[Epidemiological characteristics of human respiratory syncytial virus in Hubei Province from 2016 to 2023].

Objective: To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023. Methods: ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed. Results: From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) (P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion: SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.

HSA-MIR-183-3P TARGETING ATAXIA-TELANGIECTASIA MUTATED PROTEIN REGULATION OF NF-ΚB SIGNALING PATHWAY AFFECTS CELLULAR SENESCENCE CAUSED BY DNA DAMAGE IN LUMBAR DISC DEGENERATION.

Aims: To test the effect of Hsa-miR-183-3p on cell aging and disc degeneration in lumbar intervertebral disc. Methods: This study combined clinical research with basic cell experiment, analyzing clinical data from patients with lumbar disc degeneration and traumatic lumbar spine fracture, as well as the differences in baseline data. The degree of lumbar disc injury in patients of different ages was also compared. Differentially expressed miRNAs were predicted via GEO database, and qPCR confirmation was determined by collecting cartilage endplates from two groups. ACAN, Col2A1, p16, p21, and p53 were detected by immunofluorescence, Western blot and qPCR in human nucleus pulposus cells. Changes of cell senescence were detected. The binding of Hsa-miR-183-3p to ataxia-telangiectasia mutated protein was confirmed by dual luciferase reporter assay. Results: Degenerative discs showed elevated expression of hsa-miR-183-3p, which may be upregulated by TNF-α via NF-κB signaling pathway and target ataxia-telangiectasia mutated protein regulation. Conclusion: Degeneration of the intervertebral disc can be accelerated by TNF-α. Additionally, Hsa-miR-183-3p passed NF-κB signaling pathway is blocked via up-regulation of TNF-α to reduce inflammation via targeting ataxia-telangiectasia mutated protein. As a result, this negative feedback mechanism may assist in maintaining a low degenerative load and preserving chronic disc degeneration.

[Efficacy analysis of Venetoclax combined with TKI and dexamethasone-containing low-dose chemotherapy for relapsed/refractory Ph+acute B-lymphoblastic leukemia].

The clinical data of five cases of relapsed/refractory (R/R) Philadelphia chromosome-positive acute B-lymphocytic leukaemia (Ph+B-ALL) treated with Bcl-2 inhibitor venetoclax combined with tyrosine kinase inhibitor (TKI) and dexamethasone-containing low-dose chemotherapy regimen at Zhengzhou University Cancer Hospital were analyzed, and the efficacy and safety were evaluated. Ponatinib was used in two of the five patients with T315I mutation, and flumatinib was used in other three patients. The results showed that, of the four minimal residual disease (MRD) positive patients, three achieved complete molecular remission (CMR) in the short term and one was ineffective. Another patient with morphological recurrence reached CR in one month. The overall response rate was 80%. Treatment related adverse reactions included mild skin pigmentation, gastrointestinal reactions, fatigue, and grade Ⅰ-Ⅱ bone marrow suppression.

Double Superconducting Dome and Triple Enhancement of T_{c} in the Kagome Superconductor CsV_{3}Sb_{5} under High Pressure.

CsV_{3}Sb_{5} is a newly discovered Z_{2} topological kagome metal showing the coexistence of a charge-density-wave (CDW)-like order at T^{*}=94 K and superconductivity (SC) at T_{c}=2.5 K at ambient pressure. Here, we study the interplay between CDW and SC in CsV_{3}Sb_{5} via measurements of resistivity, dc and ac magnetic susceptibility under various pressures up to 6.6 GPa. We find that the CDW transition decreases with pressure and experience a subtle modification at P_{c1}≈0.6-0.9 GPa before it vanishes completely at P_{c2}≈2 GPa. Correspondingly, T_{c}(P) displays an unusual M-shaped double dome with two maxima around P_{c1} and P_{c2}, respectively, leading to a tripled enhancement of T_{c} to about 8 K at 2 GPa. The obtained temperature-pressure phase diagram resembles those of unconventional superconductors, illustrating an intimated competition between CDW-like order and SC. The competition is found to be particularly strong for the intermediate pressure range P_{c1}≤P≤P_{c2} as evidenced by the broad superconducting transition and reduced superconducting volume fraction. The modification of CDW order around P_{c1} has been discussed based on the band structure calculations. This work not only demonstrates the potential to raise T_{c} of the V-based kagome superconductors, but also offers more insights into the rich physics related to the electron correlations in this novel family of topological kagome metals.

A diagnostic test that uses isothermal amplification and lateral flow detection sdaA can detect tuberculosis in 60 min.

AIMS: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is now the leading cause of death from infectious disease, thus rapid diagnostic and screening techniques for TB are urgently needed. METHODS AND RESULTS: Here, a detection of MTB using multiple cross displacement amplification coupling with nanoparticles-based lateral flow device (MCDA-LFD) was developed and validated, targeting the specific sdaA gene. The whole detection procedure, including rapid genomic DNA extraction (15 min), amplification (30 min) and result reporting (2 min), was completed within 50 min. No cross-reaction with non-mycobacteria and non-tuberculous mycobacteria (NTM) strains was observed. The sensitivity of sdaA-MCDA-LFD, Xpert MTB/RIF assay and culture results was 81·6, 48·3 and 37·9%, respectively, in TB patients. Among positive culture samples, the sensitivity of sdaA-MCDA-LFD and Xpert MTB/RIF assay was 93·9% (31/33) and 81·8% (27/33), respectively. Among culture-negative samples, the sensitivity of sdaA-MCDA-LFD and Xpert MTB/RIF assay was 74·1% (40/54) and 27·8% (15/54), respectively. The specificity of sdaA-MCDA-LFD and Xpert MTB/RIF was 95·4% (62/65) and 100% (65/65) in clinical samples from non-TB patients. CONCLUSION: The sdaA-MCDA-LFD assay was a rapid, simple, specific and sensitive TB diagnostic test. SIGNIFICANCE AND IMPACT OF THE STUDY: The sdaA-MCDA-LFD assay holds promise for application as a useful point-of-care test to detect MTB, and will play an important role in controlling and preventing TB.

