The immediate brain effect of acupuncture at Fengchi in patients with posterior circulation ischemia vertigo:a resting-state functional MRI study / 实用放射学杂志

Objective To investigate the immediate brain effect of acupuncture at Fengchi using amplitude of low-frequency fluctuation(ALFF)and functional connectivity by the resting-state functional magnetic resonance imaging(rs-fMRI)in patients with posterior circulation ischemia vertigo(PCIV).Methods Twenty patients with PCIV were enrolled.The dizziness handicap inventory(DHI)was used to evaluate the severity of vertigo.The patients were randomly divided into acupuncture group and sham acupoint acupuncture group.Rs-fMRI scan was performed before and after acupuncture.MATLAB-based DPABI 6.1 software was used to analyze rs-fMRI data.Correlation analysis was used between the altered ALFF values and DHI scores.The regions of altered ALFF were taken as seeds to analyze functional connectivity.Results Compared with the sham acupoint acupuncture group,the increased ALFF values were mainly located on the left precuneus,left superior frontal gyrus and left caudate nucleus after acupuncture in the acupuncture group;the decreased ALFF values were mainly located on the left cerebellum and right inferior occipital gyrus.The ALFF value of the left superior frontal gyrus was negatively correlated with the DHI score(P=0.04).The increased functional connectivity was mainly found between left precuneus and the right middle frontal gyrus,the right superior frontal gyrus,the decreased functional connectivity was mainly found between left precuneus and the bilateral paracentral lobule and right cerebellum.Conclusion The ALFF value and functional connectivity are different before and after acupuncture,indicating that the vestibular network,visual and motor brain regions functional activities are changed after needling at Fengchi,which may be the brain functional basis of Fengchi for vertigo in PCIV.

Frst-line treatment of Zorifertinib in EGFR-mutant NSCLC with CNS metastases:a report of two cases / 天津医药

Objective To investigate the efficacy of Zorifertinib in first-line treatment of patients with untreated epidermal growth factor receptor(EGFR)mutation in non-small-cell lung cancer(NSCLC)with central nervous system(CNS)metastases.Methods Two patients received Zorifertinib as first-line treatment.The response of tumor treatment was evaluated by response evaluation criteria in solid tumors version 1.1(RECEST v1.1)and RANO criteria for brain metastases(RANO-BM).Results Case 1 had EGFR exon 19del mutation and multiple brain metastases at baseline.After 51.4 months of treatment with Zorifertinib,case 1 still maintained partial response(PR)in lung lesions and complete response(CR)in intracranial lesions.Case 2 had EGFR exon 19del mutation and a single brain metastasis at baseline.Case 2 achieved PR in lung lesions and CR in intracranial lesions during the treatment with Zorifertinib.After 13.7 months,lung disease progression(PD)and new single brain metastases occurred.The comprehensive evaluation was PD.Case 1 had three-grade treatment-related adverse events(TRAEs),including dry skin,and other TRAEs were rash,abnormal liver function and diarrhea.The TRAEs were generally controllable.Conclusion Zorifertinib has a good effect on controlling intracranial and extracranial lesions in patients with EGFR-mutated NSCLC with CNS metastases.The efficacy of Zorifertinib is consistent with the EVEREST study.Zorifertinib can be one of the first-line initial treatment options.

Optimization of preparation method for lung tissue cryosections for multiplex immunofluorescence staining / 中国比较医学杂志

