Objectives:Electronic health records(EHRs)offer valuable real-world data(RWD)for Chinese medicine research.However,significant methodological challenges remain in developing integrative Chinese-Western medicine(ICWM)d...Objectives:Electronic health records(EHRs)offer valuable real-world data(RWD)for Chinese medicine research.However,significant methodological challenges remain in developing integrative Chinese-Western medicine(ICWM)databases.This study aims to establish a best-practice methodological framework,referred to as BRIDGE,to guide the construction of ICWM databases using EHRs.Methods:We developed the methodological framework through a comprehensive process,including systematic literature review,synthesis of empirical experiences,thematic expert discussions,and consultation with an external panel to reach consensus.Results:The BRIDGE framework outlines 6 core components for ICWM-EHR database development:Overall design,database architecture,data extraction and linkage,data governance,data verification,and data quality evaluation.Key data elements include variables related to study population,treatment or exposure,outcomes,and confounders.These databases support various research applications,particularly in evaluating the effectiveness and safety of integrative therapies.To demonstrate its practical value,we developed an ICWM-EHR database on women’s reproductive lifespan,encompassing 2,064,482 patients.This database captures women’s health conditions across the life course,from reproductive age to older adulthood.Conclusions:The BRIDGE methodological framework provides a standardized approach to building high-quality ICWM-EHR databases.It offers a unique opportunity to strengthen the methodological rigor and real-world relevance of Chinese medicine research in integrated healthcare settings.展开更多
The course ROS Robot Programming Practice is designed to equip students with both the foundational principles and practical applications of the Robot Operating System(ROS)through structured instruction and hands-on ex...The course ROS Robot Programming Practice is designed to equip students with both the foundational principles and practical applications of the Robot Operating System(ROS)through structured instruction and hands-on exercises.This paper summarizes the course’s pedagogical approach and the insights gained from its implementation,focusing on key areas such as the practical teaching platform,instructional system,teaching methods,and evaluation mechanisms.The practical teaching platform incorporates robotic arms and mobile robots,along with commonly used sensors,to engage students and stimulate their interest in robotics.A well-structured teaching system is employed,guiding students through a series of experiments-ranging from basic tasks to modeling and simulation experiments,sensor experiments,mobile robot tasks,robotic arm exercises,and comprehensive project practices.Regarding teaching methods,a blended learning approach and progressive instructional model are utilized to ensure active student participation.This approach follows a logical progression,starting with fundamental ROS knowledge,advancing to robot applications,and culminating in comprehensive project-based practice.In terms of evaluation,a dual approach combining process and outcome assessments is employed,ensuring that students’performance is evaluated comprehensively through various metrics.展开更多
BACKGROUND Noninvasive tests are crucial for the management and follow-up of patients with autoimmune hepatitis,but their validation is limited because of insufficient data.AIM To investigate the diagnostic performanc...BACKGROUND Noninvasive tests are crucial for the management and follow-up of patients with autoimmune hepatitis,but their validation is limited because of insufficient data.AIM To investigate the diagnostic performance of three fibrosis noninvasive tests[FibroTest,vibration-controlled transient elastography(VCTE),and the fibrosis-4 index(FIB-4)and two activity biomarkers(alanine aminotransferase(ALT)and ActiTest].METHODS This study enrolled 103 patients for whom liver biopsy,hepatic elastography results,and laboratory markers were available.Diagnostic performance was assessed with receiver operating characteristic(ROC)curves,the Obuchowski measure(OM),and the Bayesian latent class model.RESULTS FibroTest and VCTE outperformed FIB-4 in cases of significant fibrosis(≥F2),with areas under the ROC curve of 0.83[95%confidence interval(CI):0.73-0.90],0.86(95%CI:0.77-0.92),and 0.71(95%CI:0.60-0.80),respectively.The mean(standard error)OM values were 0.92(0.01),0.93(0.01),and 0.88(0.02)for FibroTest,VCTE,and FIB-4,respectively;FibroTest and VCTE performed comparably,and both were superior to FIB-4(P=0.03 and P=0.005).The areas under the ROC curve values for activity biomarkers were 0.86(95%CI:0.76-0.92)for ActiTest and 0.84(95%CI:0.73-0.90)for ALT(P=0.06).The OM values for ActiTest and ALT were 0.92(0.02)and 0.90(0.02),respectively(P=0.005).CONCLUSION FibroTest and VCTE outperformed FIB-4 according to the OM.FibroTest-ActiTest facilitated the evaluation of both fibrosis and activity.展开更多
Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stage...Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stages,this process results in cirrhosis and liver failure.The disease belongs to cholangiopathies.The review addressed historical questions concerning:The history of the first mention of this disease;how its nomenclature was formed;when specific serological tests were discovered and their importance in the diagnosis of PBC;the history of ursodeoxycholic and other bile acids for the treatment of PBC;and the significance of modern data on impaired bicarbonate production by cholangiocytes in the pathogenesis of PBC.展开更多
