Severe Global Environmental Issues Caused by Canada’s Record-Breaking Wildfires in 2023

Due to the record-breaking wildfires that occurred in Canada in 2023,unprecedented quantities of air pollutants and greenhouse gases were released into the atmosphere.The wildfires had emitted more than 1.3 Pg CO_(2)and 0.14 Pg CO_(2)equivalent of other greenhouse gases(GHG)including CH4 and N_(2)O as of 31 August.The wildfire-related GHG emissions constituted more than doubled Canada’s planned cumulative anthropogenic emissions reductions in 10 years,which represents a significant challenge to climate mitigation efforts.The model simulations showed that the Canadian wildfires impacted not only the local air quality but also that of most areas in the northern hemisphere due to long-range transport,causing severe PM_(2.5)pollution in the northeastern United States and increasing daily mean PM_(2.5)concentration in northwestern China by up to 2μg m-3.The observed maximum daily mean PM_(2.5)concentration in New York City reached 148.3μg m-3,which was their worst air quality in more than 50 years,nearly 10 times that of the air quality guideline(i.e.,15μg m-3)issued by the World Health Organization(WHO).Aside from the direct emissions from forest fires,the peat fires beneath the surface might smolder for several months or even longer and release substantial amounts of CO_(2).The substantial amounts of greenhouse gases from forest and peat fires might contribute to the positive feedback to the climate,potentially accelerating global warming.To better understand the comprehensive environmental effects of wildfires and their interactions with the climate system,more detailed research based on advanced observations and Earth System Models is essential.

Aromatic Essential Oil Acupressure Combined with Music Therapy in Cancer Pain Management

Objective: To explore the effect of aroma oil acupressure combined with music therapy in pain intervention for tumor patients. Methods: 60 patients with malignant tumors accompanied by cancer pain who were hospitalized in the oncology department of a tertiary-level hospital in Jingzhou City, Hubei Province, from January 2022 to December 2022 were selected as the study subjects, and were divided into 30 cases in the control group and 30 cases in the intervention group according to the stratified sampling method. The control group was divided into 30 cases of control group and 30 cases of intervention group according to the stratified sampling method. The control group was given medicine according to the conventional step analgesia, and the intervention group was given medicine according to the conventional step analgesia with the addition of aromatic oil acupressure combined with music therapy, and the effect of the intervention was valued by the NRS, the SAS and the SDS. Results: The NRS, SAS and SDS of patients in the intervention group were lower than those in the control group (p Conclusion: Aromatic oil acupressure combined with music therapy can effectively improve the pain symptoms of tumor patients, relieve anxiety and improve the quality of sleep of patients. Combined with pharmacological methods of pain relief, it can reduce the dose of pain medication and the frequency of administration of medication, and find a safe, low-cost, non-pharmacological pain complementary alternative therapy for tumor patients with cancer pain.

Strengths, weaknesses, opportunities and threats (SWOT) analysis of reinitiation into methamphetamine abusers: qualitative findings from an exploration of methamphetamine abusers in Shanghai, China

Background Despite high relapse rate among methamphetamine (MA) abusers, there still have been little empirical data to date detecting the risk factors related to craving and relapse from the perspective of MA abusers. Therefore, the aim of this study was to use qualitative research methods exploring the strengths, weaknesses, opportunities and threat factors that could facilitate or impede individuals' abstinence in a real-life context from the perspectives of MA abusers. Aim To use qualitative research methods exploring the strengths, weaknesses, opportunities and threat factors relating to individuals' abstinence in a real-life context. Method Semistructured interviews were conducted with 32 MA abusers recruited in Shanghai guided by open-ended questions on narrating the real-life catalysts and inhibitors related to craving, initiation, relapse and abstinence. All data were transcribed verbatim and analysed using a strengths, weaknesses, opportunities and threats (SWOT) analysis. Results The results of the SWOT analysis revealed that contextual factors including peer influence, prevalence and availability of MA, familiar venue of MA use, discrimination, sexual behaviours, alcohol, emotional states and their attitudes towards smoking MA were important factors that contribute to reinitiation and relapse. Surveillance systems, antidrug social workers, vocational skills trainings, moving to another city and family responsibility might serve as counter measures targeti叩 those mentioned weaknesses and threats above. Conclusion This SWOT analysis highlights the complex nature of relapse. Comprehensive interventions strengtheni叩 coping skills such as virtual reality techniques are desperately needed to facilitate individuals1 sustained abstinence.

