Association between temperature and mortality: a multi-city time series study in Sichuan Basin, southwest China

BACKGROUND@#There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden.@*METHODS@#Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status.@*RESULTS@#A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status.@*CONCLUSIONS@#Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.

Risk Assessment of the Onset of Sleep-related Painful Erection / 中山大学学报(医学科学版)

ObjectiveSleep-related painful erections （SRPE） is a rare sleep disorder characterized by repeated awakening due to painful interruptions of penile erections during nighttime sleep， and its etiology is currently unclear. The purpose of this study is to explore the impact of potential risk factors on the incidence of SRPE. MethodsInformation was collected through questionnaires administered to patients who presented at the urology department and suffered from SRPE or did not suffer from SRPE. A total of 290 participants completed the study， including 145 controls and 145 cases. Logistic regression analysis was used to assess the impact of age， occupation， sleep initiation time per night， frequency of sexual intercourse per week， psychological status， erectile dysfunction， chronic prostatitis， prostate enlargement， lumbar spine disease， central nervous system disease， hypertension， diabetes and family history on the onset of SRPE. ResultsSingle-factor logistic regression analysis found that a history of chronic prostatitis， intellectual labor occupation， central nervous system disease， late sleep onset， frequency of sexual activity， and anxiety status might be related to the onset of SRPE. After incorporating these factors into a multivariate regression analysis model， it was found that having sexual activity ≥2 times/week （OR 95%CI = 0.326（0.179，0.592） and late sleep onset （after 24：00） （OR 95%CI = 0.494（0.265，0.918）might be protective factors for SRPE， while a history of chronic prostatitis（OR 95%CI = 3.779（2.082，6.859） might be a risk factor for SRPE. However， there was no significant statistical difference in the impact of central nervous system diseases and occupation on multivariate analysis. ConclusionChronic prostatitis and anxiety status may be independent risk factors for SRPE； having sexual activity ≥2 times/week and delaying sleep time appropriately may be independent protective factors.

Analysis of cases of reinfection of past SARS-CoV-2 patients in Pudong New Area of Shanghai / 上海预防医学

ObjectiveTo identify the rate， population characteristics， and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai， and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics， nucleic acid or antigen test results， and symptoms after infection. The repeat infection rates among different populations were compared， and logistic regression was used to analyze the impact of gender， age， and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males （53.40%） and 3 528 females （46.60%）， with a median age of 34 years old （P25， P75： 7， 61）. The overall vaccine uptake rate was 59.44% （4 500/7 571）. In December of 2022， there were 563 cases of repeat infection， with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group （2.86%） and the highest rate in the 30‒ year-old group （12.42%）， with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower （6.57%） compared to those who had not （7.11%）. The age groups of 3‒ years， 70‒79 years， as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant， and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots， it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.

Hepatitis C virus infection and organ transplantation / 临床肝胆病杂志

In recent years， rapid progress has been made in strategies for the prevention and treatment of hepatitis C virus （HCV） in organ transplant candidates and recipients， and although HCV infections no longer threaten transplantation outcomes in liver or non-hepatic solid organ transplantation， they remain a focus of research. Since hepatitis C is still a leading cause of death worldwide due to decompensated cirrhosis， liver failure， and hepatocellular carcinoma， appropriate organ transplantation is needed to improve survival rate and quality of life. With the increase in HCV-positive solid organ donors in recent years and the fact that the demand for organs still greatly exceeds organ supply， as well as the development of direct-acting antiviral agents， transplantation of HCV-viraemic organs into HCV-naïve recipients will significantly increase transplantation rates and reduce waitlist mortality. The efficacy of current HCV therapies has created an important opportunity to improve the survival rate of patients with end-organ failure by enhancing access to organ transplantation and reducing waitlist mortality.