To study the relationships between rock mass crack propagation and damage and confining pressure under blast impact loading during straight-hole cut blasting,tests were performed under different confining pressures.Th...To study the relationships between rock mass crack propagation and damage and confining pressure under blast impact loading during straight-hole cut blasting,tests were performed under different confining pressures.Then,the characteristics of rock mass crack development were analyzed,and the pressure resistance values of core samples before and after blasting were compared to study the trends of rock mass damage.Moreover,a three-dimensional numerical simulation model was established by LS-DYNA to analyze the stress wave propagation,cavity shape and crack propagation characteristics under different confining pressures.The propagation of rock blasting cracks is negatively correlated with the confining pressure.The greater the confining pressure,the shorter the crack development time.Additionally,the crack width is reduced from 0.4-1.7 to 0.04-1.4 mm,and the length is shortened from 280 to 120 mm.A comparison of the compressive strength revealed that blasting reduces the compressive strength of the rock mass.The greater the distance from the explosion source,the lower the degree of strength attenuation.An increase in the confining pressure can inhibit strength attenuation.Numerical simulations revealed that under the same confining pressure,the stress first peaks at the bottom of the blast hole.The greater the confining pressure,the longer the stress peak duration,the smaller the cavity volume,and the shorter the crack propagation length and depth.Under a confining pressure of 4 MPa,the longest crack was only 154.5 mm in length and 102 mm in depth.The research results provide a scientific basis for controlling rock damage and optimizing design in the excavation of deep rock roadways by blasting.展开更多
The gut microbiota(GM)is a highly dynamic ecology whose density and com-position can be influenced by a wide range of internal and external factors.Thus,“How do GM,which can have commensal,pathological,and mutualisti...The gut microbiota(GM)is a highly dynamic ecology whose density and com-position can be influenced by a wide range of internal and external factors.Thus,“How do GM,which can have commensal,pathological,and mutualistic rela-tionships with us,affect human health?”has become the most popular research issue in recent years.Numerous studies have demonstrated that the trillions of microorganisms that inhabit the human body can alter host physiology in a variety of systems,such as metabolism,immunology,cardiovascular health,and neurons.The GM may have a role in the development of a number of clinical disorders by producing bioactive peptides,including neurotransmitters,short-chain fatty acids,branched-chain amino acids,intestinal hormones,and secondary bile acid conversion.These bioactive peptides enter the portal circulatory system through the gut-liver axis and play a role in the development of chronic liver diseases,cirrhosis,and hepatic encephalopathy.This procedure is still unclear and quite complex.In this study,we aim to discuss the contribution of GM to the development of liver diseases,its effects on the progression of existing chronic liver disease,and to address the basic mechanisms of the intestinal microbiota-liver axis in the light of recent publications that may inspire the future.展开更多
BACKGROUND Pediatric kidney transplantation is the treatment of choice for children with endstage renal disease;however,access to transplantation remains limited in lowand middle-income countries.Uzbekistan had no pri...BACKGROUND Pediatric kidney transplantation is the treatment of choice for children with endstage renal disease;however,access to transplantation remains limited in lowand middle-income countries.Uzbekistan had no prior institutional experience in performing pediatric living donor kidney transplantation(LDKT).AIM To report the implementation,surgical protocols,and clinical outcomes of the first pediatric LDKT program in Uzbekistan.METHODS This retrospective single-center study analyzed the first 20 pediatric LDKTs performed between April 2023 and February 2025.All donors were related family members who underwent either open or laparoscopic hand-assisted nephrectomy.Pre-transplant immunologic workup included HLA typing and anti-HLA antibody screening using solid-phase assays.Perioperative management was guided by Enhanced Recovery After Surgery Society principles.Primary outcomes included operative metrics,perioperative complications,graft function,biopsyproven rejection,and patient/graft survival.Statistical analysis utilized descriptive statistics,Kaplan–Meier survival estimates,and Fisher’s exact test where applicable.RESULTS Donors included 13 women and 7 men(median age:38 years;range:31–50).Median operative times were 182.5 minutes for open nephrectomy and 198.5 minutes for laparoscopic nephrectomy.No major intraoperative complications occurred;one donor developed a postoperative wound seroma.All recipients(aged 87–207 months)exhibited immediate graft function,with no delayed graft function observed.Median cold and warm ischemia times were 15 minutes(range:10–138)and 35 minutes(range:18–40),respectively.Median serum creatinine decreased from 198μmol/L on postoperative day 1 to 54μmol/L by day 7.Three rejection episodes were reported,two of which occurred in sensitized recipients.Two graft losses were attributed to late rejection.One patient died from hemorrhagic stroke six months post-transplant.At 24 months,patient and graft survival rates were 95%and 90%,respectively.CONCLUSION The successful implementation of a pediatric living donor kidney transplantation program in Uzbekistan yielded favorable short-and intermediate-term outcomes,with high graft survival and low complication rates.This experience may provide a practical framework for initiating similar programs in other resource-constrained healthcare settings.展开更多
