ObjectiveTo explore the effects of angle and original moisture content on the moisture distribution， migration and contents of effective components in the drying process of sliced Salviae Miltiorrhizae Radix et Rhizoma（SMRR）. MethodsSet the slicing angles of SMRR at 30°， 45°， and 90°. Cut the fresh samples， 1/3 dehydrated samples， and 2/3 dehydrated samples， dry them in an oven at 40 ℃ and take samples at the set time points. Low-field nuclear magnetic resonance（LF-NMR） and magnetic resonance imaging（MRI） were used to analyze the changes in transverse relaxation time（T₂） of SMRR samples in 9 treatment groups at specific times， as well as the distribution and migration of water in the samples. The contents of tanshinone Ⅱ_A， tanshinone Ⅰ， cryptotanshinone， and salvianolic acid B in samples from 9 different treatment groups were determined by high performance liquid chromatography（HPLC）， and the best processing technology of SMRR was screened by combining with One-way ANOVA， Duncan multiple comparison and principal component analysis（PCA）. ResultsThe moisture content of dry basis of SMRR in each treatment group decreased with the extension of drying time. The drying rate of fresh cut group decreased slowly at first， while the drying rate of water loss group showed a trend of increasing at first and then decreasing. The internal water of SMRR could be divided into three states， including bound water， non flowing water and free water. During the drying process， the water migration law showed that the free water of fresh cut group disappeared after drying for 12 h， the content of bound water gradually decreased， and the overall fluidity deteriorated. In the water loss group， part of the free water was transformed into more cohesive and non flowing water after drying for 3 h， and the three kinds of water basically disappeared after drying for 12 h. The MRI results showed that the entire dehydration process slowly moved from the outer side to the center， and the internal water eventually dissipated. In terms of the contents of active ingredients， the order of the effect of slicing angle on the total content of active ingredients in SMRR was 30°>45°>90°. The content of tanshinones was ranked as 1/3 dehydrated group>2/3 dehydrated group>fresh cut group， and the content of salvianolic acid B was ranked as 1/3 dehydrated group>fresh cut group>2/3 dehydrated group. Combined with the results of PCA and comprehensive scoring results， the overall level of effective component content in SMRR was the highest when cut at 30° after 1/3 of water loss. ConclusionAfter comprehensive evaluation， SMRR can be sliced at 30° after 1/3 of water loss. It is not only easy to cut， but also the surface and cross-sectional colors remain basically unchanged after drying， which is similar to the color under traditional processing， and the effective ingredients are preserved the highest. This study can provide a basis for the optimization of processing technology of SMRR.

Objective To develop GTKO (α-1,3-galactosyltransferase gene-knockout, GTKO)/hCD55 (human CD55) gene-edited xenotransplant donor pigs and verify their function. Methods In this study, CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated nuclease 9), PiggyBac transposon technology and somatic cell nuclear transfer technology were used to construct GTKO/hCD55 gene-edited Diannan miniature pigs. The phenotype and function of GTKO/hCD55 pigs were analyzed by Sanger sequencing, real-time fluorescence quantitative PCR, flow cytometry, immunofluorescence, bisulfite sequencing, antigen-antibody binding assays, and complement-dependent cytotoxicity assays. Results After transfection of PX458 and PiggyBac gene editing vectors into wild-type fetal pig fibroblasts, 48 single-cell colonies were obtained through puromycin drug screening. Two single-cell colonies were selected for somatic cell nuclear transfer, resulting in two fetal pigs at 33 days of gestation. The GGTA1(α-1,3-galactosyltransferase) genotypes of fetal pig F01 were -17 bp and wild type (WT), while the GGTA1 genotypes of fetal pig F02 were -26 bp/+2 bp and -3 bp. The hCD55 mRNA expression levels of both fetal pigs were significantly higher than those of WT pigs (P＜0.01). The fetal pig F02 was selected as the donor cell source for recloning, 11 surviving piglets were obtained, all identified as GTKO/hCD55 gene-edited pigs. These pigs showed absence of α-Gal antigen expression, but weak or no expression of hCD55 was observed. Methylation analysis of the hCD55 gene's CpG island showed hypermethylation in kidney tissue lacking hCD55 expression, whereas it was not methylated or partially methylated in kidney tissue expressing hCD55. Moreover, codon optimization of the CpG island of the hCD55 gene to reduce CG content could achieve stable expression of the hCD55 gene. In addition, antigen-antibody binding experiment showed that the amount of human IgM binding to GTKO/hCD55 gene-edited pig fibroblasts was significantly lower than that of WT pigs (P＜0.01). Complement-dependent cytotoxicity experiment showed that the survival rate of fibroblasts in GTKO/hCD55 pigs was significantly higher than that in WT pigs (P＜0.01). Conclusion This study demonstrates the successful generation of GTKO/hCD55 gene-edited xenotransplant donor pigs. Methylation-induced gene silencing of the hCD55 gene can be effectively avoided by reducing the CG content of the CpG island through codon optimization. This study provides a reference for the development of xenotransplant donor pigs and guides subsequent research on xenotransplantation.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6％(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4％in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