Objective Optimizing the preparation method to improve the quality of mouse lung cryosections to help enhance the specificity of immunofluorescence staining and obtain more accurate and reliable experimental result.Methods C57BL/6 mouse lung tissue was used to make cryosections via the traditional post-freezing fixation method,pre-freezing fixation method,and a modified perfusion pre-freezing fixation method.A laser-scanning confocal microscope was used to observe lung tissue immunofluorescence staining.Whole areas of mouse lung slices were scanned by fluorescence microscope,and the numbers of intact airways per unit area of lung tissue were calculated.Results In the lung cryosections made via the traditional post-freezing fixation method,the alveoli structure was damaged,the airway wall was seriously disrupted,and there was non-specific staining.Lung cryosections made via the pre-freezing fixation method showed relatively intact alveolar and airway structures but collapsed alveoli and several destroyed airways.In the lung cryosections obtained via the modified perfusion pre-freezing fixation method,the structure and morphology of the alveoli and airways were intact and clear.Additionally,the locations of multiple proteins targeted with immunofluorescence staining were accurate.The number of intact airways(diameter ≥100 μm)per unit area in the lung cryosections obtained via the modified perfusion pre-freezing fixation method was higher than that from cryosections made using the pre-freezing fixation method((0.66±0.15)/mm2 vs(0.33±0.14)/mm2,P＜0.05)and was also significantly higher than that from sections made using the traditional post-freezing fixation method((0.66±0.15)/mm2 vs(0.02±0.04)/mm2,P＜0.01).Conclusions The modified perfusion pre-freezing fixation method for cryosections is conducive to maintaining the integrity of mouse lung tissue morphology and obtaining high-quality multiplex immunofluorescence staining result.

Clinical effects of Modified Sanzi Yangqin Decoction combined with acupuncture on patients with chronic obstructive pulmonary disease at stable stage complicated with sarcopenia / 中成药

AIM To explore the clinical effects of Modified Sanzi Yangqin Decoction combined with acupuncture on patients with chronic obstructive pulmonary disease at stable stage complicated with sarcopenia.METHODS Ninety-four patients were randomly assigned into control group(47 cases)for 8-week intervention of conventional treatment,and observation group(47 cases)for 8-week intervention of Modified Sanzi Yangqin Decoction,acupuncture and conventional treatment.The changes in clinical effects,TCM syndrome scores,and levels of pulmonary function indices(FVC,FEV1,FEV1/FVC),inflammatory factors(CRP,IL-6,TNF-α),muscle-specific biomarkers(MSTN,IGF-1),relevant scale scores(SARC-F,SPPB)and skeletal muscle mass index were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,inflammatory factors,MSTN,SARC-F score(P<0.05),and increased pulmonary function indices,IGF-1,SPPB score,skeletal muscle mass index(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with chronic obstructive pulmonary disease at stable stage complicated with sarcopenia,Modified Sanzi Yangqin Decoction combined with acupuncture exhibits significant clinical efficacy.

Effectiveness of Community-Based Rehabilitation (CBR) Centers for Improving Physical Fitness for Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis

To synthesise the best available evidence for the effectiveness of interventions delivered in community-based rehabilitation (CBR) centers on physical fitness, for community-dwelling older adults living in Asian countries. This study is a systematic review and meta-analysis. Seven English and two Chinese electronic databases were searched for randomised controlled trials (RCTs) and quasi-experimental studies that were conducted by centers providing CBR. Independent reviewers screened, quality-appraised and extracted data. The primary outcome was physical fitness measured by validated assessment tools, including the Timed Up and Go Test (TUG), gait speed, hand grip strength, Functional Reach Test (FRT), and one-leg standing test. Assessments of activity of daily living and quality of life using tools including the Barthel Index, Short Form (SF)-12, and SF-36 were secondary outcomes. After screening 5,272 studies, 29 studies were included (16 RCTs, 13 quasi-experimental studies) from four countries. Meta-analyses found that CBR programs significantly decreased TUG time (mean difference [MD], -1.89 seconds; 95% confidence interval [95% CI], -2.84 to -0.94; I2=0%; Z=3.90, p<0.0001), improved gait speed (MD, 0.10 m/s; 95% CI, 0.01–0.18; I2=0%; Z=2.26, p=0.02), and increased one-leg standing time (MD, 2.81 seconds; 95% CI, 0.41–5.22; I2=0%; Z=2.29, p=0.02). Handgrip strength and FRT showed no statistically significant improvement in the meta-analyses. CBR may improve aspects of physical fitness for older adults in Asian countries. However, variability in intervention components and measurement tools reduced the ability to pool individual studies. Further trials are required with robust designs including standardised measures of physical fitness.

