1.Analysis of the changes in intestinal microbiota of patients with moderate to severe acne based on 16S rRNA high-throughput sequencing technology
Shichao JIANG ; Xiaomeng WANG ; Zheng CHEN ; Song QIAO ; Fan YANG ; Birong GUO
Acta Universitatis Medicinalis Anhui 2026;61(1):98-103
ObjectiveTo explore the relationship between acne vulgaris and gut microbiota. MethodsA total of 29 clinical cases diagnosed with moderate-to-severe acne vulgaris and 26 healthy individuals as control subjects were recruited. Fecal specimens were collected from all participants, and further analysis of gut microbial communities was performed by leveraging high-throughput sequencing techniques that target the hypervariable regions of 16S rRNA genes. ResultsAssociations between acne vulgaris and alterations in gut microbiota were identified. At the phylum level, the relative abundance of Bacteroidota exhibited a statistically significant elevation in the acne vulgaris cohort when compared with the healthy control group (P<0.01), while Cyanobacteria was significantly lower in the acne group (P<0.01). At the genus level, the top five different bacterial taxa in both groups were Bacteroides, Escherichia⁃Shigella, Klebsiella, Roseburia, and Parabacteroides. Among them, Bacteroides, Roseburia, and Parabacteroides were more abundant in acne patients. Linear discriminant analysis identified five biomarkers all belonging to the Bacteroidota phylum in the acne and control groups. These biomarkers belong to the phylum Bacteroidetes. ConclusionThere are significant differences in the composition of intestinal microbiota between acne patients and healthy people. Changes in the richness of specific bacterial genera may become new targets for the diagnosis and treatment of acne.
2.Fangxia Dihuang Formula regulates PERK/eIF2α axis-mediated microglial polarization in treatment of breast cancer complicated by depression.
Hong-Qiao FAN ; Ying-Yi FAN ; Xiao-Hua PEI
China Journal of Chinese Materia Medica 2025;50(14):4015-4025
Study on the mechanism of Fangxia Dihuang Formula(FXDH) in treating breast cancer complicated with depression through the regulation of M1/M2 microglial polarization via the PERK/eIF2α axis. In addition to control group and 4T1 group, a mouse model of breast cancer complicated with depression was established using 4T1 cells combined with corticosterone. The mice were divided into model group, PERK/eIF2α signaling axis agonist(CCT020312, 2 mg·kg~(-1)·d~(-1)) group, CCT020312(2 mg·kg~(-1)·d~(-1)) + FXDH(13.65 g·kg~(-1)·d~(-1)) group, FXDH(13.65 g·kg~(-1)·d~(-1)) group, FXDH(13.65 g·kg~(-1)·d~(-1)) + Capecitabine Tablets(CAP, 390 mg·kg~(-1)·d~(-1)) group, and Fluoxetine Hydrochloride Capsules(FXT, 2.6 mg·kg~(-1)·d~(-1)) + CAP(390 mg·kg~(-1)·d~(-1)) group, with continuous intervention for 21 d. Depression-like behaviors in mice were assessed through sugar preference test and open field test. Hematoxylin-eosin(HE) staining was used to evaluate the morphology of tumor and hippocampal DG region neurons. Nissl staining was employed to detect changes in Nissl bodies in the hippocampal CA3 region. Immunofluorescence was used to observe cluster of differentiation 86(CD86)/ionized calcium-binding adapter molecule 1(Iba-1) and cluster of differentiation 206(CD206)/Iba-1 in hippocampal tissue. Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression of M1-type microglia [interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)] and M2-type [arginase-1(Arg-1), IL-10] in hippocampal tissue. Western blot was used to detect the protein expression of key factors in the PERK/eIF2α axis, including PERK, eIF2α, activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) in hippocampal tissue. The results showed that compared to model group/CCT020312 + FXDH group, FXDH group increased sugar preference index, total movement distance, central zone distance, and central zone entries; reduced tumor mass and volume; tumor cells were sparsely arranged, with a smaller nuclear-to-cytoplasmic ratio and reduced nuclear division figures, increased Nissl body count, and alleviated neuronal nuclear pyknosis; increased CD206-positive M2-type microglia expression, decreased CD86/Iba-1-positive M1-type microglia expression; reduced IL-6 and TNF-α mRNA expression, and increased Arg-1 and IL-10 mRNA expression; downregulated PERK, eIF2α, ATF4, and CHOP protein expression levels. The results indicate that the mechanism of FXDH in treating breast cancer complicated with depression may be related to inhibiting the activity of the PERK/eIF2α axis, reducing the proportion of M1-type microglia, increasing the proportion of M2-type microglia, thereby suppressing neuronal immune inflammation, improving depressive symptoms, and subsequently delaying the progression of breast cancer.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Female
;
Microglia/cytology*
;
Mice
;
Depression/complications*
;
eIF-2 Kinase/genetics*
;
Humans
;
Breast Neoplasms/psychology*
;
Eukaryotic Initiation Factor-2/genetics*
;
Mice, Inbred BALB C
;
Signal Transduction/drug effects*
;
Cell Line, Tumor
3.Comparative epidemiology and treatment outcomes at trauma centers: A cross-national analysis of the United States and China.
