Epidemiologic characteristics of oral cancer:single-center analysis of 4097 patients from the Sun Yat-sen University Cancer Center

Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic characteristics of oral cancer in South China.Methods:We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013.We compared the age of onset,sex ratio,pathologic type,and primary tumor location among three subcultural areas(Guangfu,Hakka,and Chaoshan) and between an economically developed region and a less-developed one in Guangdong.Results:Overall,oral cancer had a male-to-female ratio of approximately 2:1,and this ratio decreased over time.Oral cancer occurred mostly in patients of 45-64 years old(54.5%),and the percentage of older patients gradually increased over time.The most common tumor location was the tongue.Squamous cell carcinoma was the predominant pathologic type.The percentage of blood type O in oral cancer patients was lower than that in the healthy population.The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas,whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan.The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region.Conclusion:The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.

Forty-six cases of nasopharyngeal carcinoma treated with 50 Gy radiotherapy plus hematoporphyrin derivative:20 years of follow-up and outcomes from the Sun Yat-sen University Cancer Center

Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dose radio?therapy can improve the Qo L without affecting clinical efficacy is unknown.This study aimed to assess the survival rates and Qo L of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative(HPD).Methods:Forty?six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed.All patients were restaged according to the 7th edition of the American Joint Commit?tee on Cancer staging system.The radiotherapy plan was designed on the basis of pretreatment computed tomog?raphy.The OS,local recurrence?free survival(LRFS),distant metastasis?free survival(DMFS),and disease?free survival(DFS) rates were estimated using the Kaplan–Meier method.Qo L was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group.Results:The 5?year OS,LRFS,DMFS,and DFS rates were 74.3%,72.6%,82.1%,and 61.2%,respectively.The corre?sponding 10?year rates were 38.4%,62.9%,78.5%,and 49.8%,respectively,and the 20?year rates were 27.7%,51.4%,78.5%,and 40.7%,respectively.None of the patients developed severe radiation?related complications,such as radiation?induced temporal lobe necrosis,hearing loss,trismus,and dysphagia.Conclusion:Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD,and this sensitivity was characterized by long?term survival without significant late treatment morbidities.

A Study on‘the Market for Lemons’and the Strategy of‘Unification’in Booking Systems:A Case Study on the FAHSYSU Simulation T System of the Training Center for Clinical Skills of the First Affiliated Hospital of Sun Yat-sen University

Based on the blueprint of the training center for clinical skills of our hospital,this paper discusses the effect of‘the market for lemons’in its booking system from the perspective of economics of information,uses the law of large numbers and the central limit theorem to model to carry out the case study of FAHSYSU Simulation T,and takes measures of offsetting adverse selections to increase booking efficiency.The paper also analyzes how to apply the ancient Chinese theory that man is an integral part of nature to wipe out‘the market for lemons’.

Translational oncology toward benefiting cancer patients:the Sun Yat-sen University Cancer Center experience

Cancer is a leading cause of death in China with an estimation of nearly 2 million deaths every year(Chen and Fu,2011b).Matter of a public health importance in China and worldwide,the scientific community is still facing

Posttraumatic stress symptom trajectories of Chinese university students during the first eight months of the COVID-19 pandemic and their association with cognitive reappraisal,expressive suppression,and posttraumatic growth

Objective: To identify the moderating effects of cognitive reappraisal(CR) and expressive suppression(ES) on the relationship between posttraumatic stress(PTS) symptoms and posttraumatic growth(PTG) in university students. Methods: The survey included 1 987 Chinese university students who completed questionnaires on PTS symptoms in February 2020, with three follow-up surveys at two-month intervals until August 2020. We assessed CR and ES at February 2020 and PTG at August 2020. Growth mixture modeling was used to classify the PTS symptom trajectories. Multinomial logistic regression was used to recognize the predictors of class membership. The relationships among PTS symptoms, CR, ES, and PTG were examined using multi-group path analysis.Results: Sex, SARS-Co V-2 infection of a family member or friend, number of siblings, CR, and ES were significantly associated with PTS symptoms. Three latent classes were identified: ‘Increasing PTS’(n=205, 10.0%) who had rapid deterioration of PTS symptoms, ‘Moderate PTS’(n=149, 8.0%) who had a high level of PTS symptoms at the beginning and slightly increasing, and ‘Persistent Minimal PTS’(n=1 633, 82.0%), who had slow resolution of PTS symptoms over time. Male, SARS-Co V-2 infection of a family member or friend, and having a lower CR and a higher ES, were more likely to have ‘Increasing PTS’. PTS at February 2020 predicted PTG only in ‘Increasing PTS’ class, and both CR and ES had moderating effects on the conversion between them.Conclusions: Most students recovered from posttraumatic stress of COVID-19 pandemic, but a small proportion expeienced increasing PTS symptoms, and those with this condition may benefit from emotional regulation intervention.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.

