ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang （M-XSLJZ） on intestinal-derived lipopolysaccharide （LPS）-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups （n=10）： blank control （CON）， high-fat diet without spleen deficiency （HFD）， high-fat diet with spleen deficiency （SD-HFD）， M-XSLJZ low-， medium-， and high-dose groups （XS-L， XS-M， XS-H）， and western medicine control （R）. Spleen deficiency was induced in SD-HFD， XS-L， XS-M， XS-H， and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet， while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling， rats were treated for 8 weeks： M-XSLJZ was administered at 3.51， 7.02， 14.04 g·kg^-1 in XS-L， XS-M， and XS-H groups， respectively. The R group received 9×10^-4 g·kg^-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin （HE） staining was used to evaluate the pathological conditions of the liver， and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS， portal vein serum LPS， LPS-binding protein （LBP）， serum interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4， MyD88， NF-κB p65， and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6， TNF-α， and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the CON group， the SD-HFD group showed a decrease in D-xylose excretion （P<0.01）. TC， TG， HDL-C， and LDL-C increased （P<0.05， P<0.01）. A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS， portal LPS， and LBP increased （P<0.05， P<0.01）. The levels of serum IL-6， TNF-α， and IL-1β increased （P<0.01）. The expression of CD86 was upregulated （P<0.01）， and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4， MyD88， and p-p65 in Kupffer cells increased （P<0.01）. The mRNA and protein levels of IL-6， TNF-α， and IL-1β increased （P<0.05， P<0.01）. Compared with the HFD group， the SD-HFD group exhibited decreased D-xylose excretion （P<0.01）， higher HDL-C， LDL-C （P<0.05）， increased portal LBP and LPS （P<0.05）， increased serum IL-6 and TNF-α （P<0.01）， upregulated CD86 （P<0.01）， enhanced CD68/TLR4 co-expression， and higher TNF-α mRNA/protein （P<0.05）. Compared with the SD-HFD group， all M-XSLJZ treatment groups showed reduced TC， TG， and LDL-C （P<0.05， P<0.01）. XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS， portal LPS， and LBP levels （P<0.05， P<0.01）. All M-XSLJZ treatment groups exhibited reduced serum IL-6， IL-1β， and TNF-α （P<0.01）. The XS-H group showed downregulated CD86 （P<0.01） and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4， MyD88， and p-NF-κB p65 in Kupffer cells （P<0.01）. XS-H and R groups showed lower IL-6， TNF-α， and IL-1β mRNA/protein （P<0.05， P<0.01）. ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Objective To explore the mechanism of modified Xiangsha Liujunzi Decoction in regulating apolipoproteinA-Ⅰ (apoA-Ⅰ),improving endoplasmic reticulum stress,regulating glucose and lipid metabolism,and preventing and treating dyslipidemia in mice. Methods Wild-type (WT) C57BL/6J mice were randomly divided into the WT,WT+high-fat diet(HFD),and WT+HFD+Xiangsha Liujunzi Decoction(XSLJZ) groups according to the random number table method. ApoA-Ⅰ-/-mice were randomly divided into the apoA-Ⅰ-/-,apoA-Ⅰ-/-+HFD,and apoA-Ⅰ-/-+HFD+XSLJZ groups (n=10) according to the random number table method. D12492 was used for HFD feeding to establish a hyperlipidemic mouse model. Modified XSLJZ (23.66g/kg) was administered daily by gavage from the ninth week. Serum and liver tissue were collected for testing after 4 weeks. An automatic biochemical analyzer was used to detect blood lipid levels;an enzyme-linked immunosorbent assay was used to detect serum fasting blood glucose (FBG) and insulin (INS) levels,and the INS resistance index (HOMA-IR) was calculated. Hematoxylin and eosin staining was used to observe the pathological changes in the liver. Oil red O staining was used to observe the lipid deposition in the liver. TG levels in liver tissue were detected using the microplate method. Real-time PCR was used to detect apoA-Ⅰ,glucose-regulated proteins (GRP78),sterol regulatory element binding protein-1c (SREBP-1c),acetyl CoA carboxylase 1 (ACC1),and fatty acid synthase (FASN) mRNA expression levels in liver tissue. The WES fully automated protein expression analysis system was used to detect apoA-Ⅰ,GRP78,inositol-requiring enzyme 1 (IRE1),p-IRE1,c-Jun N-terminal kinase (JNK),p-JNK,insulin receptor substrate (IRS1),p-IRS1,protein kinase B (Akt),p-Akt,SREBP-1c,ACC1,and FASN protein expression levels in liver tissue. Results Compared to the WT group,the WT+HFD group showed a significant increase in serum lipids,FBG,INS levels,and the HOMA-IR index (P<0.05). The orange-red lipid droplets in liver tissue increased,fat vacuoles were apparent,and TG levels were significantly increased. ApoA-Ⅰ mRNA and protein expression levels were significantly reduced,whereas GRP78,SREBP-1c,ACC1,and FASN mRNA expression levels were increased,GRP78,SREBP-1c,ACC1,and FASN protein levels and the IRE1,JNK,IRS1,and Akt phosphorylation degree were increased (P<0.05). The serum TG,HDL-C,LDL-C,FBG,and INS levels and the HOMA-IR index in the WT+HFD group were significantly reduced after administering modified XSLJZ (P<0.05). The orange-red lipid droplets in liver tissue were significantly reduced,fat vacuolization was alleviated,and TG levels were significantly reduced,ApoA-Ⅰ mRNA and protein expression levels were significantly increased,whereas GRP78,SREBP-1c,ACC1,and FASN mRNA expression levels were reduced,GRP78,SREBP-1c,ACC1,and FASN protein expression levels and the IRE1,JNK,IRS1,and Akt phosphorylation degree were reduced (P<0.05). Compared to the WT+HFD group,the TG,LDL-C,and FBG levels and HOMA-IR index in the serum of the apoA-Ⅰ-/-+HFD group were significantly increased,whereas the HDL-C levels were significantly decreased (P<0.05). Diffuse orange-red lipid droplets in liver tissue and a significant increase in fat vacuoles were observed. Furthermore,TG levels were significantly increased,SREBP-1c,ACC1,FASN mRNA,SREBP-1c,and ACC1 protein expression levels and IRE1,JNK,IRS1,and Akt phosphorylation levels were significantly increased (P<0.05). Compared to the WT+HFD+XSLJZ group,the apoA-Ⅰ-/-+HFD+XSLJZ group showed a significant increase in serum TG,LDL-C,FBG,and INS levels,and the HOMA-IR index,whereas HDL-C levels decreased significantly (P<0.05). The deposition of orange-red lipid droplets in liver tissue improved,and TG levels significantly decreased,GRP78,SREBP-1c,ACC1,and FASN mRNA expression levels,GRP78,SREBP-1c,and ACC1 protein levels,and IRE1,JNK,IRS1,and Akt phosphorylation levels increased (P<0.05). Conclusion Modified XSLJZ improves liver glucose and lipid metabolism disorder by regulating apoA-Ⅰ to alleviate endoplasmic reticulum stress.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Objective·To develope an auditory brainstem implant(ABI)vocoder based on cochlear implant(CI)vocoder characteristics and ABI electrode array topology,and to verify its reliability.Methods·An"n-of-m"coding strategy CI/ABI vocoder was constructed based on MATLAB.Within each frame,only the envelopes of the n channels with the highest energy were selected.The interaction coefficient(IC)(range:1?3),channel numbers(range:5?22),and electrode array topology(CI/ABI)were adjustable parameters,allowing for the synthesis of simulated speech.Psychoacoustic evaluation was employed,recruiting normal hearing subjects to perform closed-set simulated phoneme perception.The phoneme recognition accuracy(20 vowel questions/condition,11 consonant questions/condition)was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability.Results·The vocoder successfully synthesized all test stimuli.In the closed-set CI-simulated speech recognition,the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature(P＞0.05).The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature(vowel|d|=1.6%vs.20%,consonant|d|=8.4%vs.9.9%),thus determining the optimal interaction coefficient of this model as 2.Subsequently,when modifying the electrode array topology to ABI,it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group,consistent with the reported literature.The simulated vowel and consonant accuracy within the 5?8 channel range for ABI showed no significant difference(P＞0.05),also aligning with the trend reported in the literature.Conclusion·A CI/ABI vocoder based on"n-of-m"coding strategy is established and the optimal IC is determined.The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments.It provides suitable technical means for validating ABI-specific coding strategies.