Yong FU ; Liu-Yi FAN ; Xin-Jie LUO ; Lei LI ; Delbrynth P MITCHAO ; Kenji INABA ; Guan-Qiao LIU ; Bin YU
Chinese Journal of Traumatology 2025;28(6):399-403
PURPOSE:
Although there are significant differences between China and the United States (US) in trauma medical services, there has been no direct comparative research on the epidemiological data of trauma centers between the 2 countries. This study aims to fill this research gap by directly comparing trauma centers in China and the US, providing valuable data and insights for the development of trauma centers in both countries, promoting academic exchange and cooperation internationally, and enhancing the level of global trauma medical care.
METHODS:
This is a multicenter retrospective descriptive study. Data were collected for trauma patients with an injury severity score ≥16 treated from September 2013 to September 2019 at 2 hospital trauma centers in these 2 countries. Detailed clinical data (including injury mechanism, age, injury site, injury severity score, pre-hospital transport time, whether blood transfusion was performed, whether resuscitative thoracotomy was conducted, hospital and intensive care unit stay duration, the number of organ donor patients, mortality rates, and costs) were meticulously compiled and retrospectively analyzed to identify differences between the 2 trauma centers. The comparison was conducted using SPSS 23 software. Continuous variables are reported as median (Q1, Q3), and Mann Whitney U test is used to compare the median of continuous variables. Use clinically relevant critical points to classify continuous variables, with categorical variables represented as n (%), and comparisons were made between the 2 groups using the χ2 test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05.
RESULTS:
These results point to significant differences in trauma center capacity, pre-hospital transport times, treatment procedures, hospital stay duration, mortality rates, and costs between the 2 centers. The volume of patients in trauma centers is less in China (2465 vs. 5288). Pre-hospital transport time was notably longer in China (180 min vs. 14 min), and the rate of emergency blood transfusions was lower in China (18.4% vs. 50.6%), Emergency thoracotomy was not performed in China but was conducted in 9.8% of cases in the US. Hospitalization costs were significantly lower in China than in the US ($5847 vs. $75,671).
CONCLUSION
There are clear differences in trauma center capacity (number of patients treated), pre-hospital transport time, age distribution of injured patients, injury mechanisms, injury sites, whether emergency thoracotomy is performed, hospital costs, and length of stay between the 2 trauma centers in China and America. Understanding these differences can help us further recognize the characteristics of Eastern and Western trauma patients.
Humans
;
China/epidemiology*
;
Trauma Centers/statistics & numerical data*
;
Retrospective Studies
;
United States/epidemiology*
;
Male
;
Female
;
Wounds and Injuries/therapy*
;
Middle Aged
;
Adult
;
Injury Severity Score
;
Length of Stay/statistics & numerical data*
;
Treatment Outcome
4.Clinical Characteristics and Prognosis of Patients with IgD Multiple Myeloma.
Yong-Qian ZHANG ; Ji-Sheng ZHAO ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Qiao-Lin CHEN ; Qi-Ke ZHANG
Journal of Experimental Hematology 2025;33(2):437-441
OBJECTIVE:
To investigate the clinical characteristics and prognosis of patients with IgD multiple myeloma (MM).
METHODS:
The clinical data of 8 patients with IgD MM admitted to Gansu Provincial Hospital from September 2013 to February 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized.