Role of SIRTl/Nrf2/HO-l pathway in attenuation of learning and memory impairment by sevoflurane postcondition in a mouse model of hemorrhagic shock and resuscitation / 中国药理学通报

Aim To explore the role of SIRT1/Nrf2 / HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion. Methods C57BL/6J mice were randomly divided into five groups: sham operation group, hemorrhagic shock reperfusion group, sevoflurane postconditioning group, sevoflurane postcondition-ing + SIRT1 inhibitor group and sevoflurane postconditioning + Nrf2 inhibitor group. Mice were subjected to Morris water maze test after cerebral ischemia reperfusion. The ATP, superoxide dismutase (SOD), ROS and MDA contents in tissue of mice were detected. SIRT1, Nrf2 and HO-1 proteins in tissue were detected by Western blot. Results After hemorrhagic shock, the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced , MDA and ROS concentration increased, and the SIRT, Nrf2 and HO-1 concentration was reduced. Sevoflurane improved the cognitive dysfunction and oxi-dative damage in postoperative mice, and the neuro-protective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors. Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/H0-1 pathway.

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Temporal-spatial Generation of Astrocytes in the Developing Diencephalon / 神经科学通报·英文版

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.

Reduced expression of semaphorin 3A in osteoclasts causes lymphatic expansion in a Gorham-Stout disease (GSD) mouse model / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Gorham-Stout disease (GSD) is a sporadic chronic disease characterized by progressive bone dissolution, absorption, and disappearance along with lymphatic vessel infiltration in bone-marrow cavities. Although the osteolytic mechanism of GSD has been widely studied, the cause of lymphatic hyperplasia in GSD is rarely investigated. In this study, by comparing the RNA expression profile of osteoclasts (OCs) with that of OC precursors (OCPs) by RNA sequencing, we identified a new factor, semaphorin 3A (Sema3A), which is an osteoprotective factor involved in the lymphatic expansion of GSD. Compared to OCPs, OCs enhanced the growth, migration, and tube formation of lymphatic endothelial cells (LECs), in which the expression of Sema3A is low compared to that in OCPs. In the presence of recombinant Sema3A, the growth, migration, and tube formation of LECs were inhibited, further confirming the inhibitory effect of Sema3A on LECs in vitro. Using an LEC-induced GSD mouse model, the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo. We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss, whereas the injection of lentivirus expressing Sema3A short hairpin RNA (shRNA) into the tibiae caused GSD-like phenotypes. Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment, compared with the control. Based on the above results, we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

Value of allergen nasal provocation test in assessment of the efficacy of house dust mites specific immunotherapy / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the value of nasal provocation test（NPT） in evaluating the efficacy of allergen immunotherapy（AIT） in patients with dust mite induced allergic rhinitis（AR）. Methods:A total of 83 patients with dust mite induced AR with/without asthma were included. Symptom score（SS）, daily medication score（DMS）, combined symptom and medication score（CSMS）, rhinoconjunctivitis quality of life questionnaire（RQLQ）, NPT and skin prick test（SPT） were assessed before and after 1 year AIT. Results:There were statistical differences in SS（P<0.000 1）, DMS（P<0.000 1）, CSMS（P<0.000 1）, and RQLQ（P<0.000 1） after 1 year of AIT compared with pre-treatment. The effective rate of CSMS was 73.49%, and the effective rate of NPT was 42.17%. CSMS was consistent with NPT in efficacy assessment（Kappa=0.437, P<0.001）; while in 54 patients with pre-treatment NPT concentrations other than the original concentration, CMSM and NPT showed better consistence（Kappa=0.895, P<0.001）. Among the 48 patients with ineffective NPT assessment in the first year, 25 patients completed the second-year follow-up, and 12 patients（48.00%） showed effective in NPT. However, 10 out of 12 patients（83.33%） with NPT concentration other than original solution pre-treatment showed effective NPT at the second year. Conclusion:NPT can be used as one of the indicators for efficacy evaluation for dust mite induced AR patients, especially for patients with positive NPT induced at lower concentrations before treatment.

Neurocircuitry of Predatory Hunting / 神经科学通报·英文版

Predatory hunting is an important type of innate behavior evolutionarily conserved across the animal kingdom. It is typically composed of a set of sequential actions, including prey search, pursuit, attack, and consumption. This behavior is subject to control by the nervous system. Early studies used toads as a model to probe the neuroethology of hunting, which led to the proposal of a sensory-triggered release mechanism for hunting actions. More recent studies have used genetically-trackable zebrafish and rodents and have made breakthrough discoveries in the neuroethology and neurocircuits underlying this behavior. Here, we review the sophisticated neurocircuitry involved in hunting and summarize the detailed mechanism for the circuitry to encode various aspects of hunting neuroethology, including sensory processing, sensorimotor transformation, motivation, and sequential encoding of hunting actions. We also discuss the overlapping brain circuits for hunting and feeding and point out the limitations of current studies. We propose that hunting is an ideal behavioral paradigm in which to study the neuroethology of motivated behaviors, which may shed new light on epidemic disorders, including binge-eating, obesity, and obsessive-compulsive disorders.