Pathogen development and host responses to Plasmopara viticola in resistant and susceptible grapevines:an ultrastructural study

The downy mildew disease in grapevines is caused by Plasmopara viticola.This disease poses a serious threat wherever viticulture is practiced.Wild Vitis species showing resistance to P.viticola offer a promising pathway to develop new grapevine cultivars resistant to P.viticola which will allow reduced use of environmentally unfriendly fungicides.Here,transmission and scanning microscopy was used to compare the resistance responses to downy mildew of three resistant genotypes of V.davidii var.cyanocarpa,V.piasesezkii and V.pseudoreticulata and the suceptible V.vinifera cultivar‘Pinot Noir’.Following inoculation with sporangia of P.viticola isolate‘YL’on V.vinifera cv.‘Pinot Noir’,the infection was characterized by a rapid spread of intercellular hyphae,a high frequency of haustorium formation within the host’s mesophyll cells,the production of sporangia and by the absence of host-cell necrosis.In contrast zoospores were collapsed in the resistant V.pseudoreticulata‘Baihe-35-1’,or secretions appeared arround stomata at the beginning of the infection period in V.davidii var.cyanocarpa‘Langao-5’and V.piasezkii‘Liuba-8’.The main characteristics of the resistance responses were the rapid depositions of callose and the appearance of empty hyphae and the plasmolysis of penetrated tissue.Moreover,collapsed haustoria were observed in V.davidii var.cyanocarpa‘Langao-5’at 5 days post inoculation(dpi)and in V.piasezkii‘Liuba-8’at 7 dpi.Lastly,necrosis extended beyond the zone of restricted colonization in all three resistant genotypes.Sporangia were absent in V.piasezkii‘Liuba-8’and greatly decreased in V.davidii var.cyanocarpa‘Langao-5’and in V.pseudoreticulata‘Baihe-35-1’compared with in V.vinifera cv.‘Pinot Noir’.Overall,these results provide insights into the cellular biological basis of the incompatible interactions between the pathogen and the host.They indicate a number of several resistant Chinese wild species that could be used in developing new cultivars having good levels of downy mildew resistance.

Repeated methamphetamine exposure decreases plasma brain-derived neurotrophic factor levels in rhesus monkeys

Background Brain-derived neurotrophic factor(BDNF)is known to prevent methamphetamine(METH)-induced neurotoxicity and plays a role in various stages of METH addiction.However,there is a lack of research with longitudinal design on changes in plasma BDNF levels in active METH-dependent individuals.Aims The aim of the study was to investigate changes in BDNF levels during METH self-administration in monkeys.Methods This study measured plasma BDNF levels in three male rhesus monkeys with continuous METH exposure and four male control rhesus monkeys without METH exposure.Changes in plasma BDNF levels were then assessed longitudinally during 40 sessions of METH self-administration in the three monkeys.Results Repeated METH exposure decreased plasma BDNF levels.Additionally,plasma BDNF decreased with long-term rather than short-term accumulation of METH during METH self-administration.Conclusions These findings may indicate that the changes in peripheral BDNF may reflect the quantity of accumulative METH intake during a frequent drug use period.

Clinical characteristics of hospitalised patients with schizophrenia who were suspected to have coronavirus disease(COVID-19)in Hubei Province,China

Background Since the outbreak of C0VID-19,no data have been available for hospitalised psychiatric patients who are suspected to have COVID-19.We performed a comprehensive investigation of the clinical features of hospitalised patients with schizophrenia with or without suspected COVID-19 in Hubei Province,China.Aim To explore the clinical characteristics of hospitalised patients with schizophrenia with suspected COVID-19 in Hubei Province,China.M ethods 21 hospitalised patients with schizophrenia with suspected COVID-19(COVID-19 suspected group)in the isolation ward of a mental health hospital in Wuhan and 30 hospitalised patients with schizophrenia(clean group)in the general ward of another mental health hospital in Yichang were recruited.We retrospectively reviewed their clinical characteristics,laboratory findings and chest CT results before 21 February 2020.We also compared the emotional and mental symptoms between the two groups.Results Medical records revealed that 21 COVID-19 suspected patients were transferred to the isolation ward between 30 January 2020 and 15 February 2020.The mean age(SD)of COVID-19 suspected patients was 43.1(2.6).12(57.1%)patients showed abnormalities on chest CT before onset of respiratory symptoms.14(66.7%)patients had psychiatric medications adjustment after detection of abnormal chest CT findings.By 21 February,one patient was confirmed to have COVID-19.Even though the remaining 20(95.2%)were negative for at least two reverse transcription PCR tests,11(52.4%)patients met the diagnostic criteria for clinically confirmed cases.Compared with patients in the clean group,patients in the suspected COVID-19 group showed significantly higher stress,depression and anxiety levels and poorer sleep quality.Conclusion Setting up an independent isolation ward for hospitalised psychiatric patients who are suspected to have symptoms of COVID-19 helped control the spread of the epidemic.Patients with schizophrenia suspected to have COVID-19 showed increased stress and mood and sleep disturbances,which should be appropriately managed.