RESULTS:
Among the 8 enrolled patients, there were 4 males and 4 females, with a median age of 60 (44-74) years. All patients had symptoms of renal insufficiency and anemia. There were 3 cases of bone invasion, 3 cases of splenomegaly, 7 cases of IgD-λ type, and 1 case of IgD-κ type. FISH examination was performed in 7 cases, and 6 of them were positive for 1q21 . There were 6 cases in DS stage III and 2 cases in DS stage II; According to ISS staging, there were 6 cases in stage III, 1 case in stage II, and 1 case in stage I; According to R-ISS staging, there were 5 cases in stage III and 3 cases in stage II. All patients received bortezomib-based combination chemotherapy, with 1 case undergoing autologous stem cell transplantation (ASCT) and 2 cases receiving daratumumab in combination. The median treatment period was 6 (1-15) cycles. The short-term efficacy was evaluated after 4-6 courses of treatment. Among the 6 patients with assessable efficacy, 1 case experienced disease progression (PD), and 5 cases achieved complete remission (CR). The median follow-up time was 26 (11-33) months, and the median progression-free survival (PFS) and median overall survival (OS) of the patients were 11.25 (3-26) months and 18.5 (4-33) months, respectively. Among the 8 patients, 4 cases died. Among the deceased patients, 3 cases were in R-ISS stage III and 3 cases were 1q21 positive. 2 of the 5 patients with early CR died due to disease progression.
CONCLUSION
The incidence of IgD MM is low, the symptoms of early renal damage, blood system damage and bone erosion in IgD MM patients are obvious, and the median survival time is short. ASCT and / or daratumumab may bring lasting relief for IgD MM patients, but large-scale clinical studies are still needed.
Humans
;
Multiple Myeloma/therapy*
;
Middle Aged
;
Male
;
Female
;
Aged
;
Prognosis
;
Immunoglobulin D
;
Adult
;
Retrospective Studies
5.The Significance of Bone Marrow Plasma Cell Percentage and Immature Plasma Cells in the Prognosis of Newly Diagnosed Multiple Myeloma Patients.
Yuan-Yuan ZHANG ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Fei LIU ; Qiao-Lin CHEN ; Yang-Yang ZHAO ; Xiu-Juan HUANG ; Yang CHEN
Journal of Experimental Hematology 2025;33(2):469-474
OBJECTIVE:
To explore the significance of the plasma cell percentage and immature plasma cells in the prognosis of patients with multiple myeloma (MM).
METHODS:
The clinical data of 126 newly diagnosed MM patients in Gansu Provincial Hospital from June 2017 to November 2022 were retrospectively analyzed. The enrolled patients were divided into a higher plasma cell percentage group (group A) and a lower plasma cell percentage group (group B) according to the median plasma cell percentage (33.5%). The clinicopathological data of the two groups were compared, and the effect of plasma cell percentage on the prognosis of MM patients was analyzed using survival curves. On this basis, group A and group B were divided into subgroups with immature plasma cells (A1 group, B1 group) and subgroups without immature plasma cells (A2 group, B2 group), respectively, then the survival curves were used to analyze the effect of immature plasma cells on the prognosis of MM patients.
RESULTS:
Among the 126 patients with MM, the proportions of patients with ISS stage III, elevated β2-microglobulin(β2-MG) level, and immature plasma cells in Group A were significantly higher compared those in Group B ( P =0.015, P =0.028, P =0.010). The median overall survival(OS) and progression-free survival(PFS) of group A were 32 months and 10 months, respectively. The median OS of group B was not reached, and the median PFS was 32 months. The 3-year OS rates of patients in group A and group B were 46.7% and 62.2%, respectively ( P =0.021), and the 3-year PFS were 29.2% and 42.5%, respectively ( P =0.033). There were no significant differences in OS and PFS between group A1 and group A2, or between group B1 and group B2 ( P >0.05). Multivariate COX survival analysis showed that the plasma cell percentage ≥33.5%(HR=1.253, 95%CI : 0.580-2.889, P =0.018), age ≥65 years (HR=2.206, 95%CI : 1.170-3.510, P =0.012), lactate dehydrogenase(LDH) ≥250 U/L (HR=1.180, 95%CI : 0.621-2.398, P =0.048) and β2-MG ≥3.5 mg/L (HR=1.507, 95%CI : 0.823-3.657, P =0.036) were independent risk factors affecting OS in MM patients.
CONCLUSION
MM patients with a higher plasma cell percentage (≥33.5%) at the initial diagnosis have a later disease stage, poorer OS and PFS, compared to the patients with a lower percentage(<33.5%) of plasma cells. The presence or absence of immature plasma cells has no significant impact on the survival of MM patients.