Objective:The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) .Methods:This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared.Results:①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD ( P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ( R2=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion:sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.

Objective:To explore the changes in behavioral indexes and electroencephalogram (EEG) in the stage of temporal memory retrieval under different extraction times.Methods:A total of 30 healthy subjects were randomly selected from Shanghai University of Science and Technology in November 2022. The reaction time and EEG of the subjects in the 1 500 ms stage of temporal memory retrieval were recorded by a reproduction method of time estimation task. The memory error rate, precision, accuracy, and low-frequency power of EEG were calculated, and time-frequency analysis and traceability analysis were carried out. Pearson correlation analysis was used to analyze the correlation between memory error rate, accuracy, θ rhythm, and β rhythm.Results:The main effects of time difference and memory precision between retrieval times were found [ F(3, 1 196) = 2.932, P = 0.033; F(3, 1 196) = 3.191, P = 0.026], and they increased with the extraction times. There was no main effect on memory accuracy, but as the number of extractions increases, the average accuracy increased. With the increase in memory retrieval times, the power of θ rhythm in the left frontal lobe gradually increased [ F(3, 116) = 2.668, P = 0.035], and the average power of β rhythm in the middle frontal lobe gradually decreased [ F(3, 116) = 2.810, P = 0.029]. The differences in current density distribution in the somatosensory cortex (BA7), dorsolateral prefrontal cortex (BA9), and premotor cortex (BA6) increased in the first and second, second and third, and third and fourth memory retrievals ( P < 0.01). The θ rhythm was positively correlated with memory accuracy ( r = 0.258, P < 0.05), and the β rhythm was negatively correlated with memory precision ( r = ? 0.404, P < 0.01). Conclusions:In the stage of temporal memory extraction, increasing the number of temporal memory extraction times can reduce the memory error rate and improve accuracy. Memory accuracy is related to the power of the θ rhythm in the left frontal lobe and the power of the β rhythm in the middle frontal lobe.