Interpretation and reflection on the Measures for the Administration of Standards for Medicinal Products / 中国药房

In July 2023， the National Medical Products Administration issued the Measures for the Administration of Standards for Medicinal Products （hereinafter referred to as the Measures）. This article interprets the main content of the Measures， and analyzes its shortcomings as unclear definition of the drug standard code and the goals of drug standard information construction. It is recommended that the national drug regulatory department promptly apply to the standardization authority for the confirmation of the drug standard code “YB” letter， and the drug standard code and numbering rules would be included in the next round of amendments to the Measures. It is necessary to clarify the construction goals of the information system for drug standards at the same time， and build a national drug standard data-sharing platform based on the basic framework of user interface layer， computing processing layer， and data storage layer. Digital drug standards will be free， and access and download services for the public will be provided.

Landscape changes and livelihood outcomes in rural tea farming communities: A case study in Fuding City, Fujian Province, Southeast China.

Landscape changes driven by cash crop plantations have been prevalent in tropical and subtropical regions worldwide in recent decades. Investigating the landscape changes and concluding livelihood outcomes are fundamental to figure out the solutions for rural sustainability. This paper examined the landscape changes which was caused by land use changes in tea plantations as well as investigated the resultant livelihood impacts, based on a case study in Fuding City, Southeast China. A questionnaire survey of 114 rural households in four sampled villages was conducted. Results demonstrated that expansion and intensification of tea plantations were two major proximate causes of landscape changes in recent decade. Our survey indicated that some existing intensively-managed tea plantations had derived from intensification and expansion of tea plantations, respectively. We identified four underlying driving forces of landscape changes, including economic benefit, governmental policies, wildlife destruction on grain crops, and rural return migration. Our study confirmed that landscape changes have significant positive effects on farmers' livelihoods, including increasing employment and incomes, raising living standards, enhancing livelihood assets and livelihood sustainability. Especially, the aged rural populations could have a relatively decent living standard. Meanwhile, the excessive expansion of tea plantations may impair livelihood resilience. Lastly, three policy suggestions based on different time scales have been put forward to promote rural households' livelihood sustainability and resilience.

Effective personalized neoantigen vaccine plus anti-PD-1 in a PD-1 blockade-resistant lung cancer patient.

Background: Although significant progress has been made in immune checkpoint inhibitor (ICI) treatment of advanced squamous cell carcinoma (SqCC), most patients still experience acquired drug resistance. Methods: We used a dendritic cell-based neoantigen vaccine combined with ICIs to treat advanced SqCC in a PD-1 blockade-resistant patient. Results: The follow-up of this patient after 12 months revealed significant tumor regression. We also identified a new JAK1 ICI-resistant mutation that could become a potential universal neoantigen target for tumor vaccines. Conclusion: Individualized management of advanced SqCC through a combined neoantigen vaccine and ICI administration could yield beneficial clinical outcomes. Vaccines targeting anti-PD-1-resistant JAK1 mutations might be of particular benefit to a specific group of solid tumor patients.

Immunotherapy based on immune checkpoint inhibitors (ICIs) is very effective in lung cancer treatment. However, many patients with initial response will later develop resistance. There are not many treatment options for patients with drug resistance. Herein, we report a patient with lung cancer who became resistant to ICI, treated with personalized vaccine plus ICI. Based on the patient's own somatic mutational profile, personalized neoantigen vaccines were designed and manufactured unique to the patient. Our report indicated that personalized vaccine plus ICI was safe and might overcome ICI resistance. A new ICI resistance mutation on JAK1 as a potential universal neoantigen target for off-the-shelf vaccine was found, which is promising for the effective treatment of a specific group of patients with JAK1 mutations.

