocystis sp. PCC 6803 was established. The relationship between the average number of photons received per biomass (APRPB) and the growth of cell was analyzed. The results demonstrated, Cornet model was accurately fitted with the light attenuation of Synechocystis sp. PCC 6803 and the cell growth rate was affected by APRPB. When the value of APRPB is 3.2 µmol g-1 s-1, the cell have the maximum light efficiency. A maximum specific growth rate of 0.05 h-1 was achieved with APRPB from 3.2 to 12.8 µmol g-1 s-1. After 156 h cultivation, compared to cells cultured under constant light [light intensity: 100 and 1800 µmol/(m2 s)], the DCW under controlled light intensity (light intensity increasing with the cell density) was higher by 79.1% and 20.0%, respectively. This study indicated that APRPB could be used as a light intensity regulation criterion to improve cell production despite different types of reactor and cell density, which provided a theoretical basis for improving the biomass yield of Synechocystis sp. PCC 6803 or other photosynthetic auto-trophic organism.

Development and Experimental Research of VFTO Measuring Sensor.

Very fast transient overvoltage (VFTO) generated by an operating disconnector is one of the main reasons for electromagnetic disturbance in gas-insulated switchgear (GIS) substations. Generally, the amplitude of VFTO can be used as one of the references for the insulation design of GIS primary electric power equipment, so it is necessary to obtain its accurate amplitude. In this study, a new VFTO measuring sensor is developed and its measurement performance is demonstrated through hundreds of operations by a disconnector in a 220 kV GIS test circuit. The validation shows that the low cut-off frequency of the new VFTO measuring sensor has been greatly expanded to 0.01 mHz, which is improved by about 50% compared with the old sensor. The measurement accuracy of amplitude of VFTO micro-pulse improves greatly by about 80% compared with the old one. Thus, the new VFTO measuring sensor can fully meet the measurement needs of trapped charge voltage, power frequency voltage, and high-frequency transient voltage in VFTO waveform. It can be used to provide more accurate data support for insulation design of GIS primary power electric equipment in extra-high voltage (EHV) and ultra-high voltage (UHV) GIS substations.

Power-frequency magnetic fields at 50 Hz do not affect fertility and development in rats and mice.

In the present study, the effects of power-frequency magnetic fields (PF-MF) on fertility and development were investigated in rats and mice. Adult Sprague-Dawley rats and C57BL/6J mice were divided into four groups: a sham exposure group and 30-µT, 100-µT and 500-µT PF-MF exposure groups. The rats were exposed for 24 weeks, and the exposure time for mice ranged from 18 d to 12 weeks, dependent on the different investigated end points. The rats and mice were exposed for 20 h/d. Plasma hormone levels in rats and mice were analyzed. Furthermore, pregnancy rates and implanted embryos were recorded in pregnant mice. Finally, the neonatal growth of mice was evaluated. The results showed that none of the three intensities affected the body weight and paired ovary weight in female rats. Meanwhile, none of the three intensities affected the body weight, weights of paired testes, weights of paired epididymis and sperm count in male rats. Similarly, no significant differences were found in plasma sex hormone levels between the different PF-MF exposure groups and the sham exposure group. In addition, the pregnancy rates and implanted embryos were not significantly different between the four groups. Moreover, PF-MF exposures had no effects on either the number of fetuses in pregnant mice or the growth and development of neonatal mice.

Structural Modulation from 1D Chain to 3D Framework: Improved Thermostability, Insensitivity, and Energies of Two Nitrogen-Rich Energetic Coordination Polymers.

Two new energetic coordination polymers (CPs) [Pb(BT)(H2O)3]n (1) and [Pb3(DOBT)3(H2O)2]n·(4H2O)n (2) with 1D and 3D structures were synthesized by employing two rational designed ligands, 1H,1'H-5,5'-bitetrazole (H2BT) and 1H,1'H-[5,5'-bitetrazole]-1,1'-diol ligands (DHBT), respectively. Thermal analyses and sensitivity tests show that the 3D architecture reinforces the network of 2 which has higher thermal stability and lower sensitivity than that of 1. Through oxygen-bomb combustion calorimetry the molar enthalpy of formation of 2 is derived to be much higher than that of 1 as well as the reported CPs. Herein, more importantly, the heats of detonation (ΔHdet) were calculated according to the decomposition products of TG-DSC-MS-FTIR simultaneous analyses for the first time. The calculated results show that ΔHdet of 2 is 23% higher than that of 1. This research demonstrates that 3D energetic CP with outstanding energetic properties can be obtained through efficient and reasonable design.

