1.Differences in HER2-0 and HER2-low Breast Cancer: Androgen Receptor and Programmed Death Ligand 1 as Predictive Factors
Xiaoqi ZHANG ; Ciqiu YANG ; Yitian CHEN ; Junsheng ZHANG ; Peiyong LI ; Na HUANG ; Yilin CHEN ; Minting LIANG ; Weiming LV ; Zhongyu YUAN ; Jie LI ; Kun WANG
Journal of Breast Cancer 2025;28(1):23-36
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.
2.Differences in HER2-0 and HER2-low Breast Cancer: Androgen Receptor and Programmed Death Ligand 1 as Predictive Factors
Xiaoqi ZHANG ; Ciqiu YANG ; Yitian CHEN ; Junsheng ZHANG ; Peiyong LI ; Na HUANG ; Yilin CHEN ; Minting LIANG ; Weiming LV ; Zhongyu YUAN ; Jie LI ; Kun WANG
Journal of Breast Cancer 2025;28(1):23-36
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.
3.Differences in HER2-0 and HER2-low Breast Cancer: Androgen Receptor and Programmed Death Ligand 1 as Predictive Factors
Xiaoqi ZHANG ; Ciqiu YANG ; Yitian CHEN ; Junsheng ZHANG ; Peiyong LI ; Na HUANG ; Yilin CHEN ; Minting LIANG ; Weiming LV ; Zhongyu YUAN ; Jie LI ; Kun WANG
Journal of Breast Cancer 2025;28(1):23-36
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.
4.Tissue-resident peripheral helper T cells foster hepatocellular carcinoma immune evasion by promoting regulatory B-cell expansion.
Haoyuan YU ; Mengchen SHI ; Xuejiao LI ; Zhixing LIANG ; Kun LI ; Yongwei HU ; Siqi LI ; Mingshen ZHANG ; Yang YANG ; Yang LI ; Linsen YE
Chinese Medical Journal 2025;138(17):2148-2158
BACKGROUND:
Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown.
METHODS:
Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays.
RESULTS:
T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression.
CONCLUSION
Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism*
;
Liver Neoplasms/metabolism*
;
Humans
;
T-Lymphocytes, Helper-Inducer/metabolism*
;
Animals
;
Mice
;
Male
;
Female
;
Mice, Inbred C57BL
;
Middle Aged
;
B-Lymphocytes, Regulatory/metabolism*
;
Flow Cytometry
;
Interleukin-21
;
Aged
;
Chemokine CXCL13/metabolism*
5.Application of Assessment Scales in Palliative Care for Glioma: A Systematic Review.
Zhi-Yuan XIAO ; Tian-Rui YANG ; Ya-Ning CAO ; Wen-Lin CHEN ; Jun-Lin LI ; Ting-Yu LIANG ; Ya-Ning WANG ; Yue-Kun WANG ; Xiao-Peng GUO ; Yi ZHANG ; Yu WANG ; Xiao-Hong NING ; Wen-Bin MA
Chinese Medical Sciences Journal 2025;40(3):211-218
BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans
;
Glioma/psychology*
;
Palliative Care/methods*
;
Quality of Life
;
Psychometrics
;
Brain Neoplasms/psychology*
6.The observational chart for traumatic limb swelling enhances diagnostic accuracy for osteofascial compartment syndrome.
Zhi-Wei YANG ; Zhao-Di WANG ; Jun-Sheng YANG ; Liang-Cheng TONG ; Lei ZHAO ; Wei DAI ; Kun PANG ; Ying LI
Chinese Journal of Traumatology 2025;28(6):454-461
PURPOSE:
To evaluate the diagnostic accuracy of the observational chart for traumatic limb swelling (OCTLS) for osteofascial compartment syndrome (OCS).
METHODS:
This was a descriptive-longitudinal study. Data of 316 patients who underwent surgical treatment for tibial fractures in our department from January 2015 to December 2023 were collected. Patients with Gustilo type II or higher open fractures, vascular injury, or bilateral fractures were excluded from the study. Two groups of double-blinded investigators independently assessed patients for the presence of OCS using 2 distinct diagnostic methods. Three senior orthopedic trauma surgeons evaluated patients with post-fracture calf swelling for OCS and the need for fasciotomy based on clinical signs and their extensive clinical experience. Subsequently, fasciotomy was performed according to their judgment, followed by postoperative examination of muscle and soft tissue conditions. Additionally, a follow-up evaluation was conducted to assess for complications such as ischemic muscle contracture. Another 3 trained researchers used OCTLS to grade swelling severity and determine the need for fasciotomy. The final diagnostic gold standard of OCS was determined by referring to whether there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively, and neurological abnormality or contracture at the last follow-up. The results of the 2 diagnostic methods were compared with the final diagnostic result. Kappa consistency test, paired χ2 test (McNemar test), and receiver operating characteristic curve were used to evaluate the diagnostic efficacy of the 2 diagnostic methods.
RESULTS:
Of the 316 patients, 211 were finally included in the study, including 160 males and 51 females, with an average follow-up time of (14.5 ± 2.7) months. Among the 211 patients with tibial fracture-associated swelling, 42 were definitively diagnosed with OCS. Based on clinical symptoms and signs judgment, among the 65 fasciotomy patients, 38 were confirmed as correct, while among the 146 non-fasciotomy patients, 4 developed ischemic muscle contractures. Based on the OCTLS for assessment, fasciotomy was correctly recommended in 36 out of 43 cases, while 6 out of 168 non-fasciotomy patients developed OCS. Compared to the use of the gold standard, clinical signs judgment showed moderate consistency (McNemar's test p < 0.001, Kappa = 0.618, p < 0.001), whereas OCTLS demonstrated strong agreement (McNemar's test p = 1.000, Kappa = 0.808, p < 0.001). Receiver operating characteristic analysis revealed higher diagnostic accuracy for OCTLS (area under curve = 0.908, 95% CI: 0.843 - 0.972) compared to clinical signs judgment (area under curve = 0.872, 95% CI: 0.812 - 0.933). OCTLS achieved superior accuracy (93.8% vs. 85.3%, χ2 = 8.221, p < 0.001) and a lower fasciotomy rate (20.4% vs. 30.8%, χ2 = 6.023, p = 0.014).