Factors associated with poor short-term pharmacotherapy response in self-limited epilepsy with centrotemporal spikes / 中华实用儿科临床杂志

Objective:To explore risk factors for clinical onset in children with uncontrolled self-limited epilepsy with centrotemporal spikes (SeLECTS) managed by 2 anti-seizure medications (ASMs).Methods:A total of 112 children with SeLECTS who were diagnosed at the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University from January 2018 to May 2021 were retrospectively reviewed.All of them were treated with conventional ASMs, and regularly followed up for 1-2 years.Types of therapeutic drugs, clinical seizure control status, presence of new seizure forms, electroencephalogram (EEG) were reviewed at follow-up visits.According to whether the seizures were controlled after the use of no more than 2 ASMs, patients were divided into poor response group (43 cases) and good response group (69 cases), and their clinical data and EEG characteristics were compared.Multivariate Logistic regression analysis was used to explore the risk factors for seizures that were uncontrolled by 2 ASMs. Results:There were significant differences in the age of onset ( χ2=8.919, P=0.003), seizure form ( χ2=4.218, P=0.040), seizure frequency ( Z=-7.664, P<0.001), EEG background slowing ( χ2=10.284, P=0.001), emergence of electrical status epilepticus during slow-wave sleep (ESES)( χ2=11.921, P=0.001), discharge generalization ( χ2=25.377, P<0.001), and presence of epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS)( χ2=54.334, P<0.001) between groups.Multivariate Logistic regression analysis showed that seizure frequency ( P<0.001, OR=0.086, 95% CI: 0.022-0.329), discharge generalization ( P=0.006, OR=9.942, 95% CI: 1.918-51.527) and EEG background slowing ( P=0.041, OR=6.648, 95% CI: 1.077-41.038) were the 3 main risk factors associated with poor response to short-term medications of ASMs. Conclusions:Seizures are easily controlled in most SeLECTS patients medicated with ASMs with a favorable prognosis.Seizure frequency, discharge generalization and EEG background slowing are risk factors for the poor response to short-term pharmacotherapy in children with SeLECTS.

Exploration and thinking of standardized residency training education for the residents in the intensive care unit of neurosurgery department / 中华医学教育探索杂志

Critical neurosurgery is one of the difficulties and key points in the standardized residency training of neurosurgery. Through the systematic and standardized training of the residents of the Intensive Care Unit of Neurosurgery Department in The First Affiliated Hospital of Chongqing Medical University, consisting of first aid skills training, multi-modal case analysis with complementary theory and practice, expansion of neuroimaging and electrophysiological knowledge, specialized knowledge training in surgical operation and perioperative management, and regular case discussion, their clinical thinking becomes more mature, the time to master the management methods of neurosurgical intensive care patients is significantly shortened, the initiative to participate in clinical practice is also significantly increased, and the perioperative management methods of neurosurgical patients are more deeply understood. These trainings have effectively improved the teaching effect of neurosurgery intensive care unit.

Application of outcome-based education combined with team-based learning in practice teaching of pediatric emergency and critical care nursing / 中华医学教育探索杂志

Objective:To investigate the application value of outcome-based education (OBE) combined with team-based learning (TBL) in the practice teaching of pediatric emergency and critical care nursing.Methods:A total of 84 nursing students who studied in the pediatric intensive care unit (PICU) of The First Affiliated Hospital of Air Force Medical University were selected and divided into control group and observation group. The 41 nursing students in the control group received traditional teaching, and the 43 nursing students in the observation group received OBE+TBL teaching. The two groups were assessed in terms of theoretical knowledge, practical operation ability, clinical thinking ability, and self-learning ability after teaching, and the degrees of satisfaction with teaching and participation in teaching were compared between the two groups. SPSS 22.0 was used for the t-test and the chi-square test. Results:After teaching, the observation group had significantly better theoretical knowledge, practical operation ability, and self-learning ability than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher scores of learning engagement (recognition, behavior, emotion) ( P<0.05) and satisfaction with classroom effect, knowledge mastery, and learning interest ( P<0.05). Conclusion:The application of OBE+TBL teaching in PICU nursing students can effectively improve their self-learning ability and participation and help them to understand PICU nursing priorities and improve their practical operation ability.

