Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions

AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and controls.In the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.Using lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in vivo.High glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in vitro.The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,respectively.RESULTS:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq approach.Besides,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection.Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction levels.In vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation.Down-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in vitro.CONCLUSION:The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions.Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage,reduce vascular leakage,cell apoptosis,and maintain vascular endothelial cell barrier function.

Rehabilitation care for pain in elderly knee replacement patients

BACKGROUND Total knee arthroplasty(TKA)is recognized as the most effective surgical intervention for relieving pain and improving joint mobility and deformity in patients with knee osteoarthritis and other synovial diseases.The application of accelerated postoperative rehabilitation(enhanced recovery after surgery)has demonstrated its efficacy in improving patient outcomes,and early postoperative joint function exercise has become a key prognostic factor in knee replacement.The unexpected appearance of limb pain and swelling hindered the patient’s tendency for early mobilization,leading in prolonged hospitalization,delayed functional recovery and negative psychological responses.A retrospective analysis was conducted on a cohort of 116 patients who under-went TKA at our hospital between July 2019 and July 2021.The patients were divided into two groups:A control group(n=58)receiving programmatic nur-sing,and an observed group(n=58)receiving programmed nursing combined with a collaborative nursing model.A pain management team consisting of attending physicians,head nurses,and responsible nurses was established.Outcome measures included visual analogue scale(VAS)scores,activities of daily living(ADL)scale scores,and functional scores.The ADL scores of patients in both groups exhibited a continuous increase.However,there was no statistically significant difference in the ADL scores between the two groups at 48 h and the 7th d post-surgery(P>0.05).Upon reexamination at the 3rd mo,the observation group demonstrated higher ADL scores compared to the control group(67.48±14.69 vs 59.40±16.06,P<0.05).The VAS scores of both groups significantly decreased,with no significant difference observed between the groups at each time point(P>0.05).The functional status of patients in both groups exhibited a gradual increase prior to intervention and at the 1st,2nd,and 3rd month following discharge(P<0.05).There was no statistically significant difference in knee joint function scores between the two groups at the 1st month after discharge(47.52 vs 45.81,P>0.05).However,the knee joint function scores of patients in the observation group were significantly higher than those in the control group at the 2nd(59.38 vs 53.19,P<0.05)and 3rd month(71.92 vs 64.34,P<0.05)following discharge.CONCLUSION The utilization of programmed pain nursing in conjunction with collaborative nursing for out-of-hospital care of TKA patients has demonstrated favorable outcomes,encompassing pain reduction,enhanced prognosis,and improved nursing quality for patients.

基于水系沉积物地球化学采样的地形加权图卷积网络基岩填图方法

为了探索高效的第四系覆盖及露头较少区域的基岩智能填图方法,应用图卷积网络(GCN)对青海省察汗乌苏河地区水系沉积物地球化学采样的下伏基岩进行分类。基于Delaunay三角化采样点被组织为一个地形加权的有向图来表达水系沉积物地球化学采样点之间的河流上下游关系。实验结果表明:半监督的GCN模型仅使用了20%的采样点标签,分类精度达到68.20%(10类基岩)和78.31%(5类基岩)。该方法能有效利用水系沉积物地球化学采样中的元素含量进行基岩填图,且能提高基岩填图的效率并能进行大面积应用。

Clinical study of acupuncture combined with surface anesthesia using proparacaine in geriatric cataract phacoemulsification

BACKGROUND During anesthesia administration for cataract surgery,low pH of proparacaine may induce pain or complications such as corneal damage and poor wound healing,with the use of additional drops intraoperatively increasing the risk of complications.Accordingly,there is a clinical need for adjuncts to local anesthesia needs to improve the efficiency of anesthesia and reduce the required amount of intraoperative proparacaine.AIM To identify a method of anesthesia for geriatric cataract phacoemulsification that provides more efficient analgesia and improves clinical efficacy.METHODS A total of 130 geriatric patients with cataracts who attended Hebei Eye Hospital from December 2020 to December 2022 were included in the present study.Patients were divided into the proparacaine surface anesthesia(SA)group(65 cases)and the compound acupuncture-medicine anesthesia group(CAMA group,65 cases).Patients in the CAMA group were provided acupuncture analgesia in addition to SA.Preoperative anxiety[Self-Rating Anxiety Scale(SAS)score and state anxiety inventory(SAI)score],intraoperative stress,vital signs,analgesia,and cooperation,as well as postoperative adverse events,were compared between groups.RESULTS More marked reductions in anxiety were observed among patients in the CAMA group,with corresponding reductions in SAS and SAI scores.During the operation,no change in the secretion of E,NE,or Cor group compared to the preoperative period was observed in the CAMA,which was markedly lower than that in the SA group.Heart rate,blood pressure,and respiratory rate were more stable intraoperatively in the CAMA group.In addition,the incidence of intraoperative pain and the number of additional doses of anesthesia required in the CAMA group were markedly lower than in the SA group.Accordingly,patients in the CAMA group were able to avoid eye movements and eyelid closing leading to greater cooperation with surgeons during surgery.Furthermore,marked reductions in intraoperative adverse effects were observed in the CAMA group,indicating greater overall safety.CONCLUSION Proparacaine SA combined with acupuncture as an analgesic provides improved analgesia with greater safety compared to surface anesthesia with proparacaine during geriatric cataract phacoemulsification.