Comparison of Effects of Liuzijue Exercise and Conventional Respiratory Training on Patients after Cardiac Surgery: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the feasibility and safety of Liuzijue exercise (LE) for the clinical effect in patients after cardiac surgery.@*METHODS@#Totally 120 patients who underwent cardiac surgery and were admitted to the Cardiothoracic Intensive Care Unit of Nanjing Drum Tower Hospital between July and Oclober, 2022 were allocated to the LE group, the conventional respiratory training (CRT) group, and the control group by a random number table at a ratio of 1:1:1; 40 patients in each group. All patients received routine treatment and cardiac rehabilitation. LE group and CRT group respectively performed LE and CRT once a day for 30 min for 7 days. Control group did not receive specialized respiratory training. The forced vital capacity, forced expiratory volume in 1 s, peak inspiratory flow rate, peak expiratory flow rate, maximum inspiratory pressure, maximum expiratory pressure, modified Barthel index (MBI), and Hamilton Rating Scale for Anxiety (HAM-A) were evaluated before, after 3 and 7 days of intervention. In addition, the postoperative length of hospital stay (LOS) and the adverse events that occurred during the intervention period were compared.@*RESULTS@#A total of 107 patients completed the study, 120 patients were included in the analysis. After 3 days of intervention, the pulmonary function, respiratory muscle strength, MBI and HAM-A of all 3 groups improved compared with that before the intervention (P<0.05 or P<0.01). Compared with the control group, pulmonary function and respiratory muscle strength were significantly improved in the CRT and LE groups (P<0.05 or P<0.01). MBI and HAM-A were significantly improved in the LE group compared with the control and CRT groups (P<0.05 or P<0.01). On the 7th day after intervention, the difference was still statistically significant (P<0.01), and was significantly different from that on the 3rd day (P<0.05 or P<0.01). In addition, on the 7th day of intervention, the pulmonary function and respiratory muscle strength in the LE group were significantly improved compared with those in the CRT group (P<0.01). MBI and HAM-A were significantly improved in the CRT group compared with the control group (P<0.01). There were no significant differences in postoperative LOS among the 3 groups (P>0.05). No training-related adverse events occurred during the intervention period.@*CONCLUSIONS@#LE is safe and feasible for improving pulmonary function, respiratory muscle strength, the ability to complete activities of daily living and for relieving anxiety of patients after cardiac surgery (Registration No. ChiCTR2200062964).

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup / 中国结合医学杂志

OBJECTIVE@#To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients.@*METHODS@#By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup.@*RESULTS@#Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens.@*CONCLUSIONS@#There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Treatment Progress in Diminished Ovarian Reserve: Western and Chinese Medicine / 中国结合医学杂志

Diminished ovarian reserve (DOR), generally defined as a decreased number or quality of oocytes, has a significant impact on quality of life and fertility in women. In recent years, the incidence of DOR has been increasing and the ages of patients are younger. The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health. An effective DOR therapy would improve ovarian function, fertility, and quality of life in patients. In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine, and elucidated the characteristics of each treatment.

Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.@*METHODS@#THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.@*RESULTS@#1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.@*CONCLUSION@#Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

Effect of high-definition transcranial direct current stimulation combined with rehabilitation robot on upper limb and hand function in patients with subacute stroke / 中国康复理论与实践

ObjectiveTo investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) combined with rehabilitation robot on upper limb and hand dysfunction in patients with subacute stroke. MethodsFrom December, 2019 to December, 2021, 50 inpatients with subacute stroke in Zhejiang Provincial People's Hospital were randomly divided into control group (n = 25) and experimental group (n = 25). Both groups received routine rehabilitation therapy, while the control group added sham HD-tDCS combined with rehabilitation robot, and the experimental group added HD-tDCS combined with rehabilitation robot, for four weeks. The upper limb and hand function was assessed with Action Research Arm Test (ARAT), Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and Motor Assessment Scale (MAS) before and after treatment. ResultsAfter treatment, the scores of ARAT, FMA-UE and MAS increased in the two groups (∣Z∣ > 3.320, t > 6.379, P < 0.01), while the scores of FMA-UE and MAS were higher in the experimental group than in the control group (Z = -2.379, t = 3.181, P < 0.05), as well as the scores of grasping and gross motor of ARAT (∣Z∣ > 2.033, P < 0.05). ConclusionThe combination of HD-tDCS and rehabilitation robot can be more effective on upper limb and hand function in patients with subacute stroke than rehabilitation robot alone.