[Analysis of results of endoscopic screening of esophageal, gastric cardia and gastric cancers in high risk population].

OBJECTIVE: To summarize the results of endoscopic screening of esophageal, gastric cardiac and gastric cancers in the high-risk population, and analyze the influencing factors such as age, gender and biopsy rate on their detection and early diagnosis rates. METHODS: Nine high incidence cities and counties of esophageal cancer in Henan province were included in this study. People aged 40-69 years were set to the target population. Excluding contraindications for gastroscopy, in accordance with the national technical scheme of early cancer diagnosis and treatment, gastroscopic screening and biopsy pathology for human esophageal, cardiac and gastric cancers were carried out. RESULTS: During the 3-year period, a total of 40 156 subjects were screened. Among them, 18 459 cases of various precancerous lesions (46.0%) were detected. The cancer detection rate was 2.3% (916 cases), including 763 cases of early cancers. The diagnosis rate of early cancers was 83.3%. Precancerous lesions were detected in 9297 cases (23.2%) for esophagus and 9162 cases (22.8%) for gastric cardia as well as stomach, respectively. CONCLUSIONS: The results of this study demonstrate that endoscopic screening is feasible for early detection, diagnosis and treatment of esophageal, gastric cardia and gastric cancers among high risk population in high incidence area. Exploration analysis of relevant affecting factors may help to further improve the screening project for early diagnosis and treatment of those cancers.

Current role of magnetic resonance imaging on assessing and monitoring the efficacy of phototherapy.

Phototherapy, also known as photobiological therapy, is a non-invasive and highly effective physical treatment method. Its broad use in clinics has led to significant therapeutic results. Phototherapy parameters, such as intensity, wavelength, and duration, can be adjusted to create specific therapeutic effects for various medical conditions. Meanwhile, Magnetic Resonance Imaging (MRI), with its diverse imaging sequences and excellent soft-tissue contrast, provides a valuable tool to understand the therapeutic effects and mechanisms of phototherapy. This review explores the clinical applications of commonly used phototherapy techniques, gives a brief overview of how phototherapy impacts different diseases, and examines MRI's role in various phototherapeutic scenarios. We argue that MRI is crucial for precise targeting, treatment monitoring, and prognosis assessment in phototherapy. Future research and applications will focus on personalized diagnosis and monitoring of phototherapy, expanding its applications in treatment and exploring multimodal imaging technology to enhance diagnostic and therapeutic precision and effectiveness.

NIR-II light therapy improves cognitive performance in MPTP induced Parkinson's disease rat models: A preliminary experimental study.

Cognitive impairment is an important component of non motor symptoms in Parkinson's disease (PD), and if not addressed in a timely manner, it can easily progress to dementia. However, no effective method currently exists to completely prevent or reverse cognitive impairment associated with PD. We therefore aimed to investigate the therapeutic effect of near-infrared region II light (NIR-II) region illumination on cognitive impairment in PD through behavioral experiments (water maze and rotary rod) and multiple fluorescence immunohistochemistry techniques. The 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced group was compared with the MPTP- untreated rat group, showing a significant reduction in escape latency and significant increase in the fall latency in the MPTP-treated group. The horizontal analysis results indicated that NIR-II phototherapy improved the learning and cognitive abilities as well as coordination and balance abilities of rats. Post-treatment, the MPTP rats showed significantly shortened, escape latency, prolonged target quadrant residence time, and prolonged fall latency compared with pre-treatment. The longitudinal analysis results reaffirmed that NIR-II phototherapy improved the learning and cognitive abilities as well as coordination and balance abilities of rats. The multiple fluorescence immunohistochemistry analysis trend plot showed that the activated microglia and astrocytes in the hippocampus were highest in MPTP-induced PD untreated group, moderate in MPTP-induced PD treatment group, and lowest in the control group. Our data indicates that NIR-II illumination improves learning and cognitive impairment as well as coordination and balance abilities in PD rats by downregulating the activation of microglia and astrocytes in the hippocampus.

Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer.

Inter- and intra-tumor heterogeneity is a major hurdle in primary liver cancer (PLC) precision therapy. Here, we establish a PLC biobank, consisting of 399 tumor organoids derived from 144 patients, which recapitulates histopathology and genomic landscape of parental tumors, and is reliable for drug sensitivity screening, as evidenced by both in vivo models and patient response. Integrative analysis dissects PLC heterogeneity, regarding genomic/transcriptomic characteristics and sensitivity to seven clinically relevant drugs, as well as clinical associations. Pharmacogenomic analysis identifies and validates multi-gene expression signatures predicting drug response for better patient stratification. Furthermore, we reveal c-Jun as a major mediator of lenvatinib resistance through JNK and ß-catenin signaling. A compound (PKUF-01) comprising moieties of lenvatinib and veratramine (c-Jun inhibitor) is synthesized and screened, exhibiting a marked synergistic effect. Together, our study characterizes the landscape of PLC heterogeneity, develops predictive biomarker panels, and identifies a lenvatinib-resistant mechanism for combination therapy.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

[Analysis of cancer incidence and mortality in Henan province, 2009].

OBJECTIVE: To analyze the cancer incidence and mortality of Henan province in 2009. METHODS: On basis of the criteria of data quality from the National Central Cancer Registry (NCCR), data from 6 registries in Henan province were evaluated, covering 6 061 564 people, accounting for 6.45% of the total population in Henan in 2009. There were 3 104 991 people of males, and 2 956 573 people of females. The incidence, mortality, 10 most common cancers, constitution and cumulative rate (0-74 years old) were then calculated. The age-standardized rate was calculated and adjusted by the Chinese standard population in 1982 as well as the Segi's world standard population. RESULTS: There were 12 091 new diagnosed cancer and 8040 death cases registered in Henan province in 2009. The rate of pathological diagnosis was 68.2% (8246/12 901) and only 1.75% (2116/12 901) had death certificates. The ratio of mortality and incidence was 0.66 (8040/12 091). The incidence rate was 199.47/100 000 (12 091/6 061 564) in total, and it was 216.36/100 000(6718/3 104 991) in males and 181.73/100 000(5373/2 956 573) among females. The standardized incidence by Chinese population was 126.50/100 000 and it was 166.08/100 000 by world's population. The cumulative rate was 19.95% between 0 and 74 years old. The incidence was the highest in Linzhou city, whose standardized incidence was 156.87/100 000 by Chinese population and the incidence was the lowest in Shenqiu city, whose standardized incidence was 104.82/100 000 by Chinese population. The morphology verified cases accounted for 68.2% (8246/12 091), death certification cases only accounted for 1.75% (2116/12 091), and mortality to incidence ratio was 0.66 (8040/12 091). The crude incidence in cancer registration areas of Henan province was 199.47/10 000 (12 091/6 061 564), 216.36/10 000(6718/3 104 991) for males, 181.73/10 000 (5373/2 956 573) for females, age-standardized incidence rates by Chinese standard population and by world standard population were 126.50/10 000 and 166.08/10 000 with cumulative incidence rate (0-74 age years old) of 19.95%. The crude mortality in cancer registration areas of Henan province was 132.64/100 000 (8040/6 061 564), separately 160.58/100 000 (4986/3 104 991) for males and 103.30/10 000 (3054/2 956 573) for females. The age-standardized mortality rates by Chinese standard population and by world's standard population were 78.41/10 000 and 107.49/10 000. The cumulative mortality rate (0-74 age years old) was 12.18%. The mortality rate was the highest in Linzhou city, whose standardized rate was 93.35/100 000 by Chinese population, and the lowest mortality rate was in Yuzhou city, whose standardized rate was 67.95/100 000. The most common cancers were lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum cancer, brain nervous system cancer, colon cancer, cervical cancer and uterus cancer, all of which accounted for 82.23% (9943/12 091) of the registered cancers.Lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, rectum cancer, brain nervous system cancer, pancreas cancer, colon cancer and gallbladder carcinoma were the major causes for the death, accounting for 86.30% (6938/8040) of all cancer deaths. CONCLUSION: Both incidence and mortality of cancer in Henan province were lower than the level in China, prevention and control should be implemented based on practical situation.