CONCLUSION
Compared to clinical signs judgment, OCTLS significantly reduces unnecessary fasciotomy, improves diagnostic accuracy for OCS, and enables non-invasive, dynamic, and quantitative assessment, making it a valuable tool for clinical practice.
Humans
;
Compartment Syndromes/etiology*
;
Male
;
Female
;
Adult
;
Tibial Fractures/surgery*
;
Middle Aged
;
Fasciotomy
;
Edema/etiology*
;
Longitudinal Studies
;
Aged
;
Young Adult
7.Development and evaluation of a competitive ELISA based on a porcine neutralizing Fab antibody against Senecavirus A.
Yubin LIANG ; Xueqing MA ; Yixuan HE ; Caihe WANG ; Kun LI ; Pinghua LI ; Yuanfang FU ; Zengjun LU ; Xiaohua DU ; Xia LIU ; Pu SUN
Chinese Journal of Biotechnology 2025;41(7):2748-2759
Senecavirus A (SVA) is a major viral pathogen causing disease in pigs, and effective monitoring of SVA infection is critical for disease control. In this study, we aimed to develop a reliable ELISA method for rapidly detecting neutralizing antibodies against SVA. We used HEK293F cells to express an SVA-specific porcine Fab antibody and verified the biological activity of the Fab antibody by indirect ELISA, immunofluorescence assay, virus neutralization test, and Western blotting. The Fab antibody was biotinylated and used as a competitive antibody to establish a competitive ELISA (C-ELISA) for detecting neutralizing antibodies against SVA. We then evaluated the C-ELISA in terms of sensitivity, specificity, repeatability, and result agreement rate with the VNT. The results showed that we successfully prepared an SVA-specific porcine Fab antibody, which showed high affinity for SVA. We named this antibody 1M33Fab and designated it as Bio-1M33Fab after biotin labeling. The assay conditions were optimized as follows: the coating concentration of SVA particles being 1 μg/mL, the working concentration of Bio-1M33Fab being 0.5 μg/mL, the optimal serum dilution of 1:10, and the optimal dilution of enzyme-labeled avidin being 1:30 000. At a percent inhibition (PI) of 47%, the assay demonstrated the highest sensitivity (96.88%) and specificity (100%), with no cross-reactivity observed with the positive sera of major porcine viral diseases. The intra-assay coefficient of variation ranged from 1.12% to 7.34%, while the inter-assay coefficient of variation ranged from 1.10% to 8.97%, indicating good repeatability. In the detection of 224 clinical pig serum samples, C-ELISA and VNT showed a result agreement rate of 93.75%. In conclusion, we successfully develop a C-ELISA method for detecting neutralizing antibodies against SVA by using a porcine-derived Fab antibody, which lays a foundation for the development of detection kits.
Animals
;
Swine
;
Antibodies, Neutralizing/immunology*
;
Enzyme-Linked Immunosorbent Assay/methods*
;
Immunoglobulin Fab Fragments/immunology*
;
Antibodies, Viral/immunology*
;
Picornaviridae/immunology*
;
Humans
;
HEK293 Cells
;
Swine Diseases/diagnosis*
;
Picornaviridae Infections/diagnosis*
8.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Perimenopausal Syndrome
Shiwan HU ; Haiyan LIANG ; Kun MA ; Xiaona MA ; Zihan FANG ; Wenpei BAI ; Xinmin LIU ; Hongtian LI ; Fengmei LIAN ; Wei ZHANG ; Lihua QIN ; Min SHANG ; Ailuan LAI ; Xiuxiang TENG ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):234-242
Perimenopausal syndrome (MPS), a common endocrine system disease, is one of the diseases responding specifically to traditional Chinese medicine (TCM). The China Association of Chinese Medicine organized experts in endocrinology, gynecology, and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine, TCM, and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency, with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause, whereas such a therapy has certain risks, necessitating close monitoring of adverse reactions. Moreover, the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes, sweating, sleep disorders, and emotional abnormalities of MPS without causing obvious adverse reactions. However, its efficacy is slower than the hormone replacement therapy, and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First, an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second, high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third, efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.
9.Mechanism and research progress of S100A8/A9 in the microenvironment before high-risk tumor metastasis
Hai-Xia MING ; Zhao-Hua LIU ; Yan-Jun WANG ; Ming SHEN ; Yan-Wen CHEN ; Yang LI ; Ling-Ling YANG ; Qian-Kun LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1991-1995
S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.
10.Effects of total flavonoids of Oxytropis falcata Bunge on CCl4-induced liver fibrosis in rats
Tian-Yan YANG ; Xin-Huan MA ; Zhi-Wei XU ; Rong-Kun LI ; Fang-Xiong MA ; Bao-Feng HE ; Liang CHEN ; Xiao-Qing CHEN ; Jun ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(14):2073-2077
Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9%NaCl),model group(intraperitoneal injection of 40%CC14 peanut oil solution induced HF model,intragastric administration of 0.9%NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

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