"Shaoyang as the pivot"is one of the important concepts in the theory of traditional Chinese medicine.It is believed that shaoyang is located between half exterior and half interior,which reaches the muscular striae and the exterior and connects with the internal organs,and plays the role of promoting qi movement,regulating water channel and distributing ministerial fire.The dysfunction of shaoyang pivot leads to the disorder of qi movement,abnormal water metabolism,and stagnation or hyperactivity of ministerial fire.Cholinergic urticaria is a special type of urticaria caused by the disorder of cholinergic nerve conduction,which has a long course of disease and is difficult to be cured.According to the clinical characteristics of the disease,Professor SUI Dao-Shun believes that the dysfunction of shaoyang pivot is the core pathogenesis of cholinergic urticaria.Emotional disorders lead to the dysfunction of pivot,and then cause the disordered flow of qi and fluid and internal disturbance of hyperactive ministerial fire,which induce the disharmony between nutritive qi and defensive qi,and the failure of being against the pathogens.Finally,wind pathogen attacks the skin and muscular striae and becomes latent,and results in cholinergic urticaria.For the treatment of cholinergic urticaria,Chaihu Guizhi Decoction can be used as the basic prescription to harmonize shaoyang,expel pathogens and release exterior.Corresponding modification of herbal medicines should be performed for various syndromes caused by the dysfunction of shaoyang pivot such as qi stagnation,dampness retention and heat stagnation during the clinical application.The prevention and treatment of cholinergic urticaria based on the theory of shaoyang as the pivot can provide thoughts for the clinical treatment of cholinergic urticaria.

OBJECTIVE To explore the effects and mechanism of Huayu qutan formula on atherosclerosis （AS） in ApoE－/－ mice. METHODS Thirty ApoE－/－ mice were randomly divided into model group， Huayu qutan formula group [20 g/（kg·d）]， rosuvastatin group [1.55 mg/（kg·d）]， with 10 mice in each group. Another 10 C57BL/6J mice were selected as normal control group. ApoE－/－ mice were given high-lipid diet for 12 weeks to induce AS model. After modeling， each group was given relevant medicine or normal saline intragastrically， once a day， for 4 consecutive weeks. After the last administration， the levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL- C）， 5，6-epoxyeicosatrienoic acid （5，　6-EET）， 8，9-EET， 11，12-EET， 14，15-EET， interleukin-1β （IL-1β） and IL-18 in serum were detected； mRNA expressions of inhibitor of nuclear factor κB （IκB）， nuclear factor κB （NF-κB）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， Caspase-1， IL-1β and IL-18 in the aortic tissue of mice were detected； protein expression levels of IκB， NF- κB， NLRP3， apoptosis-associated speck-like protein containing CARD （ASC）， Caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in the aortic tissue of mice were detected. The morphological changes of the aortic tissue were observed. RESULTS Compared with model group， the serum levels of TC， TG， LDL-C， IL-1β and IL-18， the mRNA expressions of IκB， NF-κB， NLRP3， Caspase-1， IL-1β and IL-18 in aortic tissue， and the protein expressions of IκB， NF-κB， NLRP3， ASC， Caspase-1， GSDMD， IL-1β and IL-18 were all decreased significantly in Huayu qutan formula group and rosuvastatin group （P＜0.05）， while the serum levels of 5，6-EET， 8，9-EET， 11，12-EET and 14，15-EET were increased significantly （P＜0.05）. The aortic atherosclerotic plaques were alleviated significantly. CONCLUSIONS Huayu qutan formula can play role of anti-AS through EETs-mediated pyroptosis.

Food toxicology plays a crucial role in supporting scientific and technical aspects of food safety risk assessment.However,traditional methods relying on animal testing are becoming increas-ingly inadequate for identifying and evaluating emerging foods and unknown risks.There is a strong push worldwide towards the development of new approach methodologies(NAMs)based on non-animal testing methods.Policies and regulations related to NAMs are being standardized gradually in the European Union,the United States,and China.Some progress has also been made in applying these methodologies in food toxicology research in China.For instance,within the"Food Toxicology Program"at the National Center for Food Safety Risk Assessment,high-content and high-throughput in vitro hazard identification models employing model organisms like human macrophages,hepatocytes,adipocytes,embryonic stem cells,and zebrafish,as well as Toxicological Thresholds of Concern and quantitative in vitro to in vivo extrapolation based on physiologically-based toxicokinetic models have been estab-lished and applied.Nonetheless,new toxicological hazard identification technologies still face challenges such as inadequate elucidation of toxic mechanisms,insufficient collaborative research efforts,and inef-ficient translation of these findings into practical applications.