Diagnostic value of combined magnetic resonance imaging techniques in the evaluation of Parkinson disease.

Background: The incidence of Parkinson disease (PD) has been increasing each year. The development of new magnetic resonance imaging (MRI) technology can help understand its pathogenesis and identify more effective imaging-based biological indicators. Methods: The clinical and MRI imaging data of 40 patients with PD and 40 healthy controls were analyzed. All participants underwent susceptibility-weighted imaging (SWI), neuromelanin-sensitive magnetic resonance imaging (NM-MRI), and T2*mapping sequence examination. The diagnostic value of single and combined multiparameter indicators was analyzed using the receiver operating characteristic curve. Results: Compared with the healthy control group, the PD group showed significant differences in the disappearance of bilateral "swallow tail sign", the distribution volume of melanocytes in the substantia nigra and the smaller volume in the bilateral substantia nigra, the maximum signal of the locus coeruleus and the smaller and average volume in the bilateral substantia nigra, and the values of T2* and R2* in the bilateral substantia nigra (P<0.01). The maximum and smaller value and the average value of the bilateral locus coeruleus signal were negatively correlated with the disease course duration (P<0.05), and the smaller distribution volume of the melanin neurons in the bilateral substantia nigra was negatively correlated with Hoehn and Yahr (H-Y) grade (P<0.05). In the joint diagnosis with multiple indicators, some composite parameters were found to be negatively correlated with H-Y grading (P<0.05), while others were negatively correlated with disease course duration (P<0.05). Joint use of multiple parameter indicators greatly improved diagnostic efficacy [area under the curve (AUC) =0.958]. Conclusions: The distribution volume of melanin in substantia nigra and the maximum value of locus coeruleus signal may be the biological imaging indicators for the early diagnosis, severity, and follow-up evaluation of PD. Compared with a single indicator, composite indicators used in combination with multiple techniques have a significantly better diagnostic efficacy for PD.

Fear of COVID-19 among cancer patients in Henan Province, Central China: causes, results, and coping factors.

Objectives: Cancer patients exhibit fear of COVID-19, which could lead to serious consequences. However, minimal information is available about the effect of the COVID-19 pandemic on the mental health of cancer patients. Therefore, this study aims to examine the fear level of COVID-19 among cancer patients in Henan Province, Central China and to identify its causes, results, and coping factors. Methods: An online survey was conducted among 1,067 cancer patients. The participants reported their individual fear level of COVID-19, risk of COVID-19 infection, risk of death from COVID-19, COVID-19 vaccination concerns, influence level of COVID-19 pandemic on their disease treatment, loneliness due to COVID-19, economic burden from COVID-19, quality of life, safety behavior, information regarding COVID-19 vaccination, psychological guidance, physical activities, and demographic characteristics. Chi-square and cumulative logistic regression were used to determine the predictors of COVID-19 fear level. Results: This study indicates that cancer patients report moderate fear level of COVID-19 in Central China (66.9%). The six cause factors (risk of COVID-19 infection, risk of death from COVID-19, COVID-19 vaccination concerns, influence level of COVID-19 pandemic on disease treatment, loneliness due to COVID-19, and economic burden from COVID-19) were positively associated with COVID-19 fear level. Three coping factors (information regarding COVID-19 vaccination, psychological guidance, and physical activities) were negatively associated with COVID-19 fear level. COVID-19 fear level was negatively associated with quality of life and positively associated with safety behavior. Conclusion: Our results suggest that governments should improve access to personalized vaccine counseling and psychological guidance by undertaking the responsibility of patients' attending physicians and increasing publicity. Physical activities should be included in the treatment program to help cancer patients better recover their physical and mental health.

Prediction of Clinical Molecular Typing of Breast Invasive Ductal Carcinoma Using 18F-FDG PET/CT Dual-Phase Imaging.

