Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Objective To explore the effects and mechanisms of Sanzi Sijun Formula(SSF)in non-alcoholic fatty liver disease(NAFLD)through network pharmacology,molecular docking and molecular dynamics simulation;To carry out experimental validation in vivo and in vitro.Methods The active components and target genes of SSF were screened using TCMSP,TCMIP and TCMIO databases.NAFLD-related targets were screened using the GeneCards database,and the intersection targets were obtained to construct a protein-protein interaction network and screen for core targets.The intersection targets were imported into the DAVID database for GO and KEGG enrichment analysis.Molecular docking was performed using AutoDock Vina software between the key active components of SSF and core targets,and molecular dynamics simulations were conducted using Gromacs 2022 for 100 ns.C57BL/6J mice NAFLD model was established by diet induction.SSF was administered by gavage for 8 weeks.Liver histopathological changes and the levels of non-esterified fatty acids(NEFA)were detected.In vitro NAFLD model was established by inducing AML12 cells with palmitic acid(PA)for 24 hours.SSF-containing serum was added to incubate simultaneously.The lipid accumulation and cell viability were detected.The core targets of SSF intervention in the in vitro and in vivo NAFLD models were verified by RT-qPCR and Western blot.Results Network pharmacological analysis identified 75 active components in SSF and revealed 179 shared targets between these components and NAFLD.Ten main active components including arachidonate,12-senecioyl-2E,8E,10E-atractylodin,cerebrosterol,glycyrrhizol B and sinapic acid,etc.as well as 8 core targets were identified.GO enrichment analysis of targets mainly involved protein phosphorylation,inflammatory response,and apoptosis,while the KEGG enrichment analysis mainly included AGE-RAGE,TNF,AMPK,PPAR and NF-κB signaling pathways.Molecular docking demonstrated that the major active components of SSF exhibited favorable binding affinity and stability with the core targets.Molecular dynamics simulation confirmed the stability of the complex of glyasperin B with AKT1,SIRT1,STAT3,PPARG,and TNF.SSF alleviated the pathological damage of liver tissues in mice NAFLD model,reduced NAS score and NEFA levels in liver tissues(P<0.05).Additionally,SSF reversed lipid accumulation and decreased cell viability of PA-induced AML12 cells(P<0.01).Further in vivo and in vitro experiments demonstrated that SSF significantly reversed the elevated mRNA levels of TNF-α,IL-6,IL-1β and PPARγ and protein expression of STAT3(P<0.05,P<0.01)in NAFLD models,up-regulated the protein levels of SIRT1 and p-Akt/Akt(P<0.05,P<0.01).Conclusion SSF can improve NAFLD of both in vitro and in vivo models.The regulation of multiple targets,such as AKT,SIRT1,STAT3 and PPARG,by its multiple active components,and adjustment of multiple approaches,such as lipid metabolism disorder,inflammatory responses,are involved in the potential underlying mechanisms.

Objective To explore the effects and mechanisms of Sanzi Sijun Formula(SSF)in non-alcoholic fatty liver disease(NAFLD)through network pharmacology,molecular docking and molecular dynamics simulation;To carry out experimental validation in vivo and in vitro.Methods The active components and target genes of SSF were screened using TCMSP,TCMIP and TCMIO databases.NAFLD-related targets were screened using the GeneCards database,and the intersection targets were obtained to construct a protein-protein interaction network and screen for core targets.The intersection targets were imported into the DAVID database for GO and KEGG enrichment analysis.Molecular docking was performed using AutoDock Vina software between the key active components of SSF and core targets,and molecular dynamics simulations were conducted using Gromacs 2022 for 100 ns.C57BL/6J mice NAFLD model was established by diet induction.SSF was administered by gavage for 8 weeks.Liver histopathological changes and the levels of non-esterified fatty acids(NEFA)were detected.In vitro NAFLD model was established by inducing AML12 cells with palmitic acid(PA)for 24 hours.SSF-containing serum was added to incubate simultaneously.The lipid accumulation and cell viability were detected.The core targets of SSF intervention in the in vitro and in vivo NAFLD models were verified by RT-qPCR and Western blot.Results Network pharmacological analysis identified 75 active components in SSF and revealed 179 shared targets between these components and NAFLD.Ten main active components including arachidonate,12-senecioyl-2E,8E,10E-atractylodin,cerebrosterol,glycyrrhizol B and sinapic acid,etc.as well as 8 core targets were identified.GO enrichment analysis of targets mainly involved protein phosphorylation,inflammatory response,and apoptosis,while the KEGG enrichment analysis mainly included AGE-RAGE,TNF,AMPK,PPAR and NF-κB signaling pathways.Molecular docking demonstrated that the major active components of SSF exhibited favorable binding affinity and stability with the core targets.Molecular dynamics simulation confirmed the stability of the complex of glyasperin B with AKT1,SIRT1,STAT3,PPARG,and TNF.SSF alleviated the pathological damage of liver tissues in mice NAFLD model,reduced NAS score and NEFA levels in liver tissues(P<0.05).Additionally,SSF reversed lipid accumulation and decreased cell viability of PA-induced AML12 cells(P<0.01).Further in vivo and in vitro experiments demonstrated that SSF significantly reversed the elevated mRNA levels of TNF-α,IL-6,IL-1β and PPARγ and protein expression of STAT3(P<0.05,P<0.01)in NAFLD models,up-regulated the protein levels of SIRT1 and p-Akt/Akt(P<0.05,P<0.01).Conclusion SSF can improve NAFLD of both in vitro and in vivo models.The regulation of multiple targets,such as AKT,SIRT1,STAT3 and PPARG,by its multiple active components,and adjustment of multiple approaches,such as lipid metabolism disorder,inflammatory responses,are involved in the potential underlying mechanisms.