Correlation between intrinsic capacity and activities of daily living for old adults in China: based on China Health and Retirement Longitudinal Study / 中国康复理论与实践

ObjectiveTo explore the weights and comprehensive indices of each field of intrinsic capacity of old adults, and the correlation between intrinsic capacity and activities of daily living (ADL). MethodsThe data of 5 506 cases aged more than 60 years in the 2015 China Health and Retirement Longitudinal Study (CHARLS) were used to collect the assessment of intrinsic capacity and the measurement of ADL. The assessment of intrinsic capacity included cognition, motor, vitality, sensory and psychology; while the ADL scale included six indicators, namely dressing, bathing, eating, getting in or out of bed, going to the toilet, and controlling urine and feces. ResultsA total of 1 343 cases were limited in ADL (24.4%). Women, lower education level, older age, the widowed, greater number of chronic diseases, and poorer self-rated health were the factors more likely to be limited in ADL. Principal component analysis showed that the largest weight value was in psychological domain, followed by the cognitive domain, and the lowest weight value was in the motor domain. After controlling for the effects of age, gender, living environment, economic income, education level, marriage, smoking and drinking, number of chronic diseases, and self-rated health, the Logistic regression analysis showed that low exercise capacity (OR = 0.581, 95%CI 0.501 to 0.674), depression (OR = 0.426, 95%CI 0.368 to 0.493), audile and visual impairment (OR = 0.813, 95%CI 0.699 to 0.947; OR = 0.684, 95%CI 0.578 to 0.809), overweight (OR = 1.203, 95%CI 1.014 to 1.428) and obesity (OR = 1.584, 95%CI 1.312 to 1.912) were independent risk factors for ADL limitation in older adults. ConclusionDecrease of intrinsic capacity is a predictor for ADL limitation in older adults.

SWI/SNF Complex Gene Mutations Promote the Liver Metastasis of Non-small Cell Lung Cancer Cells in NSI Mice / 中国肺癌杂志

BACKGROUND@#The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex.@*METHODS@#The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases.@*RESULTS@#WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group.@*CONCLUSIONS@#This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.

Detection of BCR-ABL Fusion Gene in Chronic Myeloid Leukemia by Novel Digital PCR / 中国实验血液学杂志

OBJECTIVE@#To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230.@*METHODS@#A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared.@*RESULTS@#Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal.@*CONCLUSIONS@#This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome / 生物医学与环境科学（英文）

OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

Research progress on anhepatic phase in rat liver transplantation / 器官移植

With persistent advancement of surgical instruments, methods and techniques, clinical efficacy of liver transplantation has been steadily enhanced. However, the length of anhepatic phase is still an important factor affecting the efficacy of liver transplantation. Rat is one of the major animal models for liver transplantation-related basic research. In this article, multiple approaches for prolonging the anhepatic phase and shortening the operation time during anhepatic phase in rat liver transplantation were reviewed, which consisted of sevoflurane inhalation anesthesia, intravenous infusion via jugular vein indwelling needle, clamping of the abdominal aorta before anhepatic phase, injection of normal saline into portal vein before anhepatic phase, subcutaneous transposition of the spleen, electrocoagulation of hepatic esophageal artery, magnetic ring anastomosis of the superior and inferior hepatic vena cava, cannula anastomosis of the superior and inferior hepatic vena cava, stent anastomosis of the superior and inferior hepatic vena cava, rapid connection device and cannula of portal vein, and ring-shaped cannula of hepatic tissue-preserving inferior hepatic vena cava, aiming to add evidence for prolonging the duration of anhepatic phase, improving the operation efficiency during anhepatic phase and elevating the success rate of rat liver transplantation.