Application of ultrasonic shear wave elastography to the assessment of skin lesion in patients with systemic sclerosis / 中华风湿病学杂志

Objective:To evaluate the value of shear wave elastography (SWE) in skin assessment of Systemic sclerosis (SSc).Methods:A total of 58 SSc patients admitted to Peking University Third Hospital from May 2021 to October 2022 and 41 healthy volunteers were included in the study. Skin shear wave elastography (SWE) was performed at 17 sites defined in modified Rodnan skin score (mRSS) measurement, and shear wave velocity values were recorded to evaluate skin hardness. SPSS 22.0 software was used to analyze the skin hardness of SSc patients and healthy controls, and the correlation between skin hardness of SSc patients and clinical data was analyzed. A logistic regression model was constructed to evaluate the diagnostic efficacy of skin hardness at different sites of SSc patients, and to further select the most practical measurement site.Results:The SWE value of SSc patients was significantly higher than that of healthy control group ( P<0.05). There was a positive correlation between SWE and mRSS in the measurement of bilateral fingers, bilateral dorsal hands, bilateral forearms, fore-chest, abdomen, bilateral thighs, and bilateral dorsal feet. Skin stiffness measured by SWE was significantly correlated with SSc disease activity score (EScSG-DAI), ( r=0.71, P<0.001), disease injury score (SCTC-DI), (P=0.55, P=0.005) and functional score (HAQ-DI), ( r=0.46, P=0.003). Reducing the number of measurement sites to 12 (bilateral fingers, bilateral hands, bilateral forearms, bilateral upper arms, forehead, fore-chest, bilateral dorsum of feet) performs as well as all 17 measurement sites simultaneously in assessing disease activity. Conclusion:SWE is a good evaluation tool to reflect the skin lesions of SSc, which is of great value for the diagnosis and evaluation of the disease. We can further standardize the measurement sites and select the most appropriate evaluation strategy, so as to achieve better clinical application.

Quantitative analysis of myocardial fibrosis in dilated cardiomyopathy with deep learning joint segmentation model / 中华放射学杂志

Objective:To explore the effect of joint segmentation model of myocardial-fibrotic region based on deep learning in quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy(DCM).Methods:The data of 200 patients with confirmed DCM and myocardial fibrosis in the left ventricle detected by cardiac MR-late gadolinium enhancement (CMR-LGE) in Xuzhou Central Hospital from January 2015 to April 2022 were retrospectively analyzed. Using a complete randomized design, the patients were divided into training set ( n=120), validation set ( n=30) and test set ( n=50). The left ventricle myocardium was outlined and the normal myocardial region was selected by radiologists. Fibrotic myocardium was extracted through calculating the threshold with standard deviation (SD) as a reference standard for left ventricle segmentation and fibrosis quantification. The left ventricular myocardium was segmented by convex prior U-Net network. Then the normal myocardial image block was recognized by VGG image classification network, and the fibrosis myocardium was extracted by SD threshold. The myocardial segmentation effect was evaluated using precision, recall, intersection over union (IOU) and Dice coefficient. The consistency of myocardial fibrosis ratio in left ventricle obtained by joint segmentation model and manual extraction was evaluated with intra-class correlation coefficient (ICC). According to the median of fibrosis rate, the samples were divided into mild and severe fibrosis, and the quantitative effect of fibrosis was compared by Mann-Whitney U test. Results:In the test set, the precision of myocardial segmentation was 0.827 (0.799, 0.854), the recall was 0.849 (0.822, 0.876), the IOU was 0.788 (0.760, 0.816), and the Dice coefficient was 0.832 (0.807, 0.857). The consistency of fibrosis ratio between joint segmentation model and manual extraction was high (ICC=0.991, P<0.001). No statistically significant difference was found in the ratio error between mild and severe fibrosis ( P>0.05). Conclusions:The joint segmentation model realizes the automatic calculation of myocardial fibrosis ratio in left ventricle, which is highly consistent with the results of manual extraction. Therefore, it can accurately realize the automatic quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy.