Rapid Detection of rpoB Gene Mutations in Rif-resistant M.tuberculosis Isolates by Oligonucleotide Microarray

Objective To detect the specific mutations in rpoB gene of Mycobacterium tuberculosis by oligonucleotide microarray. Methods Four wild-type and 8 mutant probes were used to detect rifampin resistant strains. Target DNA of M. tuberculosis was amplified by PCR, hybridized and scanned. Direct sequencing was performed to verify the results of oligonucleotide microarray Results Of the 102 rifampin-resistant strains 98 （96.1%） had mutations in the rpoB genes. Conclusion Oligonucleotide microarray with mutation-specific probes is a reliable and useful tool for the rapid and accurate diagnosis of rifampin resistance in M. tuberculosis isolates.

Comprehensive evaluation on the ecological function of groundwater in the Shiyang River watershed

With an arid climate and shortage of water resources,the groundwater dependent ecosystems in the oasis-desert ecotone of the Shiyang River Watershed has been extremely damaged,and the water crisis in the oasis has become a major concern in the social and the scientific community.In this study,the degene-ration characteristics of the groundwater ecological function was identified and comprehensive evaluated,based on groundwater depth data,vegetation quadrat and normalized difference vegetation index(NDVI)from Landsat program.The results showed that(1)the suitable groundwater depth for sustainable ecology in the Shiyang River Watershed is about 2-4 m;(2)the terms of degenerative,qualitative and disastrous stages of the groundwater ecological function are defined with the groundwater depths of about 5 m,7 m and 10 m;(3)generally,the groundwater ecological function in the oasis-desert ecotone of the lower reaches of Shiyang River Watershed is weak with an area of 1397.9 km2 identified as the severe deterioration region,which accounted 74.7%of the total area.In the meantime,the percentages of the good,mild and moderate deterioration areas of groundwater ecological function are 3.5%,5.5%and 16.3%,respectively,which were mainly distributed in the Qingtu lake area and the southeastern area of the Shoucheng town;(4)the degradation and shrinkage of natural oasis could be attributed to the dramatic groundwater decline,which is generally caused by irrational use of water and soil resources.This study could provide theoretical basis and scientific support for the decision-making in environmental management and ecological restoration of the Shiyang River Watershed.

The influence of He-Ne laser on scar formation after trabeculectomy in rabbits

AIMTo investigate the influence of He-Ne lasers on scar formation in the filtration canal after trabeculectomy in a rabbit model, as well as to explore the mechanisms for preventing scar formation when using He-Ne lasers in vivo.

Influence of helium on the evolution of irradiation-induced defects in tungsten:An object kinetic Monte Carlo simulation

Understanding the evolution of irradiation-induced defects is of critical importance for the performance estimation of nuclear materials under irradiation.Hereby,we systematically investigate the influence of He on the evolution of Frenkel pairs and collision cascades in tungsten(W)via using the object kinetic Monte Carlo(OKMC)method.Our findings suggest that the presence of He has significant effect on the evolution of irradiation-induced defects.On the one hand,the presence of He can facilitate the recombination of vacancies and self-interstitial atoms(SIAs)in W.This can be attributed to the formation of immobile He-SIA complexes,which increases the annihilation probability of vacancies and SIAs.On the other hand,due to the high stability and low mobility of He-vacancy complexes,the growth of large vacancy clusters in W is kinetically suppressed by He addition.Specially,in comparison with the injection of collision cascades and He in sequential way at 1223 K,the average sizes of surviving vacancy clusters in W via simultaneous way are smaller,which is in good agreement with previous experimental observations.These results advocate that the impurity with low concentration has significant effect on the evolution of irradiation-induced defects in materials,and contributes to our understanding of W performance under irradiation.