Mechanisms of fracture propagation from multi-cluster using a phase field based HMD coupling model in fractured reservoir

Natural fractures(NFs)are common in shale and tight reservoirs,where staged multi-cluster fracturing of horizontal wells is a prevalent technique for reservoir stimulation.While NFs and stress interference are recognized as significant factors affecting hydraulic fracture(HF)propagation,the combined influence of these factors remains poorly understood.To address this knowledge gap,a novel coupled hydromechanical-damage(HMD)model based on the phase field method is developed to investigate the propagation of multi-cluster HFs in fractured reservoirs.The comprehensive energy functional and control functions are established,while incorporating dynamic fluid distribution between multiple perforation clusters and refined changes in rock mechanical parameters during hydraulic fracturing.The HMD coupled multi-cluster HF propagation model investigates various scenarios,including single HF and single NF,reservoir heterogeneity,single HF and NF clusters,and multi-cluster HFs with NF clusters.The results show that the HMD coupling model can accurately capture the impact of approach angle(θ),stress difference and cementation strength on the interaction of HF and NF.The criterion of the open and cross zones is not fixed.The NF angle(a)is not a decisive parameter to discriminate the interaction.According to the relationship between approach angle(θ)and NF angle(a),the contact relationship of HF can be divided into three categories(θ=a,θ<a,andθ>a).The connected NF can increase the complexity of HF by inducing it to form branch fracture,resulting in a fractal dimension of HF as high as2.1280 at angles of±45°.Inter-fracture interference from the heel to the toe of HF shows the phenomenon of no,strong and weak interference.Interestingly,under the influence of NFs,distant HFs from the injection can become dominant fractures.However,as a gradually increases,inter-fracture stress interference becomes the primary factor influencing HF propagation,gradually superseding the dominance of NF induced fractures.

Research progress in CALPHAD assisted metal additive manufacturing

Metal additive manufacturing(MAM)technology has experienced rapid development in recent years.As both equipment and materials progress towards increased maturity and commercialization,material metallurgy technology based on high energy sources has become a key factor influencing the future development of MAM.The calculation of phase diagrams(CALPHAD)is an essential method and tool for constructing multi-component phase diagrams by employing experimental phase diagrams and Gibbs free energy models of simple systems.By combining with the element mobility data and non-equilibrium phase transition model,it has been widely used in the analysis of traditional metal materials.The development of CALPHAD application technology for MAM is focused on the compositional design of printable materials,the reduction of metallurgical imperfections,and the control of microstructural attributes.This endeavor carries considerable theoretical and practical significance.This paper summarizes the important achievements of CALPHAD in additive manufacturing(AM)technology in recent years,including material design,process parameter optimization,microstructure evolution simulation,and properties prediction.Finally,the limitations of applying CALPHAD technology to MAM technology are discussed,along with prospective research directions.

Damping properties and mechanism of aluminum matrix composites reinforced with glass cenospheres

The damping properties were improved by preparing Al matrix composites reinforced with glass cenospheres through the pressure infiltration method.Transmission electron microscopy and scanning electron microscopy were employed to characterize the microstructure of the composites.The low-frequency damping properties were examined by using a dynamic mechanical thermal analyzer,aiming at exploring the changing trend of damping capacity with strain,temperature,and frequency.The findings demonstrated that the damping value rose as temperature and strain increased,with a maximum value of 0.15.Additionally,the damping value decreased when the frequency increased.Dislocation damping under strain and interfacial damping under temperature served as the two primary damping mechanisms.The increase in the density of dislocation strong pinning points following heat treatment reduced the damping value,which was attributed to the heat treatment enhancement of the interfacial bonding force of the composites.