Differences in spring precipitation over southern China associated with multiyear La Ni?a events

Composite analyses were performed in this study to reveal the difference in spring precipitation over southern China during multiyear La Ni?a events during 1901 to 2015. It was found that there is significantly below-normal precipitation during the first boreal spring, but above-normal precipitation during the second year. The difference in spring precipitation over southern China is correlative to the variation in western North Pacific anomalous cyclone(WNPC), which can in turn be attributed to the different sea surface temperature anomaly(SSTA) over the Tropical Pacific. The remote forcing of negative SSTA in the equatorial central and eastern Pacific and the local air-sea interaction in the western North Pacific are the usual causes of WNPC formation and maintenance.SSTA in the first spring is stronger than those in the second spring. As a result, the intensity of WNPC in the first year is stronger, which is more likely to reduce the moisture in southern China by changing the moisture transport, leading to prolonged precipitation deficits over southern China. However, the tropical SSTA signals in the second year are too weak to induce the formation and maintenance of WNPC and the below-normal precipitation over southern China. Thus, the variation in tropical SSTA signals between two consecutive springs during multiyear La Ni?a events leads to obvious differences in the spatial pattern of precipitation anomaly in southern China by causing the different WNPC response.

Natural sources,refined extraction,biosynthesis,metabolism,and bioactivities of dietary polymethoxyflavones(PMFs)

Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.

Research on Pulsar Time Steered Atomic Time Algorithm Based on DPLL

In today’s society,there is a wide demand for high-precision and high-stability time service in the fields of electric power,communication,transportation and finance.At present,the time standard in various countries is mainly based on atomic clocks,but the frequency drift of atomic clocks will affect the long-term stability performance.Compared with atomic clocks,millisecond pulsars have better long-term stability and can complement with the excellent short-term stability of atomic clocks.In order to improve the long-term stability of the atomic timescale,and then improve the timing accuracy,this paper proposes an algorithm for steering the atomic clock ensemble(ACE)by ensemble pulsar time(EPT)based on digital phase locked loop(DPLL).First,the ACE and EPT are generated by the ALGOS algorithm,then the ACE is steered by EPT based on DPLL to calibrate the long-term frequency drift of the atomic clock,so that the generated steered atomic time follows both the short-term stability characteristics of ACE and the long-term stability characteristics of EPT,and finally,the steered atomic time is used to calibrate the local cesium clock.The experimental results show that the long-term stability of atomic time after steering is improved by 2 orders of magnitude compared with that before steering,and the daily drift of a local cesium clock after calibration is less than 9.47 ns in 3 yr,3 orders of magnitude higher than that before calibration on accuracy.

Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Microarrow sensor array with enhanced skin adhesion for transdermal continuous monitoring of glucose and reactive oxygen species

Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.

A Rendezvous Mission to the Second Earth Trojan Asteroid 2020 XL_5 with Low-Thrust Multi-Gravity Assist Techniques

As the second of Earth's Trojan asteroids, 2020 XL_(5) is worthy of rendezvous and even sample return missions in many aspects. In this paper, a rendezvous mission to Earth's second Trojan asteroid 2020 XL_(5) is proposed.However, due to its high inclination and large eccentricity, direct impulsive transfer requires large amounts of fuel consumption. To address this challenge, we explore the benefits of electric propulsion and multi-gravity assist techniques for interplanetary missions. These two techniques are integrated in this mission design. The design of a low-thrust gravity-assist(LTGA) trajectory in multi-body dynamics is thoroughly investigated,which is a complex process. A comprehensive framework including three steps is presented here for optimization of LTGA trajectories in multi-body dynamics. The rendezvous mission to 2020 XL_(5) is designed with this three-step approach. The most effective transfer sequence among the outcomes involves Earth–Venus–Earth–Venus-2020 XL_(5). Numerical results indicate that the combination of electric propulsion and multi-gravity assists can greatly reduce the fuel consumption, with fuel consumption of 9.03%, making it a highly favorable choice for this rendezvous mission.

An improved algorithm for retrieving thin sea ice thickness in the Arctic Ocean from SMOS and SMAP L-band radiometer data

The aim of this study was to develop an improved thin sea ice thickness(SIT)retrieval algorithm in the Arctic Ocean from the Soil Moisture Ocean Salinity and Soil Moisture Active Passive L-band radiometer data.This SIT retrieval algorithm was trained using the simulated SIT from the cumulative freezing degree days model during the freeze-up period over five carefully selected regions in the Beaufort,Chukchi,East Siberian,Laptev and Kara seas and utilized the microwave polarization ratio(PR)at incidence angle of 40°.The improvements of the proposed retrieval algorithm include the correction for the sea ice concentration impact,reliable reference SIT data over different representative regions of the Arctic Ocean and the utilization of microwave polarization ratio that is independent of ice temperature.The relationship between the SIT and PR was found to be almost stable across the five selected regions.The SIT retrievals were then compared to other two existing algorithms(i.e.,UH_SIT from the University of Hamburg and UB_SIT from the University of Bremen)and validated against independent SIT data obtained from moored upward looking sonars(ULS)and airborne electromagnetic(EM)induction sensors.The results suggest that the proposed algorithm could achieve comparable accuracies to UH_SIT and UB_SIT with root mean square error(RMSE)being about 0.20 m when validating using ULS SIT data and outperformed the UH_SIT and UB_SIT with RMSE being about 0.21 m when validatng using EM SIT data.The proposed algorithm can be used for thin sea ice thickness(<1.0 m)estimation in the Arctic Ocean and requires less auxiliary data in the SIT retrieval procedure which makes its implementation more practical.