Load Balance Strategy of Data Routing Algorithm Using Semantics for Deduplication Clusters

The backup requirement of data centres is tremendous as the size of data created by human is massive and is increasing exponentially.Single node deduplication cannot meet the increasing backup requirement of data centres.A feasible way is the deduplication cluster,which can meet it by adding storage nodes.The data routing strategy is the key of the deduplication cluster.DRSS（data routing strategy using semantics） improves the storage utilization of MCS（minimum chunk signature） data routing strategy a lot.However,for the large deduplication cluster,the load balance of DRSS is worse than MCS.To improve the load balance of DRSS,we propose a load balance strategy used for DRSS,namely DRSSLB.When a node is overloaded,DRSSLB iteratively migrates the current smallest container of the node to the smallest node in the deduplication cluster until this overloaded node becomes non-overloaded.A container is the minimum unit of data migration.Similar files sharing the same features or file names are stored in the same container.This ensures the similar data groups are still in the same node after rebalancing the nodes.We use the dataset from the real world to evaluate DRSSLB.Experimental results show that,for various numbers of nodes of the deduplication cluster,the data skews of DRSSLB are under predefined value while the storage utilizations of DRSSLB do not nearly increase compared with DRSS,with the low penalty（the data migration rate is only6.5% when the number of nodes is 64）.

In vivo field recordings effectively monitor the mouse cortex and hippocampus under isoflurane anesthesia

Isoflurane is a widely used inhaled anesthetic in the clinical setting. However, the mechanism underlying its effect on consciousness is under discussion. Therefore, we investigated the effect of isoflurane on the hippocampus and cortex using an in vivo field recording approach. Our results showed that 1.3%, 0.8%, and 0.4% isoflurane exerted an inhibitory influence on the mouse hippocampus and cortex. Further, high frequency bands in the cortex and hippocampus showed greater suppression with increasing isoflurane concentration. Our findings suggest that in vivo field recordings can monitor the effect of isoflurane anesthesia on the mouse cortex and hippocampus.

Usefulness of interferon-γrelease assay for the diagnosis of sputum smear-negative pulmonary and extra-pulmonary TB in Zhejiang Province,China

Background:Quick diagnosis of smear-negative pulmonary tuberculosis(TB)and extra-pulmonary TB are urgently needed in clinical diagnosis.Our research aims to investigate the usefulness of the interferon-γrelease assay(IGRA)for the diagnosis of smear-negative pulmonary and extra-pulmonary TB.Methods:We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients(including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients),113 extra-pulmonary TB patients,81 patients with other pulmonary diseases and 100 healthy controls.Blood samples for the TB-Ab test and the TB-IGRA were collected,processed,and interpreted according to the manufacturer’s protocol.Results:The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8%(109 of 120)and 89.6%(241 of 269),respectively.There was no statistically significant difference of its performance between these two sample sets(P>0.05).The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0%(350 of 389)and 87.6%(99 of 113),respectively,which was not significantly different(P>0.05).Conclusions:In this work,the total detection ratio using TB-IGRA was 89.4%,therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.

Role of ecological approaches to eliminating schistosomiasis in Eryuan County evaluated by system modelling

Background:Schistosomiasis was severely prevalent in Yunnan Province,and it is difficult to achieve its elimination by convention approaches due to complexity of the nature.We explored the comprehensive model to eliminate schistosomiasis in Eryuan County,Yunnan Province,the People’s Republic of China,through integration with the ecological protection programme in Erhai Lake,in order to promote an efficient elimination strategy.We expected that this model is able to be tailored to other local settings,which help achieve the goal of precisely eliminating the disease in Yunnan Province.Methods:Eryuan County of Yunnan Province was chosen as the study area,where the data on environmental protection activities in Erhai Lake and on the schistosomiasis control programme were collected through different departments of Erhai County government since 2015.System modelling was performed using system dynamics software to establish a simulation model in order to evaluate the effectiveness of intervention activities.Results:Ecological approaches to control schistosomiasis in Eryuan County consist of three major components:(i)implementing precise interventions to stop schistosomiasis transmission by means of controlling the source of infection,blocking the biological transmission chains and cutting off the route of disease transmission;(ii)employing ecological approaches to improve the co-effectiveness of environmental protection and schistosomiasis prevention in the study area;and(iii)strengthening the professional skills of personnel involving in the schistosomiasis control programme.Simulation results showed that this strategy could speed up the progress of schistosomiasis control programme moving from the control stage to the elimination stage.Conclusions:Ecological approaches implemented in schistosomiasis endemic areas of the Eryuan region are able to improve the co-effectiveness of environmental protection and schistosomiasis control,providing a new avenue for eliminating schistosomiasis thanks to the application of precise interventions.

