Objective: To establish and identify hepatocyte-specific transmembrane protein 121 ( Tmem121 ) knockout mice． Methods: The hepatocyte-specific Tmem121 knockout mice ( Tmem121flox / flox / Cre，Tmem121ΔHep) were obtained by crossbreeding of Tmem121flox / + / Cre and Tmem121flox / flox mice，which were generated using the CRISPR / Cas9 and Cre / Loxp systems．The genotype was verified by PCR using genomic DNA extracted from mouse tails as template．The growth，reproduction and organ development of both control and knockout mice were ob- served and analyzed．PCR and Western blot methods were performed to assess the knockout efficiency of Tmem121 in mouse primary hepatocytes．CellMaskTM Deep Red plasma membrane staining was employed to compare the mor- phological differences in primary hepatocytes between control and knockout mice． Results: Tmem121flox / flox / Cre mice were successfully obtained according to genotype identification analysis，and there were no significant differ- ences between control and knockout mice in body mass，reproductive ability，growth and development of liver．The specific knockout of Tmem121 gene in primary hepatocytes did not significantly affect the morphological structure or pathological characteristics of liver tissue．However，compared to the control group，the levels of Tmem121 mRNA and protein in the primary hepatocytes of the knockout group were significantly reduced ( P ＜0. 01) ．CellMaskTM Deep Red plasma membrane staining indicated that the proportion of binucleated hepatocytes in Tmem121-deficient mice significantly increased ( P＜0. 05) ，while the cell area was significantly reduced ( P＜0. 001) ． Conclusion Hepatocyte-specific Tmem121 knockout mice are successfully constructed，which provides an animal model for further exploration of the function and mechanism of Tmem121 gene in liver diseases．

Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.

Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.

ObjectiveBased on the experience of traditional quality evaluation， the quality of Atractylodis Macrocephalae Rhizoma（AMR） with different production methods such as direct seeding， transplanting after seedling raising， topping and non-topping， and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining， and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides， oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography（UPLC）， and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）. ResultIn terms of traits， the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck， strong sweetness and clear aroma" recorded in ancient materia medica， followed by the 3-year-old AMR with topping after transplanting， while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect， the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang， the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition， the contents of 70% ethanol extract， fructose， glucose， sucrose， 1-kestose， atractylenolide Ⅰ， chlorogenic acid， neochlorogenic acid， cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples（P<0.05）. The contents of cellulose， 70% ethanol extract， sucrose， atractylenolide Ⅰ， atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate（P<0.05）， while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting， direct seeding and without topping（P<0.05）. ConclusionUnder the current mainstream production mode， too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield， but the accumulation of sweet substances， fragrant substances and fiber substances is insufficient， which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it， it is suggested to revise the quality standard of AMR， supplement the quantitative analysis of secondary metabolites， and strengthen the production of imitation wild AMR.

A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg^-1） and total alkaloids of C. saxicola group（210 mg·kg^-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（t_max） and half-life（t_1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC_0-∞） of tetrahydropalmatine was the highest and the t_1/2 was the shortest， and the AUC_0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.

【Objective】 To investigate the prevalence of QTc prolongation and the risk factors in hospitalized breast cancer patients. 【Methods】 A total of 296 patients with pathologically diagnosed breast cancer admitted to The First Affiliated Hospital of Xi’an Jiaotong University in 2018 were retrospectively enrolled. The patients’ baseline data， 12-lead ECG， the prevalence of QTc （QTc max） prolongation and its risk factors were analyzed by the multivariate logistic regression. 【Results】 The prevalence of QTc prolongation in the hospitalized breast cancer patients was 13%； multivariate logistic regression analysis showed that increased heart rate （OR=1.04， P<0.05）， combined hypertension （OR=6.48， P<0.05）， and anthracycline administration （OR=3.96， P<0.05） were the risk factors of the prolongation of QTc interval in the breast cancer patients （P<0.05）. 【Conclusion】 The prevalence of prolonged QTc interval in the hospitalized breast cancer patients is increased， which may be due to the increased heart rate， hypertension， and the administration of anthracycline drugs in these patients.

In view of the shortage of research on the seismic performance of medical imaging equipment, this paper investigates and summarizes the seismic regulatory requirements and seismic tests of medical imaging equipment, and focuses on the parameter selection, detection steps, result evaluation and detection equipment requirements of seismic detection of medical imaging equipment. The seismic test data of medical imaging equipment with various installation modes are analyzed, and the seismic performance of medical imaging equipment is analyzed and summarized.
Diagnostic Imaging

Objective To observe the effect of Shenmai injection combined with enteral nutrition (EN) on immune function in patients with severe cardiac insufficiency. Methods Fifty-seven patients with severe cardiac insufficiency admitted to the Department of Critical Care Medicine of Taizhou Hospital of Zhejiang Province from June 2015 to June 2018 were divided into an EN group (31 cases) and an EN group combined with Shenmai injection group (26 cases). The EN group was given EN on the basis of routine western medicine treatment, while in the EN combined with Shenmai injection group was treated additionally by intravenous drip of Shenmai injection 100 mL/d on the basis of above EN group treatment. The efficacies of the two groups were evaluated after consecutive 7-day treatment in the two groups. The changes in levels of subsets of T-lymphocytes (CD3+, CD4+, CD8+, CD4+/CD8+) and immunosuppressive cells CD14+ monocyte human leukocyte antigen DR (HLA-DR) were observed before and after treatment. Results After treatment, the levels of T-cell subsets CD3+, CD4+, CD4+/CD8+ and CD14+ monocytes HLA-DR in the peripheral blood of the two groups were significantly higher than those before treatment [CD3+: EN group was 0.539±0.126 vs. 0.379±0.093,Shenmai injection group was 0.652±0.185 vs. 0.393±0.091; CD4+: EN group was 0.402±0.121 vs. 0.275±0.066,Shenmai injection group was 0.524±0.168 vs. 0.281±0.077; CD4+/CD8+:EN group was 1.83±0.70 vs. 1.11±0.70,Shenmai injection group was 2.81±0.91 vs. 1.19±0.58; CD14+HLA-DR:EN group was (43.3±7.1)% vs. (35.4±5.7)%,Shenmai injection group was (54.9±6.2)% vs. (36.1±8.3)%]; After treatment, CD8+ in EN group decreased (0.223±0.052 vs. 0.253±0.081), while CD8+ in shenmai injection group increased (0.288±0.051 vs. 0.259±0.078), and the increase degrees of the above-mentioned indexes in EN combined with Shenmai injection group were more obvious than those in the EN group after treatment [CD3+: 0.652±0.185 vs. 0.539±0.126, CD4+: 0.524±0.168 vs. 0.402±0.121, CD8+: 0.288±0.051 vs. 0.223±0.052, CD4+/CD8+: 2.81±0.91 vs. 1.83±0.70, CD14+HLA-DR: (54.9±6.2)%, (43.3±7.1)%, all P < 0.05]. Conclusion The combined use of Shenmai injection and early EN can improve the immune function of T-lymphocytes in patients with severe cardiac insufficiency. The mechanism may be related to the enhancement of the activation of T lymphocytes and promotion of the CD14+ monocytes increase and immune function.