RATIONALE AND OBJECTIVES: To investigate the diagnostic value of Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (18F-FDG PET/CT) dual-phase imaging for the different molecular subtypes of invasive ductal carcinoma of the breast. MATERIALS AND METHODS: Clinical imaging data of 164 women with invasive ductal carcinoma of the breast confirmed by pathology who underwent 18F-FDG PET/CT dual-phase imaging were retrospectively analyzed. The maximum standard uptake values (SUVmax) of the early and delayed phases of the lesion were measured and recorded as SUVmax1 and SUVmax2, respectively, and the retention index (RI) was calculated. We analyzed the change rule of SUVmax1, SUVmax2, and RI for the different molecular subtypes and molecular marker expression groups. The diagnostic threshold of different molecular marker expression status was determined using receiver operating characteristic curve analysis. RESULTS: SUVmax1 and SUVmax2 were highest in the TNBC group and lowest in the luminal A group (p<0.001). TNBC and HER2 overexpression groups had higher RI than the luminal A and B groups (p<0.001), with no significant difference between the TNBC and HER2 overexpression groups or between the luminal A and B groups (p=0.640 and 0.345, respectively). The ER- and PR-negative groups had significantly higher SUVmax1, SUVmax2, and RI than the PR-positive group (p<0.001). The HER2-positive group had higher SUVmax1 and SUVmax2 than the negative group (p<0.001). The Ki67 overexpression group had higher SUVmax1 and SUVmax2 levels than the low expression group (p<0.001). There was no significant difference in RI between HER2-positive and negative groups or between Ki67 high and low expression groups (p=0.904 and 0.216, respectively). For ER-negative and positive expression status, the maximum area under the curve (AUC) of SUVmax2 was 0.852, diagnostic threshold was 10.87, sensitivity was 79.6%, and specificity was 74.5%. For PR-negative and positive expression status, the AUC of SUVmax2 was 0.858, diagnostic threshold was 10.45, sensitivity was 83.1%, and specificity was 75.3%. For HER2-negative and positive expression status, the AUC of SUVmax1 was 0.714, diagnostic threshold was 9.28, sensitivity was 79.6%, and specificity was 60.9%. For Ki67 high- and low expression status, the AUC of SUVmax2 was 0.915 at maximum, diagnostic threshold was 10.21, sensitivity was 83.4%, and specificity was 93.9%. CONCLUSION: 18F-FDG PET/CT dual-phase imaging facilitates the prediction of the expression of molecular markers and subtypes of invasive ductal carcinoma of the breast and the development of more tailored treatment plans for patients with this disease.

Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction.

Objective: This study aimed to investigate the effect of Edaravone Dexborneol (ED) on impaired learning and memory in docetaxel (DTX)-treated rats using cognitive behavior assessments and magnetic resonance diffusion tensor imaging (DTI). Materials and methods: In total, 24 male Sprague-Dawley rats were divided into control, low-dose DTX (L-DTX) model, and high-dose DTX(H-DTX) model groups, with eight rats in each group, numbered 1-8. The rats were intraperitoneally injected with 1.5 mL of either normal saline (control group), or 3 mg/kg and 6 mg/kg DTX (L-DTX and H-DTX groups, respectively), once a week for 4 weeks. The learning and memory abilities of each group were tested using a water maze. At the end of the water maze test, rats 1-4 in each group were treated with ED (3 mg/kg, 1 mL), and rats 5-8 were injected with an equal volume of normal saline once a day for 2 weeks. The learning and memory abilities of each group were evaluated again using the water maze test, and the image differences in the hippocampus of each group were analyzed using DTI. Results: (1) H-DTX group (32.33 ± 7.83) had the longest escape latency, followed by the L-DTX group (27.49 ± 7.32), and the Control group (24.52 ± 8.11) having the shortest, with the difference being statistically significant (p < 0.05). (2) Following ED treatment, compared to rats treated with normal saline, the escape latency of the L-DTX (12.00 ± 2.79 vs. 10.77 ± 3.97, p < 0.05), and the H-DTX (12.52 ± 3.69 vs. 9.11 ± 2.88, p < 0.05) rats were significantly shortened. The residence time in the target quadrant of H-DTX rats was significantly prolonged (40.49 ± 5.82 vs. 55.25 ± 6.78, p < 0.05). The CNS damage in the L-DTX rats was repaired to a certain extent during the interval between the two water maze tests (28.89 ± 7.92 vs. 12.00 ± 2.79, p < 0.05). (3) The fractional anisotropy (FA) value of DTI in the hippocampus of rats in the different groups showed variable trends. After treatment with ED, though the FA values of most areas in the hippocampus of rats in L-DTX and H-DTX groups were higher than before, they did not reach the normal level. Conclusion: ED can ameliorate the cognitive dysfunctions caused by DTX in rats by improving the learning and memory impairment, which is reflected in the recovery of biological behavior and DTI indicators of the hippocampus.