Total Arterial Off-Pump Coronary Artery Bypass Grafting： A 1O-Year Experience

Background： Arterial grafts had better mid-term and long-term patency than saphenous vein grafts in coronary artery bypass grafting （CABG）. We summarized our experience with total arterial off-pump coronary artery bypass grafting （OPCAB） and assessed the early clinical results, surgical complications, and follow-up. Methods： From January 2007 to May 2017,508 coronary artery disease patients undergoing total arterial OPCAB were enrolled. Clinical features, approaches, outcomes of surgical treatments, and follow-up data of these patients were studied retrospectively. A total of 122 patients underwent single left internal mammary artery （IMA）-left anterior descending artery grafts, whereas the other 386 patients underwent multiple vessel grafts. Results： The average distal anastomosis was 2.34 ± 0.97 （range： 1-4）. All the patients were discharged from hospital except one died. A total of 457 （90.32%） patients were followed up. In the 4-, 7-, and 10-year follow-up groups, the rate of death from any cause was 1.19%, 6.47%, and 10.67%; rate of cardiac death was 0.60%, 2.88%, and 3.33%; rate of repeat revascularization was 0.00%, 3.60%. and 8.67%; rate ofischemic symptoms was 1.79%, 7.91%, and 11.33%; and incidence of stroke was 2.38%, 4.32%, and 6.67%, respectively. Poor medication adherence was observed in 9.38% of the follow-up population. Conclusions： Total arterial OPCAB with bilateral IMA, radial artery, and right gastroepiploic artery grafting yielded satisfactory early and midterm outcomes in this patient group, without a significant increase in early mortality or morbidity. Moreover, the long-term outcomes are also positive.

Kinetic Monte Carlo code development and application on the formation of hydrogen-vacancy clusters in tungsten

We have developed an object kinetic Monte Carlo(OKMC)code and simulated hydrogen-vacancy clustering behavior and dependence on temperature and hydrogen-vacancy ratio in tungsten.For each of the temperatures we simulated from 300 K to1000 K,H_nV clusters with smaller n form before those with larger n.The elevating temperature leads to a decrease in hydrogen vacancies:H_(10)V and H_9V clusters dominate at 300 K and 600 K,whereas H_5V,H_6V,and H_7V clusters dominate when the temperature reaches 1000 K.Furthermore,only H_nV clusters with smaller n formed when a lower hydrogen-vacancy ratio was used due to insufficient availability of hydrogen atoms to occupy vacancies.The results suggest hydrogen emission occurs very rarely at lower temperatures,while higher temperatures facilitate the dissociation of hydrogen from H_nV clusters.

Synergy and Redundancy in a Signaling Cascade with Different Feedback Mechanisms

Feedback plays an important role in various biological signal transmission systems. In this paper, a signaling cascade system(including three layers: input(S), intermediate(V), output(X) components) is employed to study the fluctuations and net synergy in information transmission, in which the V component is regulated by itself or the X component, and each feedback on V is either positive or negative. The Fano factor, the net synergy, and the signalto-noise ratio(SNR) of signaling cascade with the four possible feedback types are theoretically derived by using linear noise approximation of the master equation, and the ability of information transmission through the signaling cascade is characterized by using the partial information decomposition of information theory. It is found that the signaling cascade exhibits different responses to the four feedback mechanisms, which depend on the relationships between degradation rates of components. Our results not only clarify the dependence of the Fano factor, net synergy, and SNR on the feedback regulations with the varying of degradation rates of components, but also imply that living cells could utilize different feedback mechanisms to adapt to the external fluctuating environments.

Protecting User Privacy in a Multi-Path Information-Centric Network Using Multiple Random-Caches

In-network caching is a fundamental mechanism advocated by information-centric networks （ICNs） for efficient content delivery. However, this new mechanism also brings serious privacy risks due to cache snooping attacks. One effective solution to this problem is random-cache, where the cache in a router randomly mimics a cache hit or a cache miss for each content request/probe. In this paper, we investigate the effectiveness of using multiple random-caches to protect cache privacy in a multi-path ICN. We propose models for characterizing the privacy of multi-path ICNs with random-caches, and analyze two different attack scenarios： 1） prefix-based attacks and 2） suffix-based attacks. Both homogeneous and heterogeneous caches are considered. Our analysis shows that in a multi-path ICN an adversary can potentially gain more privacy information by adopting prefix-based attacks. Furthermore, heterogeneous caches provide much better privacy protection than homogeneous ones under both attacks. The effect of different parameters on the privacy of multi-path random-caches is further investigated, and the comparison with its single-path counterpart is carried out based on numerical evaluations. The analysis and results in this paper provide insights in designing and evaluating multi-path ICNs when we take privacy into consideration.