BACKGROUND/AIMS: The Rome III criteria separated chronic constipation into functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C), but some researchers questioned the partitioning and treated both as distinct parts of a continuum. The study aims to explore the similarity and diversity of brain white matter between FC and IBS-C. METHODS: The voxel-wise analysis of the diffusion parameters was used to quantify the white matter changes of female brains in 18 FC patients and 20 IBS-C patients compared with a comparison group with 19 healthy controls by tract-based spatial statistics. The correlations between diffusive parameters and clinical symptoms were evaluated using a Pearson’s correlation. RESULTS: In comparison to healthy controls, FC patients showed a decrease of fractional anisotropy (FA) and an increase of radial diffusivity (RD) in multiple major fibers encompassing the corpus callosum (CC, P = 0.001 at peak), external capsule (P = 0.002 at peak), corona radiata (CR, P = 0.001 at peak), and superior longitudinal fasciculus (SLF, P = 0.002 at peak). In contrast, IBS-C patients showed FA and RD aberrations in the CC (P = 0.048 at peak). Moreover, the direct comparison between FC and IBS-C showed only RD differences in the CR and SLF. In addition, FA and RD in the CC were significantly associated with abdominal pain for all patients, whereas FA in CR (P = 0.016) and SLF (P = 0.040) were significantly associated with the length of time per attempt and incomplete evacuation separately for FC patients. CONCLUSION: These results may improve our understanding of the pathophysiological mechanisms underlying different types of constipation.
Abdominal Pain ; Anisotropy ; Brain ; Constipation ; Corpus Callosum ; Diffusion ; Diffusion Tensor Imaging ; External Capsule ; Female ; Humans ; Irritable Bowel Syndrome ; White Matter

ObjectiveTo investigate the prevalence of syphilis among outpatients in sexually transmitted disease (STD) clinics in Guangxi Zhnang Autonomous Region,and to assess the socioeconomic and behavioral factors associated with the infection.MethodsThe outpatients to 14 STD clinics in 8 cities of Guangxi Zhnang Autonomous Region were investigated with questionnaires by their doctors at the first visit.Venous blood samples were obtained from these outpatients and subjected to toludine red unheated serum test (TRUST) to screen for syphilis.Treponema pollidum particle agglutination (TPPA) was performed for TRUSTpositive samples.The epidemiological data were collected by using EpiData software,statistically analyzed by using SPSS13.0 software package.ResultsA total of 10 930 STD outpatients were recruited in the study,and 1297 samples were confirmed to be both TRUST and TPPA positive.The prevalence of syphilis was 11.9％ in all of the outpatients,14.3％ in female outpatients and 10.3％ in male outpatients,13.3％ in the outpatients of Zhuang nationality,and 11.4％ in those of Han nationalily.Multivariate analysis showed that syphilis was independently related to female sex[odds ratio(OR) 2.23,95％ confidence interval(CI) 1.69 - 3.00,P＜0.01 ],low educaiion level (middle school:OR 1.70,95％ CI 1.11 - 2.62,P ＜ 0.05; primary school or illiteracy,OR 1.98,95％ CI 1.13 - 3.46,P＜0.05),annual income of more than 30000 Yuan (OR 1.91,95％ CI 1.18 -3.10,P ＜ 0.01 ),commercial sex workers or having multiple sexual partners(OR 1.54,95％ CI 1.16 - 2.06,P ＜0.01 ).ConclusionsSyphilis serology should be the routine test in STD clinical settings in Guangxi region,and the intervention should be enhanced to control the prevalence of syphilis in high-risk populations.