Adaptive multi-channel Bayesian graph attention network for IoT transaction security

With the rapid advancement of 5G technology,the Internet of Things(IoT)has entered a new phase of appli-cations and is rapidly becoming a significant force in promoting economic development.Due to the vast amounts of data created by numerous 5G IoT devices,the Ethereum platform has become a tool for the storage and sharing of IoT device data,thanks to its open and tamper-resistant characteristics.So,Ethereum account security is necessary for the Internet of Things to grow quickly and improve people's lives.By modeling Ethereum trans-action records as a transaction network,the account types are well identified by the Ethereum account classifi-cation system established based on Graph Neural Networks(GNNs).This work first investigates the Ethereum transaction network.Surprisingly,experimental metrics reveal that the Ethereum transaction network is neither optimal nor even satisfactory in terms of accurately representing transactions per account.This flaw may significantly impede the classification capability of GNNs,which is mostly governed by their attributes.This work proposes an Adaptive Multi-channel Bayesian Graph Attention Network(AMBGAT)for Ethereum account clas-sification to address this difficulty.AMBGAT uses attention to enhance node features,estimate graph topology that conforms to the ground truth,and efficiently extract node features pertinent to downstream tasks.An extensive experiment with actual Ethereum transaction data demonstrates that AMBGAT obtains competitive performance in the classification of Ethereum accounts while accurately estimating the graph topology.

CircR-ZC3HC1 mediates MiR-384-5p/SIRT1 axis to promote neuronal autophagy and relieves ischemic stroke

Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms.Methods:Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected.Hippocampal neurons were treated with oxygen and glucose deprivation(OGD)to establish IS in vitro model.The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope.Cell apoptosis rate and the expression of cleaved caspase-3,Bax,and Bcl-2 were assessed byflow cytometry and western blotting.The binding relationships among circR-ZC3HC1,miR-384-5p,and SIRT1 were predicted and verified.Results:Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons.Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons,which could be reversed by further 3-MA treatment.Mechanistically,circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression.miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis.Conclusion:Collectively,circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis.

Life Review the Impact of Combined Watson Care Theory Intervention on Psychological Status and Quality of Life in Patients with Terminal Lung Cancer

Objective: To analyze the impact of combined Watson care theory intervention on the psychological state and quality of life in patients with terminal lung cancer. Methods: 72 patients with terminal lung cancer admitted from March 2021 to January 2024 were selected, which were divided into research group (life review combined with Watson care theory intervention) and control group (conventional intervention), with 36 cases each. Compare the nursing effect between the two groups. Results: The anxiety self-rating scale (SAS) and depression self-rating scale (SDS) scores were significantly lower than those of the control group, and the quality of life score was significantly higher than that of the control group (P < 0.05). Conclusion: Life review combined with Watson care theory intervention can improve the psychological state and improve the quality of life of patients with terminal lung cancer.

Effect of Micropapillary Pattern and Spread through Air Space in Patients with Lung Adenocarcinoma ≤ 2 cm

Objective: To analyze the relationship between micropapillary pattern (MIP) and tumor spread through air space (STAS) and postoperative survival rate in patients with lung adenocarcinoma ≤ 2 cm. Methods: Retrospective analyses were performed on clinical data of 575 patients with lung adenocarcinoma ≤ 2 cm, which were resected from 2009 to 2011. We analyzed the pathological findings on the resected specimens, with special reference to the presence/absence MIP and STAS, which have been reported to be a marker of poor prognosis of lung adenocarcinoma. Patients were divided into three according to the presence/absence of MIP and STAS: low-risk (MIP- STAS-), medium-risk (either MIP or STAS + (one plus)) and high-risk group (+/+: double plus). Endpoint was postoperative survival rate, which was compared among three groups. Results: There was no statistical difference in age, sex, and serum CEA level among three groups. In lobectomized patients, there was no statistical difference in prognosis among three groups;however, in sub-lobectomy group, patients with double + (+/+ for MIP and STAS) showed a lower survival rate than others (P < 0.001). Conclusion: The presence of MIP and STAS reduced the survival rate in sub-lobectomized patients.

黄山和沈阳大气冰核数浓度及核化机制对比分析

本研究利用Bigg型混合云室及静力真空水汽扩散云室FRIDGE,结合其他气象要素观测设备,对黄山及沈阳为地域代表的各自三层不同高度大气冰核数浓度进行梯度对比观测,得出黄山及沈阳为地域代表各自三层不同高度大气冰核数浓度随高度、时间、活化温度、活化湿度、粒径大小等的变化规律,并对不同时空条件、不同核化条件、不同粒子条件下大气冰核的凝结冻结核化和凝华核化机制进行对比分析。对黄山及沈阳大气冰核的浓度分别拟合参数化公式,对黄山及沈阳不同区域的人工增减雨作业提供研究基础。

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis

AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloeemodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-a and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury

AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group(CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD(CG + SJD) and a model group treated with SJD(MG + SJD), both of which were orally administered with SJD(5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male SpragueDawley rats were randomly divided into a CG, an AP model group(MG), and an SJD treated AP group(SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.RESULTS The MG + SJD displayed significantly shorter mean residence time(MRT) and higher clearance(CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve(AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin(IL)-6, IL-10, and tumor necrosis factor(TNF)-α levels in the MG were higher than those in the CG(P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG(P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG(P < 0.05).CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro-and antiinflammatory responses, which might guide the clinical application of SJD for AP treatment.