Birefringent crystals play an irreplaceable role in optical systems by adjusting the polarization state of light in optical devices.This work successfully synthesized a new thiophosphate phase ofβ-Pb_(3)P_(2)S_(8)thr...Birefringent crystals play an irreplaceable role in optical systems by adjusting the polarization state of light in optical devices.This work successfully synthesized a new thiophosphate phase ofβ-Pb_(3)P_(2)S_(8)through the high-temperature solid-state spontaneous crystallization method.Different from the cubicα-Pb_(3)P_(2)S_(8),theβ-Pb_(3)P_(2)S_(8)crystallizes in the orthorhombic Pbcn space group.Notably,β-Pb_(3)P_(2)S_(8)shows a large band gap of 2.37 e V in lead-based chalcogenides,wide infrared transparent window(2.5-15μm),and excellent thermal stability.Importantly,the experimental birefringence shows the largest value of0.26@550 nm in chalcogenides,even larger than the commercialized oxide materials.The Barder charge analysis result indicates that the exceptional birefringence effect is mainly from the Pb^(2+)and S^(2-)in the[Pb S_n]polyhedrons.Meanwhile,the parallelly arranged polyhedral layers could improve the structural anisotropic.Therefore,this work supports a new method for designing chalcogenides with exceptional birefringence effect in the infrared region.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies,with high recurrence rates after treatment.Identifying reliable biomarkers for predicting recurrence is essential for improving patient ou...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies,with high recurrence rates after treatment.Identifying reliable biomarkers for predicting recurrence is essential for improving patient outcomes.Hepatitis B corerelated antigen(HBcrAg)has shown potential as a predictive marker for HCC recurrence.AIM To evaluate the association between HBcrAg levels and the risk of HCC recurrence.METHODS A systematic review was conducted following PRISMA guidelines.PubMed,EMBASE,Web of Science,and the Cochrane Library were searched without restrictions on date or language.Observational studies reporting hazard ratios(HRs)for HBcrAg as a predictor of HCC recurrence were included.Data extraction and quality assessment were performed independently by two reviewers.Statistical analyses used a random-effects model to account for heterogeneity(I²≥50%),and sensitivity analysis was performed to ensure the robustness of the results.RESULTS A total of 1339 articles were initially identified,and 17 studies were included in the final meta-analysis after screening.The pooled analysis showed a significant association between elevated HBcrAg levels and HCC recurrence(HR=4.42,95%confidence interval:3.43-5.41)with substantial heterogeneity(I²=92.6%).Subgroup analysis revealed higher pooled HRs in studies with≥500 participants(HR=4.18)and HBcrAg cut-offs≥4.0 LogU/mL(HR=5.29).Studies with≥10 years of follow-up showed a lower HR(2.89)compared to those with<10 years(3.27).Patients treated with nucleos(t)ide analogs had a pooled HR of 1.98,while those without nucleos(t)ide analog had a higher HR of 3.87.Sensitivity analysis confirmed the robustness of the results,with no significant publication bias detected.CONCLUSION This meta-analysis provides strong evidence that elevated HBcrAg levels are associated with an increased risk of HCC recurrence.HBcrAg may serve as a valuable biomarker for predicting recurrence,aiding personalized management and surveillance strategies for HCC patients.展开更多
Coronavirus disease 2019(COVID-19)is a multi-system disease that can lead to various severe complications.Acute limb ischemia(ALI)has been increasingly recognized as a COVID-19-associated complication that often predi...Coronavirus disease 2019(COVID-19)is a multi-system disease that can lead to various severe complications.Acute limb ischemia(ALI)has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis.However,the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood.Hypercoagulability and thrombosis are considered important mechanisms,but we also emphasize the roles of vasospasm,hypoxia,and acidosis in the pathogenesis of the disease.The angiotensin-converting enzyme 2(ACE2)pathway,inflammation,and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19.Furthermore,we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic,age,and gender perspectives based on our analysis of molecular mechanisms.Additionally,we summarize therapeutic approaches such as use of the interleukin-6(IL-6)blocker tocilizumab,calcium channel blockers,and angiotensin-converting enzyme inhibitors,providing insights for the future treatment of coronavirus-associated limb ischemic diseases.展开更多
BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques...BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.展开更多
Stomata are tiny pores on the plant leaf surface that regulate the exchange of water and gases between the plant and the external environment.They are crucial for photosynthesis,water use efficiency(WUE),and the plant...Stomata are tiny pores on the plant leaf surface that regulate the exchange of water and gases between the plant and the external environment.They are crucial for photosynthesis,water use efficiency(WUE),and the plant’s ability to adapt to environmental changes.Stomatal movement is vital for understanding how plants adapt to environmental stress and optimize resource utilization.Changes in environmental conditions,especially the quality and intensity of light throughout the day,affect stomatal dynamics and diurnal behavior,which in turn impact photosynthetic efficiency and water-use efficiency.In this review,we summarize the biophysical principles and mechanisms of stomatal movement regulated by ion transport at the plasma membrane,vacuolar membrane and metabolic activity through persulfidation or S-nitrosylation modifications.Specifically,we focus on recent progress in the regulation of stomatal movement by different light qualities,and summarize the photochemical and biochemical events underlying photoreceptors as well as the knowledge of novel regulatory functions and signaling in the multilayer control of stomatal movement and environmental adaptation.Furthermore,as rising global temperatures and increased water needs of farming methods are expected to escalate future crop losses,we explore the potential of smart LED lighting and gene editing technology in enhancing photosynthetic efficiency and water-use efficiency,leading to increased crop biomass and higher crop yields.展开更多
