ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

OBJECTIVES: To analyze MYO1B expression in gastric cancer, its association with long-term prognosis and its role in regulating biological behaviors of gastric cancer cells. METHODS: We analyzed MYO1B expression in gastric cancer and its correlation with tumor grade, tumor stage, and patient survival using the Cancer Public Database. We also examined MYO1B expression with immunohistochemistry in gastric cancer and paired adjacent tissues from 105 patients receiving radical surgery and analyzed its correlation with cancer progression and postoperative 5-year survival of the patients. GO and KEGG enrichment analyses were used to explore the biological functions of MYO1B and the key pathways. In cultured gastric cancer cells, we examined the changes in cell proliferation, migration and invasion following MYO1B overexpression and knockdown. RESULTS: Data from the Cancer Public Database showed that MYO1B expression was significantly higher in gastric cancer tissues than in normal tissues with strong correlations with tumor grade, stage and patient prognosis (P<0.05). In the clinical tissue samples, MYO1B was significantly overexpressed in gastric cancer tissues in positive correlation with Ki67 expression (r=0.689, P<0.05) and the parameters indicative of gastric cancer progression (CEA ≥5 μg/L, CA19-9 ≥37 kU/L, G3-4, T3-4, and N2-3) (P<0.05). Kaplan-Meier analysis and multivariate Cox regression analysis suggested that high MYO1B expression was associated with decreased postoperative 5-year survival and was an independent risk factor (HR: 3.522, 95%CI: 1.783-6.985, P<0.05). MYO1B expression level was a strong predictor of postoperative survival (cut-off value: 3.11, AUC: 0.753, P<0.05). GO and KEGG analyses suggested that MYO1B may regulate cell migration and the mTOR signaling pathway. In cultured gastric cancer cells, MYO1B overexpression significantly enhanced cell proliferation, migration, and invasion and promoted the phosphorylation of Akt and mTOR. CONCLUSIONS High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is correlated with poor patient prognosis.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Prognosis ; Cell Movement ; Myosin Type I/genetics* ; Neoplasm Invasiveness ; Cell Line, Tumor ; Female ; Male

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Objective:To investigate the feasibility and safety of implementing a domestic vehicle-mounted remote mobile robotic surgical system in thyroid surgery applications, integrated with 5G communication technology.Methods:Using the main system located on the vehicle-mounted mobile robot operating platform of the 960th Hospital of PLA Joint Logistics Support Force and the slave system of Weifang Traditional Chinese Hospital, the remote radical thyroidectomy 5G communication technology, and analyze the clinical and information transmission data of two female patients who underwent remote mobile robot thyroid cancer surgery on October 21, 2024 at Weifang Traditional Chinese Medicine Hospital.Results:The remote radical thyroidectomy was conducted by the robosurgeons utilizing a vehicle-mounted mobile robotic surgical system, and the procedure was successfully completed without necessitating intermediate open surgery. The operation durations for patient 1 and patient 2 were 135 minutes and 108 minutes, respectively, with 7 and 13 lymph nodes dissected, respectively. The average delay in surgical data transmission was recorded at 61.9 milliseconds, with no instances of signal interruption or frame loss. The procedure proceeded smoothly, without any jamming, and the audio and video transmissions were consistently clear. Follow up for 21 days after surgery showed no complications such as hoarseness, skin damage, or lymphatic fistula.Conclusion:The implementation of a vehicle-mounted remote mobile robotic surgery system for thyroid surgery has demonstrated safety and feasibility. Furthermore, the utilization of the 5G network offers rapid data transmission and minimal latency, closely approximating the therapeutic efficacy of traditional robotic thyroidectomy.

ObjectiveTo explore the metabolic changes during the development of Tupaia belangeri breast tumors, to investigate the close relationship between the changes of serum metabolic substances and the occurrence and progression of tumors, and to screen for biomarkers reflecting the progression of breast tumors. MethodsBreast tumors in Tupaia belangeri were induced by orally administering 7,12-dimethylbenzoanthracene (DMBA) three times, with a 15-day interval between each administration, along with a high-fat and high-sugar diet. The DMBA-induced breast cancer group and the DMBA-inducedwithout breast cancer group were compared with the control group. Untargeted determination of serum metabolites was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) in DMBA-induced Tupaia belangeri with breast cancer, DMBA-induced without breast cancer and the control group. Multidimensional statistical analysis including unsupervised principal component analysis (PCA), and orthogonal partial least squares analysis (OPLS-DA) were conducted. Furthermore, t-test was used for intergroup differential comparison. Differential metabolites were screened under VIP>1 and P<0.05 conditions, and significantly changing differential metabolites were identified using the HMDB online database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was utilized to enrich metabolic-related gene regulatory pathways. ResultsThe incidence of breast tumors was 40% in DMBA-induced Tupaia belangeri. Compared with the control group, 30 metabolic differential products were detected in the serum of the group with breast cancer, with 18 down-regulated and 12 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in four metabolic pathways: glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism. Compared with the group without breast cancer, 18 metabolic differential products were detected, with 7 down-regulated and 11 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in the citric acid cycle and glutamate metabolism. Compared with the control group, 31 metabolic differential products were detected in the serum of the groups without breast cancer, with 14 down-regulated and 17 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in three metabolic pathways: glutamate metabolism, glyceride metabolism, and citric acid cycle. ConclusionMetabolomics analysis can reveal the characteristics of changes in metabolites in the serum of breast tumors. The results suggest that glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism pathways are associated with the occurrence and development of DMBA-induced breast tumors in Tupaia belangeri. It provides a foundation for further research into the biological mechanism of breast cancer.

Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

Objective To detect the expression of translationally-controlled tumor protein 1(TPT1)in renal cell carcinoma(RCC)and to explore its role in RCC.Methods Microarray dataset GSE15641(including 23 normal kidney tissue samples and 32 RCC tissue samples)was downloaded from the Gene Expression Omnibus,and differentially expressed genes between RCC tissue and normal kidney tissue were screened using R 4.3.0 software.The TPT1 expression in RCC tissue and adjacent non-tumor tissue of 90 patients diagnosed and treated at Affiliated Hospital of Nantong University,as well as in human RCC cells(769-P,786-O,ACHN,and Caki-1)and human embryonic kidney 293 cell(HEK293)was detected by quantitative polymerase chain reaction(qPCR)and Western blotting.The relationship between TPT1 expression and clinical pathological characteristics of RCC patients was analyzed by χ2 test.The clinical data of 522 RCC patients were derived from The Cancer Genome Atlas,and the correlation between TPT1 expression and prognosis of RCC patients was analyzed by receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.After in vitro transfection of TPT1 small interfering RNA(siRNA)and its negative control(NC)into 786-O and Caki-1 cells,the TPT1 expression was detected by qPCR and Western blotting;the proliferation,migration,and invasion were detected by cell counting kit 8 assay,scratch assay,and Transwell assay,respectively;and the expression of apoptosis-related proteins was detected by Western blotting.Results TPT1 expression was significantly upregulated in the RCC tissue and cells compared with the normal kidney tissue and HEK293 cells(all P＜0.05).The RCC patients with low TPT1 expression levels had significantly smaller tumor size and lower metastasis rate than those with high TPT1 expression levels(both P＜0.05).The ROC curve analysis results indicated that TPT1 had high diagnostic value for RCC(area under curve was 0.856 9,95%confidence interval was 0.804 5-0.909 3,P＜0.001).The Kaplan-Meier survival analysis results showed that the overall survival of RCC patients in the low TPT1 expression group was significantly longer than that in the high TPT1 expression group(P=0.018 4).In the cell experiment,compared with the siRNA NC group,the proliferation activity,scratch healing rate,and invading transmembrane cell number of 786-O and Caki-1 cells were significantly decreased after transfection with TPT1 siRNA(all P＜0.01);the expression levels of B-lymphoma gene 2(Bcl-2)and matrix metalloproteinase-9 were significantly decreased,while the expression of Bcl-2 associated X protein was significantly increased(all P＜0.05).Conclusion TPT1 is involved in the progression of RCC and may be a potential therapeutic target for RCC.

Objective To explore the impact of clinical treatment decisions on the long-term survival of different molecular subtypes of locally advanced breast cancer(LABC),and to promote the development of more effective and individualized treatment regimens for LABC.Methods The cases of LABC diagnosed by pathology from 2010 to 2015 were searched in the database.Breast cancer-specific survival(BCSS)and overall survival(OS)were estimated by plotting Kaplan-Meier curves.The log rank test(Mantel-Cox)was used to analyze the difference between the groups,and the benefit population of LABC was determined after for age,TNM stage,grade,treatment methods.Results The 5-year OS and BCSS were 77.43％and 84.34％in breast-conserving,and 68.03％and 76.90％in mastectomy,respectively.The 5-year OS and BCSS of Luminal A LABC were 79.91％and 87.23％in breast-conserving,and 71.78％and 81.16％in mastectomy,respectively.The 5-year OS and BCSS of Luminal B LABC were 79.30％and 83.14％in breast-conserving,and were 70.37％and 76.92％in mastectomy,respectively.The 5-year OS and BCSS of triple-negative LABC were 60.77％and 68.13％in breast-conserving,and those of mastectomy were 47.13％and 55.94％,respectively.The 5-year OS and BCSS of HER2 positive were 75.42％,82.05％in breast-conserving,and were 67.05％and 75.01％in mastectomy,respectively;The 5-year OS and BCSS of triple-positive LABC were 86.12％and 91.63％in breast-conserving,and 74.54％and 82.56％in mastectomy,respectively.The 5-year OS and BCSS of well differentiated and N0 triple-positive LABC patients with chemotherapy were 88.24％and 76.91％,and those of patients without chmotherapy were 88.24％and 90.91％,respectively(BCSS:P=0.812;OS:P=0.311).Conclusion In the selective population,OS and BCSS of patients with LABC undergoing breast conserving surgery were significantly better than those of mastectomy.When OS and BCSS were compared for different molecular types and stages of LABC,breast-conserving surgery was still superior to total mastectomy.LABC could be considered for highly differentiated,N0 stage Triple positive without chemotherapy.

Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.