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study

Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01(a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma

Objective: This study aimed to compare the pharmacokinetic, pharmacodynamic and safety profiles of HLX01(a rituximab biosimilar) and reference rituximab sourced from China(Mab Thera?;rituximab-CN).Methods: Here we report the results of two phase 1 studies. In the phase 1 a, open-label, dose-escalation study(NCT03218072, CTR20140400), eligible patients received 250, 375 and 500 mg/m^(2) HLX01 sequentially at 7-day intervals, after confirming no dose-limiting toxicity(DLT). In the phase 1 b, double-blind study(NCT02584920,CTR20140764), eligible patients were given a single dose of 375 mg/m^(2) HLX01 or rituximab-CN. The primary endpoints included safety and tolerability parameters for the phase 1 a and the area under the plasma concentrationtime curve from time zero to day 91(AUC0-91 d) for the phase 1 b study. Equivalence was concluded if 90%confidence interval(90% CI) for the geometric least squares mean ratio(GLSMR) fell in the pre-specified equivalence criteria(80%-125%).Results: Between June 20, 2014 and January 5, 2015, 12 patients were enrolled in the phase 1 a study. The pharmacokinetics of HLX01 showed dose proportionality and accumulation to steady state. HLX01 was well tolerated, with no serious adverse events(AEs), discontinuations or DLTs. Between November 8, 2014 and August13, 2015, 87 eligible patients were enrolled in the phase 1 b study, including 43 who received HLX01 and 44 who were treated with rituximab-CN. The equivalence endpoint was met with GLSMR for AUC0-91 d being 89.6%(90% CI: 80.4%-99.8%). AEs, anti-drug antibodies, and CD19+ and CD20+ B lymphocyte counts were similar between the HLX01 and rituximab-CN treatment groups.Conclusions: Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma.HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles.

Effect of Sheng-jiang powder on multiple-organ inflammatory injury in acute pancreatitis in rats fed a high-fat diet

BACKGROUND Obesity worsens inflammatory organ injury in acute pancreatitis(AP), but there is no effective preventive strategy. Sheng-jiang powder(SJP) has been shown to alleviate multiple-organ inflammatory injury in rats with high-fat diet-induced obesity. Hence, SJP is supposed to have an effect on multiple-organ inflammatory injury in AP in rats fed a high-fat diet.AIM To explore how obesity may contribute to aggravating inflammatory organ injury in AP in rats and observe the effect of SJP on multiple-organ inflammatory injury in AP in rats fed a high-fat diet.METHODS Rats were randomly assigned to a control group(CG), an obese group(OG), and an SJP treatment group(SG), with eight rats per group. The rats in the OG and SG were fed a high-fat diet. From the third week, the rats in the SG were given oral doses of SJP(5 g/kg of body weight). After 12 wk, AP was induced in the three groups. Serum amylase level, body weight, Lee's index, serum biochemistry parameters, and serum inflammatory cytokine and tissue cytokine levels were assessed, and the tissue histopathological scores were evaluated and compared.RESULTS Compared with the CG, serum triglyceride, total cholesterol, interleukin-6, and interleukin-10 levels were significantly higher in the OG, and serum high-density lipoprotein cholesterol level was significantly lower in the OG. Moreover,enhanced oxidative damage was observed in the pancreas, heart, spleen, lung,intestine, liver, and kidney. Evidence of an imbalanced antioxidant defense system, especially in the pancreas, spleen, and intestine, was observed in the obese AP rats. Compared with the OG, serum high-density lipoprotein cholesterol, interleukin-10, and superoxide dismutase expression levels in the pancreas, spleen, and intestine were increased in the SG. Additionally, SJP intervention led to a decrease in the following parameters: body weight; Lee's index; serum triglyceride levels; serum total cholesterol levels; malondialdehyde expression levels in the pancreas, heart, spleen, lung, and liver; myeloperoxidase expression levels in the lung; and pathological scores in the liver.CONCLUSION Obesity may aggravate the inflammatory reaction and pathological multipleorgan injury in AP rats, and SJP may alleviate multiple-organ inflammatory injury in AP in rats fed a high-fat diet.