Objectives:Exosomal long noncoding RNAs(lncRNAs)might facilitate epithelial–mesenchymal transition(EMT)in liver cancer after transarterial chemoembolization(TACE),thereby enhancing tumor cell invasiveness and migrati...Objectives:Exosomal long noncoding RNAs(lncRNAs)might facilitate epithelial–mesenchymal transition(EMT)in liver cancer after transarterial chemoembolization(TACE),thereby enhancing tumor cell invasiveness and migration.This study investigated the prognostic role of plasma exosomal long noncoding RNA-plasmacytoma variant translocation 1(lncRNA-PVT1)in TACE treated hepatocellular carcinoma(HCC).Methods:Plasma exosomal lncRNA-PVT1 was evaluated via qPCR before and after TACE.Hepatoma cell behavior was investigated in different HCC cell lines.A lncRNA-PVT1 plasmid was synthesized and overexpressed,and si-lncRNA PVT1 was transfected into poorly invasive cells to reveal its influence on cell characteristics.The lncRNA-PVT1–FoxM1 interaction was elucidated using a double-luciferase reporter gene assay.The effect of miRNA-345-5p on minimally invasive hepatoma cells was assessed.Three experimental groups were established:poorly invasive cells,poorly invasive cells co-cultured with exosomes from hypoxia-induced highly invasive cells,and poorly invasive cells co-cultured with normal hepatocyte exosomes.Liver cancer cells were subcutaneously inoculated into nude mice,with subsequent observations of weight,tumor formation,and tumor size.Results:We identified two lncRNAs(lncRNA-PVT1 and GAPLINC)associated with EMT in the hypoxic microenvironment of liver cancer.Cox multivariate regression analysis was used to establish a prognostic model distinguishing high-and low-risk groups.Hypoxia-induced HepG2 exosomes significantly promoted EMT in poorly invasive HCC cells.LncRNA-PVT1 overexpression and silencing altered E-cadherin,vimentin,and FoxM1 expression,cell proliferation,invasion,migration,and apoptosis.miR-345-5p directly targeted lncRNA-PVT1 and FoxM1,affecting downstream targets.In vivo,co-culturing poorly invasive hepatoma cells with exosomes from highly invasive cells increased tumor volumes,upregulated lncRNA-PVT1,FoxM1,Ki67,and MMP9 expression,and downregulated miR-345-5p expression.Conclusions:Plasma exosomal lncRNA-PVT1 expression is upregulated in highly invasive cells post-hypoxia,potentially serving as a biomarker for evaluating liver cancer prognosis after TACE.Through a miRNA-345-5p-mediated competing endogenous RNA mechanism,it promotes EMT in poorly invasive cells,likely contributing to recurrence and metastasis post-HCC interventional embolization.展开更多
1 制订中医药临床随机对照试验报告规范（CONSORT for TCM）的必要性中医对疾病及其治疗的认识有别于西医,尤其中医“辨证论治”和“临证察机”的治疗原则比西医分型分类更加复杂，其临床研究因而有不同于西医的特点。但无论多么复杂，...1 制订中医药临床随机对照试验报告规范（CONSORT for TCM）的必要性中医对疾病及其治疗的认识有别于西医,尤其中医“辨证论治”和“临证察机”的治疗原则比西医分型分类更加复杂，其临床研究因而有不同于西医的特点。但无论多么复杂，随机对照试验（RCT）仍是目前公认的中医药防治性研究偏倚可能性最小的设计方案。由于中医药临床试验采用RCT方案仅约30年，试验设计还需要深人探索，试验结果报告还不规范。2005年，中国循证医学中心对中医药临床“随机对照试验”的主要研究者进行电话采访，调查随机方法正确性。展开更多
AIM: To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameter...AIM: To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameters. METHODS: Twenty-five GISTs were examined by light microscopy and immunohistochemistry. c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index (MI), tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53. RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size. CONCLUSION: COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.展开更多
Laser cladding is a new surface repair method that can improve the wear and corrosion resistance of substrate surfaces.However,the cladding layer typically exhibits a rough surface,high hardness and large residual ten...Laser cladding is a new surface repair method that can improve the wear and corrosion resistance of substrate surfaces.However,the cladding layer typically exhibits a rough surface,high hardness and large residual tensile stress,and thus requires further machining and finishing.Ultrasonic rolling(U-rolling)is a highly efficient finishing and strengthening process that combines ultrasonic technology with traditional rolling(T-rolling).In this study,an ironbased alloy was coated onto the surface of H13 die steel using laser cladding,and the surface of the cladding layer was polished using U-rolling.The effects of U-rolling on the surface quality,corrosion resistance and friction and wear properties of the laser-cladding layer were investigated and compared with those obtained by T-rolling.The surface roughness of the U-rolled sample was only 1/4 that of the T-rolled sample.The hardness and residual compressive stress of the laser cladding layer after U-rolling were higher than those after T-rolling.Similarly,the surface corrosion resistance of the laser cladding layer after U-rolling was higher than that after T-rolling.U-rolling changed the surface roughness,grain size,and residual stress of the material and thus affected the corrosion resistance of the laser cladding layer.The friction coefficient and wear rate of the U-rolled surface of the cladding layer were lower than those of the T-rolled surface.In addition,the tribological properties of the cladding layer were found to be related to the rolling direction.When the friction direction of the sample was the same as the rolling direction,its friction and wear performance were higher than those when the two directions were perpendicular.展开更多
基金supported by the National Key Research&Development Program of China(No.2024YFC3505800)the National Natural Science Foundation of China(Nos.82474334,82474335 and 72174132)+3 种基金National Science Fund for Distinguished Young Scholars(No.82225049)the Key Research&Development Projects of Sichuan Provincial Department of Science and Technology(Nos.2024YFFK0174 and 2024YFFK0152)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Nos.ZYYC24010 and ZYGD23004)the Special Fund for Traditional Chinese Medicine of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2024zd023).