Humans
;
Multiple Myeloma/pathology*
;
Prognosis
;
Plasma Cells/cytology*
;
Retrospective Studies
;
Male
;
Female
;
Middle Aged
;
Aged
;
Bone Marrow
6.Clinical Characteristics and Prognosis of 7 Patients with T-Cell Large Granular Lymphocytic Leukemia.
Yong-Qian ZHANG ; Yuan-Yuan ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Qiao-Lin CHEN ; Qi-Ke ZHANG ; Ji-Sheng ZHAO
Journal of Experimental Hematology 2025;33(3):706-710
OBJECTIVE:
To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL).
METHODS:
The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively.
RESULTS:
Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×109 /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 + CD4- CD8 +), 6 cases were CD57 +, 3 cases were TCRα/β +, and 3 cases were TCRγ/δ +. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving.
CONCLUSION
The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans
;
Leukemia, Large Granular Lymphocytic/diagnosis*
;
Male
;
Middle Aged
;
Female
;
Aged
;
Prognosis
;
Adult
;
Aged, 80 and over
;
Retrospective Studies
7.Exploration and Practice of Performance Evaluation System for Large Medical Equipment Based on Internet of Things Technology.
Chang SU ; Caixian ZHENG ; Linling ZHANG ; Yunming SHEN ; Kai FAN ; Tingting DONG ; Hangyan ZHAO ; Xiaofeng WANG ; Dawei QIAO ; Kun ZHENG
Chinese Journal of Medical Instrumentation 2025;49(2):191-196
Medical equipment, as an important indicator of smart hospital evaluation, plays a vital role in hospital operations. To ensure the safe and efficient operation of medical equipment, a reasonable performance evaluation system is indispensable. This study introduces a platform based on Internet of Things (IoT) technology that connects medical devices and collects data, achieving standardized and structured data processing, and supporting online operational supervision. Through the Delphi method, a performance evaluation system for large medical equipment is constructed, including 4 primary indicators and 22 secondary indicators. DICOM data acquisition devices are used to achieve functions such as efficiency analysis, benefit analysis, usage evaluation, and decision-making support for medical equipment. The study is still in its early stages, and in the future, it is expected to integrate more types of equipment, achieve rational resource allocation, and significantly impact decision-making for the development of public hospitals.
Internet of Things
;
Delphi Technique
8.Different Acupuncture Therapies for Postherpetic Neuralgia: An Overview of Systematic Reviews and Meta-analysis.
Yun-Fan XIA ; Ruo-Han SUN ; Shi-Min LI ; Yi-Yi WANG ; Rong-Rong LI ; Jian-Qiao FANG
Chinese journal of integrative medicine 2025;31(1):55-67
BACKGROUND:
Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia.
OBJECTIVE:
To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN.
METHODS:
Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
RESULTS:
Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I2=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I2=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups.
CONCLUSIONS
Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).
Humans
;
Neuralgia, Postherpetic/therapy*
;
Acupuncture Therapy/methods*
;
Systematic Reviews as Topic
9.Endothelial Cell Integrin α6 Regulates Vascular Remodeling Through the PI3K/Akt-eNOS-VEGFA Axis After Stroke.
Bing-Qiao WANG ; Yang-Ying DUAN ; Mao CHEN ; Yu-Fan MA ; Ru CHEN ; Cheng HUANG ; Fei GAO ; Rui XU ; Chun-Mei DUAN
Neuroscience Bulletin 2025;41(9):1522-1536
The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals
;
Nitric Oxide Synthase Type III/metabolism*
;
Mice
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Integrin alpha6/genetics*
;
Endothelial Cells/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Stroke/pathology*
;
Vascular Remodeling/physiology*
;
Vascular Endothelial Growth Factor A/metabolism*
;
Mice, Knockout
;
Signal Transduction/physiology*
;
Mice, Inbred C57BL
;
Male
;
Neovascularization, Physiologic/physiology*
10.Comparison of the efficacy, safety, and cost-effectiveness of trastuzumab biosimilar HLX02 and the originator combined with pertuzumab and chemotherapy in the neoadjuvant treatment of patients with HER-2-positive breast cancer
Zixuan LEI ; Die SANG ; Bo LAN ; Ying FAN ; Ruigang CAI ; Yang LUO ; Qiao LI ; Jiayu WANG ; Longmei ZHAO ; Peng YUAN
Chinese Journal of Oncology 2025;47(6):517-524
Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P<0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P>0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P<0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P<0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.

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