OBJECTIVE: To evaluate the feasibility of surface tractotomy of trigeminal nerve sensory root (STS) for the treatment of trigeminal neuralgia (TN). METHOD: Seven patients with TN were operated on using the STS. The six patients were followed up for 4.8-9.8 years. The trigeminal nerve root (TNR) obtained from 30 cadavers were performed microanatomical research using paraffin embedding and hematoxylin-eosin staining technique. RESULT: Clinically, the patients' symptoms, such as face ache, disappeared after the surface nerve fiber bundles of trigeminal nerve sensory root (TNSR) were cut off. Only one patient died of brainstem bleeding on postoperative day 18. Histological examination: The common type of sensory root fibers were arranged parallel for 3-6 mm at its exit of brainstem, and then the glial myelin transformed to Schwann cells. The axon bifurcated from outer layer to middle region, and gradually formed the tiny nerve fiber bundles in the surface layer and the giant nerve fiber bundles in the center of the root. CONCLUSION TN can be radical cured by STS without lesioning of nerve functions. Therefore,this new approach is an effective, advanced surgical technique for TN treatment.
Aged ; Denervation ; methods ; Female ; Humans ; Male ; Middle Aged ; Trigeminal Nerve ; surgery ; Trigeminal Neuralgia ; surgery

BACKGROUND: Eggembryosin is characterized by tonifying kidney and vital essence, invigorating qi and spleen, replenishing and activating blood, beautifying and nourishing face, and improving constitution of whole organism.OBJECTIVE: To observe the influence of eggembryosin on aging index,quantity of hemocytes and quality of immune organs of animal models, and analyze its effect on cosmetology, anti-senility and immunoloregulation.DESIGN: Randomized controlled observation.SETTING: Department of Pharmacology, Xinxiang Medical College.MATERIALS: The experiment was carried out in the Department of Pharmacology of Xinxiang Medical College between April 1998 and September 2002. A total of 80 Kunming mice of both sexes were selected in this study.METHODS: ① Effect of eggembryosin on activity of superoxide dismutase (SOD) in serum, content of malondialdehyde (MDA), lipofuscin and hydroxyproline respectively in serum, liver and tendon of tail of aging mice: Thirty mice were divided into 3 groups according to randomly lined table, including eggembryosin group, D-galactose model group and normal control group with 10 in each group. The former two groups were injected with D-galactose to copy aging models, and eggembryosin group were perfused with eggembryosin to measure activity of SOD in serum, content of MDA, lipofuscin (aging index) and hydroxyproline (elasric index of skin) respectively in serum, liver and tendon of tail. ② Effect of eggembryosin on mass of immune organs of mice with low immunological function: Thirty mice were selected and divided as the same way mentioned above. Mice in eggembryosin group were perfused with eggembryosin. In addition, those in eggembryosin group and cyclophosphamide (CAP) group were peritoneally injected with CAP to copy immunosuppression models and calculate index of thymus (spleen) (mg/g) = weight of thymus (spleen)/body. ③ Effect of eggembryosin on quantities of erythrocytes and hemoglobin of mice with blood deficiency: Twenty mice were divided into 2 groups according to randomly lined table, including eggembryosin group and normal control group with 10 in each group. Values of erythrocytes and hemoglobins of mice were measured before administration. Models in types of blood-deficiency blood-loss were copied with tail xsanguinations, and then, mice were perfused with eggembryosin and saline, respectively. Blood of mice were collected from their tails to measure values of erythrocytes and hemoglobin.MAIN OUTCOME MEASURES: Activity of superoxide dismutase (SOD) in serum, content of malondialdehyde (MDA), lipofuscin and hydroxyproline respectively in serum, liver and tendon of tail of aging mice, index of thymus, and spleen, contents of blood erythrocytes and hemoglobins.RESULTS: A total of 80 mice were involved in the final analysis without any loss. ① Activity of SOD in serum and contents of hydroxyproline in tendon of tail of mice in eggembryosin group were significantly higher than those of mice in D-galactose model group (P ＜ 0.01); content of MDA in serum and content of lipofuscin in liver of mice in eggembryosin group were significantly lower than those of mice in D-galactose model group (P＜ 0.01). ② Indexes of thymus and spleen of mice in eggembryosin group were higher than those of mice in CAP group (P ＜ 0.05-0.01). ③ Increasing values of blood erythrocytes and hemoglobin of mice in eggembryosin group were significantly higher than those of mice in normal control group (P ＜ 0.01).CONCLUSION: Eggembryosin taken orally can improveanti-oxidation of organism and elasticity of skin, increase quality of immune organs damaged by CAP and immunological function, and nourish the blood.