文摘Objectives:Electronic health records(EHRs)offer valuable real-world data(RWD)for Chinese medicine research.However,significant methodological challenges remain in developing integrative Chinese-Western medicine(ICWM)databases.This study aims to establish a best-practice methodological framework,referred to as BRIDGE,to guide the construction of ICWM databases using EHRs.Methods:We developed the methodological framework through a comprehensive process,including systematic literature review,synthesis of empirical experiences,thematic expert discussions,and consultation with an external panel to reach consensus.Results:The BRIDGE framework outlines 6 core components for ICWM-EHR database development:Overall design,database architecture,data extraction and linkage,data governance,data verification,and data quality evaluation.Key data elements include variables related to study population,treatment or exposure,outcomes,and confounders.These databases support various research applications,particularly in evaluating the effectiveness and safety of integrative therapies.To demonstrate its practical value,we developed an ICWM-EHR database on women’s reproductive lifespan,encompassing 2,064,482 patients.This database captures women’s health conditions across the life course,from reproductive age to older adulthood.Conclusions:The BRIDGE methodological framework provides a standardized approach to building high-quality ICWM-EHR databases.It offers a unique opportunity to strengthen the methodological rigor and real-world relevance of Chinese medicine research in integrated healthcare settings.
文摘The course ROS Robot Programming Practice is designed to equip students with both the foundational principles and practical applications of the Robot Operating System(ROS)through structured instruction and hands-on exercises.This paper summarizes the course’s pedagogical approach and the insights gained from its implementation,focusing on key areas such as the practical teaching platform,instructional system,teaching methods,and evaluation mechanisms.The practical teaching platform incorporates robotic arms and mobile robots,along with commonly used sensors,to engage students and stimulate their interest in robotics.A well-structured teaching system is employed,guiding students through a series of experiments-ranging from basic tasks to modeling and simulation experiments,sensor experiments,mobile robot tasks,robotic arm exercises,and comprehensive project practices.Regarding teaching methods,a blended learning approach and progressive instructional model are utilized to ensure active student participation.This approach follows a logical progression,starting with fundamental ROS knowledge,advancing to robot applications,and culminating in comprehensive project-based practice.In terms of evaluation,a dual approach combining process and outcome assessments is employed,ensuring that students’performance is evaluated comprehensively through various metrics.
文摘BACKGROUND Noninvasive tests are crucial for the management and follow-up of patients with autoimmune hepatitis,but their validation is limited because of insufficient data.AIM To investigate the diagnostic performance of three fibrosis noninvasive tests[FibroTest,vibration-controlled transient elastography(VCTE),and the fibrosis-4 index(FIB-4)and two activity biomarkers(alanine aminotransferase(ALT)and ActiTest].METHODS This study enrolled 103 patients for whom liver biopsy,hepatic elastography results,and laboratory markers were available.Diagnostic performance was assessed with receiver operating characteristic(ROC)curves,the Obuchowski measure(OM),and the Bayesian latent class model.RESULTS FibroTest and VCTE outperformed FIB-4 in cases of significant fibrosis(≥F2),with areas under the ROC curve of 0.83[95%confidence interval(CI):0.73-0.90],0.86(95%CI:0.77-0.92),and 0.71(95%CI:0.60-0.80),respectively.The mean(standard error)OM values were 0.92(0.01),0.93(0.01),and 0.88(0.02)for FibroTest,VCTE,and FIB-4,respectively;FibroTest and VCTE performed comparably,and both were superior to FIB-4(P=0.03 and P=0.005).The areas under the ROC curve values for activity biomarkers were 0.86(95%CI:0.76-0.92)for ActiTest and 0.84(95%CI:0.73-0.90)for ALT(P=0.06).The OM values for ActiTest and ALT were 0.92(0.02)and 0.90(0.02),respectively(P=0.005).CONCLUSION FibroTest and VCTE outperformed FIB-4 according to the OM.FibroTest-ActiTest facilitated the evaluation of both fibrosis and activity.
文摘Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stages,this process results in cirrhosis and liver failure.The disease belongs to cholangiopathies.The review addressed historical questions concerning:The history of the first mention of this disease;how its nomenclature was formed;when specific serological tests were discovered and their importance in the diagnosis of PBC;the history of ursodeoxycholic and other bile acids for the treatment of PBC;and the significance of modern data on impaired bicarbonate production by cholangiocytes in the pathogenesis of PBC.
基金The National Natural Science Foundation of China(No.51874189)the Shandong Provincial Natural Science Foundation(Nos.ZR2023ME106 and ZR2023ME055)the Open Fund Project of the Engineering Research Center of the Ministry of Education for Mining Underground Engineering(No.JYBGCZX2021102).