Objective:To extract the early result of postoperative echocardiographic evaluation in patients underwent left ventricular assist device (LVAD) implantation, and to assess the efficacy of surgical treatment for end-staged heart failure.Methods:Between June 2019 and May 2023, the patients underwent left ventricular assist device implantation were enrolled in this study. Demographic baseline characteristics and perioperative echocardiographic parameters were collected and analyzed.Results:A total of 28 patients were included in the study. After LVAD implantation, the heart sizes of the patients obviously reduced and the left heart contractibility function improved. The right ventricular contractibility remained stable. The proportion of the patients with moderate to severe mitral regurgitation was significantly reduced, but patients with mild to moderate aortic insufficiency increased. No serious complications such as death, pericardial tamponade and thrombosis events were observed during the follow-up period.Conclusion:LVAD implantation improved the left cardiac function, while the right cardiac function remained stable. However, it should be paid attention that the aortic valve function was impaired after the surgery. Generally, the early results of LVAD implantation for the treatment of end-stage heart failure were satisfactory.

Objective:To explore the role and mechanism of P311 in the differentiation of mouse skin fibroblasts (Fbs) into myofibroblasts.Methods:The study was an experimental research. Six 2-day-old male C57BL/6 mouse were used to extract skin Fbs by enzymatic hydrolysis method and routinely cultured. The 1 st to 3 rd passage cells were taken and divided into empty vector group transfected with empty adenovirus and P311 group transfected with P311 high expression adenovirus, and P311+myocardin-related transcription factor A (MRTF-A) small interfering RNA (siMRTF-A) group transfected with P311 high expression adenovirus and siMRTF-A according to the random number table. After 72 h of culture, the cell proliferation vitality of cells in 3 groups was detected by cell counting kit 8, the protein expressions of MRTF-A, α-smooth muscle actin (α-SMA), and serum response factor (SRF) in cells in 3 groups were detected by Western blotting, the collagen gel contraction assay was performed and the 72 h gel contraction rates in 3 groups were calculated. The sample numbers in the above experiments were all 3. The protein expressions of MRTF-A and SRF in cells, cytoplasm, and nucleus in cells in empty vector group and P311 group were detected by Western blotting, with sample number of 4. Results:After 72 h of culture, the cell proliferation vitality of cells in empty vector group, P311 group, and P311+siMRTF-A group was similar ( P>0.05). After 72 h of culture, compared with those in empty vector group, the protein expressions of MRTF-A, α-SMA, and SRF in cells in P311 group were significantly increased ( P<0.05), while the protein expressions of MRTF-A and SRF in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). Compared with those in P311 group, the protein expressions of MRTF-A, SRF, and α-SMA in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). The 72 h gel contraction rate showing cell contractility in P311 group was (84.8±6.2)%, which was significantly higher than (27.8±2.6)% in empty vector group and (24.7±3.2)% in P311+siMRTF-A group (with P values all <0.05). The 72 h gel contraction rates in empty vector group and P311+siMRTF-A group were similar ( P>0.05). After 72 hours of culture, the protein expressions of MRTF-A (with t values of 5.86 and 3.77, respectively, P<0.05) and SRF (with t values of 3.95 and 3.97, respectively, P<0.05) in cells and cytoplasm in P311 group were significantly higher than those in empty vector group, while the protein expressions of MRTF-A and SRF in the nucleus of cells were similar between the two groups ( P>0.05). Conclusions:P311 can promote the differentiation of fibroblasts into myofibroblasts through MRTF-A, and then participate in scar formation.