Treatment of Critical COVID-19 Case Complicated with Multiple Organ Dysfunction based on “Cold-dampness Entering Ying （营）” Theory： A Case Report / 中医杂志

“Cold-dampness entering ying （营）” is the key to the worsening of cold-dampness epidemic， and is more common in the elderly or critically ill cases of cold-dampness epidemic with pathogen exuberance and healthy qi deficiency. This paper reported a case of critically ill COVID-19 combined with multiple organ dysfunction treated by integrative traditional Chinese and western medicine based on “cold-dampness entering ying” theory. The patient did not have high fever after being infected with SARS-Cov-2， but D-dimer continued to increase， and she developed multiple thrombosis throughout the body and multiple organ dysfunctions such as pulmonary embolism， edema， oliguria， and shock. The patient were with enlarged and dusky tongue， with yellow， thick and greasy coating， and sublingual blood stasis， and thready， rapid and rough pulse. All these were characteristic manifestations of “cold-dampness entering ying”， and was differentiated as cold-dampness stasis. For the treatment， symptomatic and supportive western medicine of improving heart function， anti-infection， relieving asthma， stopping cough and reducing phlegm was given as the basic therapy， and additionally， traditional Chinese medicine to open the constraint and the blocked， save from collapse and restore yang， boost qi and relieve collapse， invigorate blood and drain water was used， usually with Modified Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤加减）， which was in accordance with the pathogenesis and thus achieving good effect.

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Diagnostic value of contrast-enhanced ultrasound in hepatic epithelioid hemangioendothelioma / 中华肝脏病杂志

Objective: To investigate the features of contrast-enhanced ultrasound (CEUS) in hepatic epithelioid hemangioendothelioma (HEHE) in order to improve the preoperative diagnosis rate. Methods: CEUS images of 32 pathologically-proven cases of hepatic epithelioid hemangioendothelioma from January 2004 to August 2021 were collected. Lesions were analyzed to observe the features of enhancement mode, enhancement intensity, and distinct enhancement phases. Results: Among the 32 cases, one had a solitary lesion, 29 had multiple lesions, and two had diffuse-type lesions. Contrast-enhanced ultrasound revealed a total of 42 lesions in 32 cases. In terms of arterial phase enhancement, 18 lesions had overall enhancement, six lesions had uneven dendritic enhancement, 16 lesions had rim-like enhancement, and two lesions had just slight peripheral spot enhancement around the lesions. Among the three cases, there were multiple lesions that had overall enhancement and ring enhancement. In terms of the enhancement phase, 20 lesions showed "fast progression", 20 lesions showed "same progression", and two lesions showed "slow progression". During the late arterial or early portal venous phases with rapid washout, all lesions manifested as hypoechoic. With peaked enhanced intensity, 11 lesions had a lower enhancement intensity than the surrounding normal liver parenchyma; 11 lesions had the same enhancement degree as the surrounding normal liver parenchyma; and 20 lesions had a higher enhancement degree than the surrounding normal liver parenchyma. All 16 ring-enhancing lesions had marked hyperenhancement. In the typical enhancing lesions, four showed hyperenhancement, five showed low enhancement, and nine showed isoenhancement. In the dendrite-enhancing lesions, there were two isoenhancing and four hypoenhancing. Contrast-enhanced ultrasound delineated the boundaries of all lesions more clearly than two-dimensional ultrasound. Conclusion: Contrast-enhanced ultrasound has certain value in the diagnosis of hepatic epithelioid hemangioendothelioma.

Progress in Development of Targeted Therapeutic Drugs for Acute Myeloid Leukemia / 肿瘤防治研究

Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.

WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice / 神经科学通报·英文版

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.

Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity / 药物分析学报

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hip-pocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Func-tionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.