文摘To study the relationships between rock mass crack propagation and damage and confining pressure under blast impact loading during straight-hole cut blasting,tests were performed under different confining pressures.Then,the characteristics of rock mass crack development were analyzed,and the pressure resistance values of core samples before and after blasting were compared to study the trends of rock mass damage.Moreover,a three-dimensional numerical simulation model was established by LS-DYNA to analyze the stress wave propagation,cavity shape and crack propagation characteristics under different confining pressures.The propagation of rock blasting cracks is negatively correlated with the confining pressure.The greater the confining pressure,the shorter the crack development time.Additionally,the crack width is reduced from 0.4-1.7 to 0.04-1.4 mm,and the length is shortened from 280 to 120 mm.A comparison of the compressive strength revealed that blasting reduces the compressive strength of the rock mass.The greater the distance from the explosion source,the lower the degree of strength attenuation.An increase in the confining pressure can inhibit strength attenuation.Numerical simulations revealed that under the same confining pressure,the stress first peaks at the bottom of the blast hole.The greater the confining pressure,the longer the stress peak duration,the smaller the cavity volume,and the shorter the crack propagation length and depth.Under a confining pressure of 4 MPa,the longest crack was only 154.5 mm in length and 102 mm in depth.The research results provide a scientific basis for controlling rock damage and optimizing design in the excavation of deep rock roadways by blasting.
文摘The gut microbiota(GM)is a highly dynamic ecology whose density and com-position can be influenced by a wide range of internal and external factors.Thus,“How do GM,which can have commensal,pathological,and mutualistic rela-tionships with us,affect human health?”has become the most popular research issue in recent years.Numerous studies have demonstrated that the trillions of microorganisms that inhabit the human body can alter host physiology in a variety of systems,such as metabolism,immunology,cardiovascular health,and neurons.The GM may have a role in the development of a number of clinical disorders by producing bioactive peptides,including neurotransmitters,short-chain fatty acids,branched-chain amino acids,intestinal hormones,and secondary bile acid conversion.These bioactive peptides enter the portal circulatory system through the gut-liver axis and play a role in the development of chronic liver diseases,cirrhosis,and hepatic encephalopathy.This procedure is still unclear and quite complex.In this study,we aim to discuss the contribution of GM to the development of liver diseases,its effects on the progression of existing chronic liver disease,and to address the basic mechanisms of the intestinal microbiota-liver axis in the light of recent publications that may inspire the future.
文摘BACKGROUND Pediatric kidney transplantation is the treatment of choice for children with endstage renal disease;however,access to transplantation remains limited in lowand middle-income countries.Uzbekistan had no prior institutional experience in performing pediatric living donor kidney transplantation(LDKT).AIM To report the implementation,surgical protocols,and clinical outcomes of the first pediatric LDKT program in Uzbekistan.METHODS This retrospective single-center study analyzed the first 20 pediatric LDKTs performed between April 2023 and February 2025.All donors were related family members who underwent either open or laparoscopic hand-assisted nephrectomy.Pre-transplant immunologic workup included HLA typing and anti-HLA antibody screening using solid-phase assays.Perioperative management was guided by Enhanced Recovery After Surgery Society principles.Primary outcomes included operative metrics,perioperative complications,graft function,biopsyproven rejection,and patient/graft survival.Statistical analysis utilized descriptive statistics,Kaplan–Meier survival estimates,and Fisher’s exact test where applicable.RESULTS Donors included 13 women and 7 men(median age:38 years;range:31–50).Median operative times were 182.5 minutes for open nephrectomy and 198.5 minutes for laparoscopic nephrectomy.No major intraoperative complications occurred;one donor developed a postoperative wound seroma.All recipients(aged 87–207 months)exhibited immediate graft function,with no delayed graft function observed.Median cold and warm ischemia times were 15 minutes(range:10–138)and 35 minutes(range:18–40),respectively.Median serum creatinine decreased from 198μmol/L on postoperative day 1 to 54μmol/L by day 7.Three rejection episodes were reported,two of which occurred in sensitized recipients.Two graft losses were attributed to late rejection.One patient died from hemorrhagic stroke six months post-transplant.At 24 months,patient and graft survival rates were 95%and 90%,respectively.CONCLUSION The successful implementation of a pediatric living donor kidney transplantation program in Uzbekistan yielded favorable short-and intermediate-term outcomes,with high graft survival and low complication rates.This experience may provide a practical framework for initiating similar programs in other resource-constrained healthcare settings.