Objective To assess the screening efficacy of a novel esophageal cell collector and esophageal exfoliated cell cytology examination for esophageal cancer and investigate risk factors associated with cytological examination results in the Han and Mongolian ethnic groups.Methods ①A total of 1196 high-risk individuals with esophageal cancer were selected for treatment at the Second Affiliated Hospital of Baotou Medical College.Esophageal cells were collected,and endoscopic examination and mucosal biopsy of the esophagus were performed.The pathological examination of the digestive tract endoscopic biopsy tissue was used as the gold standard to verify the diagnostic efficacy of cytological examination.① In this study,9256 Han and 572 Mongolian individuals who participated in esophageal cancer screening in the Baotou area were selected as the research subjects.General information,dietary habits,lifestyle habits,and other information of the subjects were collected through a questionnaire survey.Esophageal cells were collected using a new type of esophageal cell collector,and logistic regression analysis was used to identify the risk factors for positive cytology in Han and Mongolian populations.Results ① The novel esophageal cell collector and esophageal exfoliated cell cytology examination demonstrated excellent screening capabilities for esophageal cancer,with sensitivity(92.86％),specificity(99.58％),positive predictive value(PPV)of 72.22％,negative predictive value(NPV)of 99.92％,positive likelihood ratio(PLR)of 221.10,negative likelihood ratio(NLR)of 0.07,Youden index of 0.92,and an area under the ROC curve of 0.961(0.923-1.0).The optimal cutoff value was 2.50,yielding a sensitivity of 92.90％and specificity of 88.20％.②The cytological positivity rate among the Mongolian population(2.27％)was higher than that among the Han population(1.12％).The proportion of alcohol drinkers,those with a preference for hot and spicy foods,and those consuming pickled foods was higher in the Mongolian population than in the Han population.Logistic regression analysis revealed risk factors for the Han population:gender(OR=0.381,95％CI:0.256-0.568),age(OR=1.091,95％CI:1.067-1.116),alcohol consumption(OR=1.693,95％CI:1.150-2.492),and smoking(OR=2.127,95％CI:1.439-3.143).Risk factors for the Mongolian population were gender(OR=0.174,95％CI:0.047-0.638),age(OR=1.124,95％CI:1.052-1.200),and alcohol consumption(OR=3.945,95％CI:1.074-14.489).Conclusion ①The novel type of esophageal cell collector-esophageal exfoliative cytology examination has good screening efficacy for esophageal cancer.② Gender,age,alcohol consumption,and hot eating habits are the main risk factors for positive cytological diagnosis in the Mongolian population,while gender,age,alcohol consumption,and smoking are the main risk factors for positive cytological diagnosis in the Han population.

Approximately 50% of patients suffering from relapsed/refractory B-acute lymphoblastic leukemia (R/R B-ALL), experience relapse within one year, with around 60% of these relapses being antigen-positive, despite the transformative impact of chimeric antigen receptor (CAR) T cell therapy. The mechanisms underlying relapse are primarily associated with tumor heterogeneity, CAR-T cell dysfunction, subopimal in vivo expansion and persistence, and an inhibitory immune microenvironment. This review aims to investigate salvage strategies designed to enhance outcomes for patients undergoing relapse or disease progression following the CAR-T cell therapy. These strategies include a second CAR-T cell infusion that targets either the same antigen or an alternative target, the administration of immune checkpoint inhibitors, and the utilization of novel targeted therapies including monoclonal antibodies, antibody-conjugated drugs and small molecule compounds aimed at mitigating CD19-positive relapse or overcoming CAR-T cell resistance. Nevertheless, achieving improved long-term survival for these patients continues be challenging.

Objective To observe the effect of different concentrations of glutamine(Gln)on the radiosensitivity of colorectal cancer HT-29 cells and explore the possible mechanism.Methods According to different Gln concentrations,HT-29 cells at logarithmical growth were divided into control group(2 mmol/L,as the basal medium concentration group)and experimental groups Ⅰ,Ⅱ and Ⅲ(4,6 and 8 mmol/L).After a 2-hour pre-treatment,all groups were exposed to 8 Gy irradiation of a Co-60 radiation source.CCK-8 assay and clonal formation assay were used respectively to explore the effects of different Gln concentrations on cell viability and cell radiosensitivity after irradiation.The level of reactive oxygen species(ROS)in each group was measured in 24 h after irradiation,and the apoptotic rate was detected with flow cytometry in 48 h after irradiation.The protein expression levels of Nrf2,HO-1,and cleaved-Caspase3 were determined by Western blotting.Results In 24 h after Gln intervention,the cell viability of experimental groups Ⅱ and Ⅲof non-irradiated HT-29 cells was significantly higher than that of the control group and of experimental group Ⅰ(P＜0.05).In 24 h after radiation,the cell viability of each experimental group was significantly higher than that of the control group(P＜0.05).In 14 d after radiation,there were more clone formation in each experimental group than the control group(P＜0.05).The ROS level was significantly lower in each experimental group than the control group in 24 h after radiation(P＜0.05).After 48 h of radiation,the apoptotic rate was notably lower in each experimental group than the control group(P＜0.05).The expression level of Nrf2 in the experimental group Ⅰ was higher than that of the control group(P＜0.05),those of Nrf2 and HO-1 in the experimental groups Ⅱ and Ⅲ were higher than those of the control group and experimental group Ⅰ(P＜0.05).While the expression of cleaved-Caspase3 in the experimental groups Ⅱ and Ⅲ was lower than the control group and experimental group Ⅰ(P＜0.05),and it in the experimental group Ⅲ was lower than that of experimental group Ⅱ(P＜0.05).Conclusion Gln can significantly reduce the radiosensitivity of HT-29 cells,which is associated with its reducing oxidative stress damage and reducing cell apoptosis.Our results suggest that Gln might be detrimental to radiation therapy in patients with colorectal cancer.