Lipase and photodecarboxylase coexpression: A potential strategy for alkane-based biodiesel production from natural triglycerides

Alkane-based biodiesel is considered the next generation of biodiesel owing to its potential environmental benefits and the fact that it exhibits much higher specific caloric values than traditional biodiesel.However,the formidable obstacle impeding the commercialization of this cutting-edge fuel alternative lies in the cost associated with its production.In this study,an engineered strain Escherichia coli(E.coli)showcasing harmonized coexpression of a lipase(from Thermomyces lanuginosus lipase,TLL)and a fatty acid photodecarboxylase(from Chlorella variabilis,CvFAP)was first constructed to transform triglycerides into alkanes.The potential of E.coli BL21(DE3)/pRSFDuet-1-TLL-CvFAP for alkane synthesis was evaluated with tripalmitin as a model substrate under various process conditions.Following a comprehensive examination of the reaction parameters,the scope of the biotransformation was expanded to‘real’substrates(vegetable oils).The results showed that bioderived oils can be transformed into alkanes with high yields(0.80-10.20 mmol·L^(-1))under mild conditions(35℃,pH 8.0,and 36 h)and blue light illumination.The selected processes were performed on an increased lab scale(up to 100 ml)with up to 24.77 mmol·L^(-1) tripalmitin,leading to a yield of 18.89 mmol·L^(-1) pentadecane.With the employment of a method for efficiently producing alkanes under mild conditions and a simple procedure to isolate alkanes from the reaction system,the utilization of sustainable biomass as a fundamental feedstock emerges as the primary solution to lower the cost of alkane-based biodiesel.Thus,this study proposes a readily implementable and highly effective approach for alkane-based biodiesel production.

Semi-implantable device based on multiplexed microfilament electrode cluster for continuous monitoring of physiological ions

Modern medicine is increasingly interested in advanced sensors to detect and analyze biochemical indicators.Ion sensors based on potentiometric methods are a promising platform for monitoring physiological ions in biological subjects.Current semi-implantable devices are mainly based on single-parameter detection.Miniaturized semi-implantable electrodes for multiparameter sensing have more restrictions on the electrode size due to biocompatibility considerations,but reducing the electrode surface area could potentially limit electrode sensitivity.This study developed a semi-implantable device system comprising a multiplexed microfilament electrode cluster(MMEC)and a printed circuit board for real-time monitoring of intra-tissue K^(+),Ca^(2+),and Na^(+)concentrations.The electrode surface area was less important for the potentiometric sensing mechanism,suggesting the feasibility of using a tiny fiber-like electrode for potentiometric sensing.The MMEC device exhibited a broad linear response(K^(+):2–32 mmol/L;Ca^(2+):0.5–4 mmol/L;Na^(+):10–160 mmol/L),high sensitivity(about 20–45 mV/decade),temporal stability(>2weeks),and good selectivity(>80%)for the above ions.In vitro detection and in vivo subcutaneous and brain experiment results showed that the MMEC system exhibits good multi-ion monitoring performance in several complex environments.This work provides a platform for the continuous real-time monitoring of ion fluctuations in different situations and has implications for developing smart sensors to monitor human health.

Early proactive monitoring of DNA-thioguanine in patients with Crohn’s disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers

BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Risk factors of non-arteritic anterior ischaemic optic neuropathy and central retinal artery occlusion

AIM:To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy(NAION)and central retinal artery occlusion(CRAO)and develop a predictive diagnostic nomogram.METHODS:The study included 37 patients with monocular NAION,20 with monocular CRAO,and 24 with hypertension.Gender,age,and systemic diseases were recorded.Blood routine,lipids,hemorheology,carotid and brachial artery doppler ultrasound,and echocardiography were collected.The optic disc area,cup area,and cup-to-disc ratio(C/D)of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured.RESULTS:The carotid artery intimal medial thickness(C-IMT)of the affected side of the CRAO group was thicker(P=0.039)and its flow-mediated dilation(FMD)was lower(P=0.049)than the NAION group.Compared with hypertension patients,NAION patients had higher whole blood reduced viscosity low-shear(WBRV-L)and erythrocyte aggregation index(EAI;P=0.045,0.037),and CRAO patients had higher index of rigidity of erythrocyte(IR)and erythrocyte deformation index(EDI;P=0.004,0.001).The optic cup and the C/D of the NAION group were smaller than the other two groups(P<0.0001).The diagnostic prediction model showed high diagnostic specificity(83.7%)and sensitivity(85.6%),which was highly related to hypertension,the C-IMT of the affected side,FMD,platelet(PLT),EAI,and C/D.CONCLUSION:CRAO patients show thicker C-IMT and worse endothelial function than NAION.NAION and CRAO may be related to abnormal hemorheology.A small cup and small C/D may be involved in NAION.The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.