基金supported in part by the National Natural Science Foundation of China(No.52102218)the National Key Research and Development Program of China(No.2020YFA0710303)+2 种基金the Fujian Science&Technology Innovation Laboratory for Op-toelectronic Information of China(No.2021ZZ127)the Minjiang Scholar Professorship(No.GXRC-21004)the Natural Science Foundation of Fujian Province of China(No.2021J01594)。
文摘Birefringent crystals play an irreplaceable role in optical systems by adjusting the polarization state of light in optical devices.This work successfully synthesized a new thiophosphate phase ofβ-Pb_(3)P_(2)S_(8)through the high-temperature solid-state spontaneous crystallization method.Different from the cubicα-Pb_(3)P_(2)S_(8),theβ-Pb_(3)P_(2)S_(8)crystallizes in the orthorhombic Pbcn space group.Notably,β-Pb_(3)P_(2)S_(8)shows a large band gap of 2.37 e V in lead-based chalcogenides,wide infrared transparent window(2.5-15μm),and excellent thermal stability.Importantly,the experimental birefringence shows the largest value of0.26@550 nm in chalcogenides,even larger than the commercialized oxide materials.The Barder charge analysis result indicates that the exceptional birefringence effect is mainly from the Pb^(2+)and S^(2-)in the[Pb S_n]polyhedrons.Meanwhile,the parallelly arranged polyhedral layers could improve the structural anisotropic.Therefore,this work supports a new method for designing chalcogenides with exceptional birefringence effect in the infrared region.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common malignancies,with high recurrence rates after treatment.Identifying reliable biomarkers for predicting recurrence is essential for improving patient outcomes.Hepatitis B corerelated antigen(HBcrAg)has shown potential as a predictive marker for HCC recurrence.AIM To evaluate the association between HBcrAg levels and the risk of HCC recurrence.METHODS A systematic review was conducted following PRISMA guidelines.PubMed,EMBASE,Web of Science,and the Cochrane Library were searched without restrictions on date or language.Observational studies reporting hazard ratios(HRs)for HBcrAg as a predictor of HCC recurrence were included.Data extraction and quality assessment were performed independently by two reviewers.Statistical analyses used a random-effects model to account for heterogeneity(I²≥50%),and sensitivity analysis was performed to ensure the robustness of the results.RESULTS A total of 1339 articles were initially identified,and 17 studies were included in the final meta-analysis after screening.The pooled analysis showed a significant association between elevated HBcrAg levels and HCC recurrence(HR=4.42,95%confidence interval:3.43-5.41)with substantial heterogeneity(I²=92.6%).Subgroup analysis revealed higher pooled HRs in studies with≥500 participants(HR=4.18)and HBcrAg cut-offs≥4.0 LogU/mL(HR=5.29).Studies with≥10 years of follow-up showed a lower HR(2.89)compared to those with<10 years(3.27).Patients treated with nucleos(t)ide analogs had a pooled HR of 1.98,while those without nucleos(t)ide analog had a higher HR of 3.87.Sensitivity analysis confirmed the robustness of the results,with no significant publication bias detected.CONCLUSION This meta-analysis provides strong evidence that elevated HBcrAg levels are associated with an increased risk of HCC recurrence.HBcrAg may serve as a valuable biomarker for predicting recurrence,aiding personalized management and surveillance strategies for HCC patients.
基金supported by the Zhejiang Provincial Medical Scientific Research Program(No.2022RC136),China.
文摘Coronavirus disease 2019(COVID-19)is a multi-system disease that can lead to various severe complications.Acute limb ischemia(ALI)has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis.However,the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood.Hypercoagulability and thrombosis are considered important mechanisms,but we also emphasize the roles of vasospasm,hypoxia,and acidosis in the pathogenesis of the disease.The angiotensin-converting enzyme 2(ACE2)pathway,inflammation,and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19.Furthermore,we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic,age,and gender perspectives based on our analysis of molecular mechanisms.Additionally,we summarize therapeutic approaches such as use of the interleukin-6(IL-6)blocker tocilizumab,calcium channel blockers,and angiotensin-converting enzyme inhibitors,providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
基金This retrospective analysis incorporated data from two clinical trials(CTR20220854 and CTR20222843)sponsored by Chongqing Chenan Biopharmaceutical Co.,Ltd.and Jiangsu Hengrui Pharmaceuticals Co.,Ltd.However,these sponsors did not partake in the study design,data interpretation,or manuscript preparation.
文摘BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.
基金funded by the National Natural Science Foundation of China(Grant Nos.32272698,32441072,32122081)National Key Research and Development Program of China(Grant No.2023YFF1002000)+4 种基金Liaoning Province Youth Science Foundation A-Class Project(formerly Liaoning Natural Science Foundation Outstanding Youth Project,Grant No.2025-JQ-05)Liaoning Province’s Future Industry Frontier Technology Project(Grant Nos.2025JH2/101330184 and 2025JH2/101330185)National Postdoctoral Program for Innovative Talents(Grant No.BX20250016)Open Project Program of State Key Laboratory of Crop Stress Biology for Arid Areas of China(Grant No.SKLCSRHPKF2025017)HAAFS Science and Technology Innovation Special Project(Grant No.2023KJCXZX-JZS-10).
文摘Stomata are tiny pores on the plant leaf surface that regulate the exchange of water and gases between the plant and the external environment.They are crucial for photosynthesis,water use efficiency(WUE),and the plant’s ability to adapt to environmental changes.Stomatal movement is vital for understanding how plants adapt to environmental stress and optimize resource utilization.Changes in environmental conditions,especially the quality and intensity of light throughout the day,affect stomatal dynamics and diurnal behavior,which in turn impact photosynthetic efficiency and water-use efficiency.In this review,we summarize the biophysical principles and mechanisms of stomatal movement regulated by ion transport at the plasma membrane,vacuolar membrane and metabolic activity through persulfidation or S-nitrosylation modifications.Specifically,we focus on recent progress in the regulation of stomatal movement by different light qualities,and summarize the photochemical and biochemical events underlying photoreceptors as well as the knowledge of novel regulatory functions and signaling in the multilayer control of stomatal movement and environmental adaptation.Furthermore,as rising global temperatures and increased water needs of farming methods are expected to escalate future crop losses,we explore the potential of smart LED lighting and gene editing technology in enhancing photosynthetic efficiency and water-use efficiency,leading to increased crop biomass and higher crop yields.