Efficacy and safety of basal-bolus insulin at 1:1.5 ratio compared to 1:1 ratio using a weight-based initiation and titration (WIT2) algorithm in hospitalized patients with type 2 Diabetes: a multicenter, randomized, clinical study.

BACKGROUND: Most studies initiated basal-bolus insulin in a ratio of 1:1 and titrated based on glucose. This study aimed to investigate the effectiveness and safety of a weight-based and ratio of 1:1.5 basal-bolus insulin using an algorithm for both initiation and titration in hospitalized patients with type 2 diabetes (T2D). METHODS: Hospitalized patients with T2D were randomly assigned to two groups in equal numbers to receive 1:1.5 and 1:1 ratios of basal-bolus insulin using a weight-based algorithm for both initiation and titration. The primary outcome was the time taken to reach the fasting blood glucose (FBG) target and 2-h postprandial blood glucose (2hBG) targets after three meals. The secondary outcome included insulin dosage to achieve glycemic control and the incidence of hypoglycemia during hospitalization. RESULTS: 250 patients were screened between October 2021 and June 2022, 220 were randomly grouped, and 182 completed the trial (89 in the 1:1.5 and 93 in the 1:1 groups). The time taken to reach FBG targets was comparable between the two groups (3.4 ± 1.7 vs. 3.0 ± 1.3 days, p = 0.137) within about 3 days. The 2hBG after three meals was shorter in the 1:1.5 group than in the 1:1group (2.9 ± 1.5 vs. 3.4 ± 1.4 days, p = 0.015 for breakfast, 3.0 ± 1.6 vs. 3.6 ± 1.4 days, p = 0.005 for lunch, and 3.1 ± 2.1 vs. 4.0 ± 1.5 days, p = 0.002 for dinner). No significant difference in insulin dosages was found between the two groups at the end of the study. The incidence of hypoglycemia was similar in both groups. CONCLUSIONS: We demonstrated that fixed dose-ratio basal-bolus insulin at 1:1.5 calculated using a weight-based initiation and titration algorithm was simple, as effective, and safe as ratio at 1:1 in managing T2D in hospitalized patients. Trial Registration ChiCTR 2,100,050,963. Date of registration: September 8, 2021.

Real-World Utilization, Barriers, and Factors Associated With the Targeted Treatment of Metastatic Colorectal Cancer Patients in China: A Multi-Center, Hospital-Based Survey Study.

Objectives: To explore the utilization, barriers, and factors associated with the targeted treatment of Chinese metastatic colorectal cancer (mCRC) patients. Methods: A total of 1,688 mCRC patients from 19 hospitals in 14 cities were enrolled from March 2020 to March 2021 using stratified, multistage cluster sampling. The use of targeted therapy and any barriers patients experienced were collected. Logistic regression analyses were conducted to identify the factors associated with initiating targeted treatment. Results: About 51.6% of the patients initiated targeted therapy, of whom 44.5%, 20.2%, and 35.2% started first-, second-, and third-line treatment, respectively. The most reported barriers were high medical costs and a lack of belief in the efficacy of targeted therapy. Patients treated in the general hospital, diagnosed at an older age, less educated, and who had a lower family income, no medical insurance, poor health-related quality of life, metastasis outside the liver/lung or systemic metastasis, a shorter duration of mCRC were less likely to initiate targeted therapy. Conclusion: Reduced medical costs and interventional education to improve public awareness could facilitate the use of targeted treatment for mCRC.

Texture analysis of myometrium-derived T2WI in the evaluation of placenta increta: An observational retrospective study.