基金the Ethics Committee of the West China Hospital,Sichuan University(No.2018256)the Animal Ethical and Welfare Committee of Sichuan University in China(No.20211218A).
文摘Objectives:Exosomal long noncoding RNAs(lncRNAs)might facilitate epithelial–mesenchymal transition(EMT)in liver cancer after transarterial chemoembolization(TACE),thereby enhancing tumor cell invasiveness and migration.This study investigated the prognostic role of plasma exosomal long noncoding RNA-plasmacytoma variant translocation 1(lncRNA-PVT1)in TACE treated hepatocellular carcinoma(HCC).Methods:Plasma exosomal lncRNA-PVT1 was evaluated via qPCR before and after TACE.Hepatoma cell behavior was investigated in different HCC cell lines.A lncRNA-PVT1 plasmid was synthesized and overexpressed,and si-lncRNA PVT1 was transfected into poorly invasive cells to reveal its influence on cell characteristics.The lncRNA-PVT1–FoxM1 interaction was elucidated using a double-luciferase reporter gene assay.The effect of miRNA-345-5p on minimally invasive hepatoma cells was assessed.Three experimental groups were established:poorly invasive cells,poorly invasive cells co-cultured with exosomes from hypoxia-induced highly invasive cells,and poorly invasive cells co-cultured with normal hepatocyte exosomes.Liver cancer cells were subcutaneously inoculated into nude mice,with subsequent observations of weight,tumor formation,and tumor size.Results:We identified two lncRNAs(lncRNA-PVT1 and GAPLINC)associated with EMT in the hypoxic microenvironment of liver cancer.Cox multivariate regression analysis was used to establish a prognostic model distinguishing high-and low-risk groups.Hypoxia-induced HepG2 exosomes significantly promoted EMT in poorly invasive HCC cells.LncRNA-PVT1 overexpression and silencing altered E-cadherin,vimentin,and FoxM1 expression,cell proliferation,invasion,migration,and apoptosis.miR-345-5p directly targeted lncRNA-PVT1 and FoxM1,affecting downstream targets.In vivo,co-culturing poorly invasive hepatoma cells with exosomes from highly invasive cells increased tumor volumes,upregulated lncRNA-PVT1,FoxM1,Ki67,and MMP9 expression,and downregulated miR-345-5p expression.Conclusions:Plasma exosomal lncRNA-PVT1 expression is upregulated in highly invasive cells post-hypoxia,potentially serving as a biomarker for evaluating liver cancer prognosis after TACE.Through a miRNA-345-5p-mediated competing endogenous RNA mechanism,it promotes EMT in poorly invasive cells,likely contributing to recurrence and metastasis post-HCC interventional embolization.
文摘1 制订中医药临床随机对照试验报告规范（CONSORT for TCM）的必要性中医对疾病及其治疗的认识有别于西医,尤其中医“辨证论治”和“临证察机”的治疗原则比西医分型分类更加复杂，其临床研究因而有不同于西医的特点。但无论多么复杂，随机对照试验（RCT）仍是目前公认的中医药防治性研究偏倚可能性最小的设计方案。由于中医药临床试验采用RCT方案仅约30年，试验设计还需要深人探索，试验结果报告还不规范。2005年，中国循证医学中心对中医药临床“随机对照试验”的主要研究者进行电话采访，调查随机方法正确性。
文摘AIM: To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameters. METHODS: Twenty-five GISTs were examined by light microscopy and immunohistochemistry. c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index (MI), tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53. RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size. CONCLUSION: COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.
基金National Natural Science Foundation of China(Grant No.51975123)Fujian Provincial Natural Science Foundation of China(Grant No.2020J05115)+1 种基金Fuzhou Municipal Science and Technology Plan Project of China(Grant No.2020-PT-148)Quanzhou Municipal Science and Technology Plan Project of China(Grant No.2020C043R).
文摘Laser cladding is a new surface repair method that can improve the wear and corrosion resistance of substrate surfaces.However,the cladding layer typically exhibits a rough surface,high hardness and large residual tensile stress,and thus requires further machining and finishing.Ultrasonic rolling(U-rolling)is a highly efficient finishing and strengthening process that combines ultrasonic technology with traditional rolling(T-rolling).In this study,an ironbased alloy was coated onto the surface of H13 die steel using laser cladding,and the surface of the cladding layer was polished using U-rolling.The effects of U-rolling on the surface quality,corrosion resistance and friction and wear properties of the laser-cladding layer were investigated and compared with those obtained by T-rolling.The surface roughness of the U-rolled sample was only 1/4 that of the T-rolled sample.The hardness and residual compressive stress of the laser cladding layer after U-rolling were higher than those after T-rolling.Similarly,the surface corrosion resistance of the laser cladding layer after U-rolling was higher than that after T-rolling.U-rolling changed the surface roughness,grain size,and residual stress of the material and thus affected the corrosion resistance of the laser cladding layer.The friction coefficient and wear rate of the U-rolled surface of the cladding layer were lower than those of the T-rolled surface.In addition,the tribological properties of the cladding layer were found to be related to the rolling direction.When the friction direction of the sample was the same as the rolling direction,its friction and wear performance were higher than those when the two directions were perpendicular.