INTRODUCTION: MRI has demonstrated its potential in the diagnosis of placenta percreta. Texture analysis is a novel technique to quantify tissue heterogeneity. The study aimed to evaluate the feasibility of using texture analysis based on myometrium-derived T2WI to differentiate placenta accreta from increta. METHODS: Participants with MRI and clinical or histopathological diagnosis of placenta increta were retrospectively enrolled. Texture analysis of T2WI was implemented on normal myometrium and placenta increta by MaZda software. With the Fisher discriminant method, parameter selection and reduction were done automatically. Multivariate analysis was used for the comparison of response variables between two groups. The contours of multivariable average vectors were compared using profile analysis. Two-step clustering was performed to assess the importance of parameters. RESULTS: There were a total of 23 participants (median age 29 years, range 22-43 years). The pixel intensity distribution was narrow and wide in two first-order histograms taken from normal myometrium and placenta increta, respectively. Multivariate analysis showed nine second-order parameters derived from the histogram were statistically significant (P < 0.05). The results of two-step clustering indicated that three second-order parameters (Mean, Percentile 90%, and Percentile 99%) were important (predictor importance > 0.8). Multivariate analysis of three second-order parameters further showed they were different between normal myometrium and placenta increta. DISCUSSION: Texture analysis based on myometrium-derived T2WI may be a useful add-on to MRI in diagnosing placenta increta. TRIAL REGISTRATION: Registration number: ChiCTR2000038604 and name of registry: Evaluation of diagnostic accuracy of MRI multi-parameter imaging combined with texture analysis for placenta accreta spectrum disorders (PAD).

Application value of multiparametric MRI for evaluating iron deposition in the substantia nigra in Parkinson's disease.

Objective: This study aimed to investigate the application value of multi-parametric magnetic resonance imaging (MRI) in the diagnosis of iron deposition in the substantia nigra dense zone in Parkinson's disease (PD) and to evaluate the diagnostic value of the correlation among multi-parametric imaging indicators, clinical stage, and disease duration. Materials and methods: Thirty-six patients with clinically confirmed PD and 36 healthy controls were enrolled. The disease course was recorded, and PD severity was graded using the Hoehn-Yahr (H-Y) scale. All subjects underwent magnetic sensitivity weighted imaging (SWI), neuromelanin magnetic resonance imaging (NM-MRI), and a T2*mapping sequence. Based on the fusion of the NM-MRI and SWI amplitude maps, phase maps, and T2*MAPPING value maps, NM-MRI was used to delineate the dense zone of the substantia nigra, which was divided into three sub-regions: upper, middle, and lower. In this way, the amplitude, phase, and R2* values of each sub-region and the average value of the sum of the three sub-regions were obtained simultaneously in the SWI amplitude, phase, and T2*MAPPING maps. The multi-parameter imaging indices were compared between the two groups, and the correlation between them and clinical indices was evaluated in the PD group. Results: The upper (amplitude, phase value, R2* value), middle, and lower (amplitude) right substantia nigra compact zones were significantly different between the PD and control groups. The upper (phase value, R2* value) and middle (amplitude) areas of the left substantia nigra compact zone were also significantly different between the two groups (all P < 0.05). The mean values (amplitude, phase value, R2* value) of the right substantia nigra densification zone and the mean values (phase value) of the left substantia nigra densification zone were also significantly different (all P < 0.05). Amplitudes in the middle and lower parts of the right substantia nigra dense zone were negatively correlated with the H-Y grade (middle: r = -0.475, P = 0.003; lower: r = -0.331, P = 0.049). Amplitudes of the middle and lower parts of the dense zone of the left substantia nigra were negatively correlated with the H-Y grade (middle: r = -0.342, P = 0.041; lower: r = -0.399, P = 0.016). The average amplitude of the right substantia nigra compact zone was negatively correlated with the H-Y grade (r = -0.367, P = 0.027). The average R2* value of the compact zone of the left substantia nigra was positively correlated with the H-Y grade (r = 0.345, P = 0.040). Conclusion: Multiparametric MRI sequence examination has application value in the evaluation of iron deposition in the dense zone of the substantia nigra in PD. Combined with NM-MRI, fusion analysis is beneficial for accurately locating the substantia nigra compact zone and quantitatively analyzing the iron deposition in different sub-regions. Quantitative iron deposition in the middle and lower parts of the substantia nigra dense zone may become an imaging biological indicator for early diagnosis, severity evaluation, and follow-up evaluation of PD and is thus conducive for clinical diagnosis and treatment evaluation.