Transfusion support during childbirth for a woman with anti-U and the RHD*weak D type 4.0 allele.

D- red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U-, D- RBC units. We obtained 3 U- RBC units, including 1 D- unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D- restriction for the limited U- RBC supply. The procured U-, D- RBC unit was frozen with 14 days of shelf-life remaining. To conserve D- RBC units, not limited to U-, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:1-4 .D­ red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U­, D­ RBC units. We obtained 3 U­ RBC units, including 1 D­ unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D­ restriction for the limited U­ RBC supply. The procured U­, D­ RBC unit was frozen with 14 days of shelf-life remaining. To conserve D­ RBC units, not limited to U­, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:1­4 .

[Study of PA-HSOS severity grading to predict the prognosis of patients with PA-HSOS treated by transjugular intrahepatic portosystemic shunt].

Objective: To explore pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) severity grading to predict the prognostic value for PA-HSOS patients treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: Clinical data of patients with PA-HSOS who were critically ill or had ineffective drug treatment and underwent TIPS treatment from December 2013 to September 2019 were retrospectively analyzed. PA-HSOS severity grading criteria in adult was quoted, revised and defined from the European Group for Blood and Marrow Transplantation (EBMT). The survival time, the rate of shunt dysfunction and the incidence of postoperative hepatic encephalopathy in different severity groups after TIPS were compared. Univariate Cox or Binomial Logistic regression analysis was used to evaluate the impact of each variable. Variables with P < 0.1 were regarded as statistically significant variables for the prognosis, and were introduced into Cox or Binomial Logistic regression hierarchical regression analysis as controlled covariates. PA-HSOS severity grading was analyzed as dummy variables. Results: A total of 102 patient data were collected, and the median follow-up time was 14.52 months. The difference in survival time of patients with different severity levels was statistically significant (P = 0.023). The mortality risk in moderate patients was 1.575 times higher than that of mild patients (95%CI: 0.216-11.457, P = 0.654). The mortality risk of severe and very severe patients was 7.424 times higher than that of mild patients (95% CI: 1.612-34.197, P = 0.010). There was no statistically significant difference in postoperative hepatic encephalopathy recurrence rate and shunt dysfunction rate (P > 0.05). Conclusion: PA-HSOS severity grading has prognostic value for PA-HSOS patients receiving TIPS treatment, and can be used as an important reference for guiding the timing of TIPS intervention.

Identification of human temporomandibular joint fibrocartilage stem cells with distinct chondrogenic capacity.

OBJECTIVE: This study was aimed to identify the residence of human fibrocartilage stem cells (hFCSCs), characterize their stem cell properties and investigate the functional mechanisms which regulate fibrocartilage stem cells (FCSCs) toward chondrogenic differentiation during cartilage homeostasis and repairing. METHODS: Cytological characteristics of hFCSCs and human orofacial mesenchymal stem cells (hOFMSCs) were analyzed. Chondrogenic potential of hFCSCs was compared with hOFMSCs both in vitro and in vivo. Regulatory role of SOX9 during FCSCs chondrogenesis was studied by shRNA interference in vitro, and by GFP+ FCSCs treatment in rat condylar cartilage defect model. SOX9 expression was also examined in temporomandibular joint osteoarthritis (TMJOA) patients' cartilage surface. RESULTS: hFCSCs exhibited typical mesenchymal stem cell characteristics, with significantly stronger chondrogenic capability compared to hOFMSCs. Moreover, hFCSCs showed remarkably increased expression of SOX9. During cartilage pellet culture, there was stronger SOX9 expression in hFCSCs than hOFMSCs. SOX9 shRNA interference downregulated chondrogenic capability of hFCSCs in vitro, as well as disrupting migration and chondrogenic differentiation of GFP+ FCSCs toward mature chondrocytes in rat condylar cartilage defect. Of note, SOX9 expression was also found suppressed in the condylar superficial zone of TMJOA patients. CONCLUSION: We found the existence of FCSCs in human TMJ cartilage, and characterized their distinct stem cell features. SOX9 is essential for hFCSCs chondrogenic differentiation, and a comprehensive understanding of the regulatory role of SOX9 in hFCSCs would be important for exploring potential intervention strategy of condylar cartilage degradation during TMJ disorders.

[The safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with inermediate or higer-risk myelodysplastic syndrome].

To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with intermediate or high-risk myelodysplastic syndrome (MDS). Three of the total 11 MDS patients achieved complete remission (CR) and 6 achieved hematological improvement (HI), 1 stable disease (SD), and 1 progressive disease (PD). One patient was treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median follow-up time was 413(90-1 275) d. Nine patients were still alive. Low dose subcutaneous decitabine combined with arsenic trioxide can be an alternative regimen for intermediate or high-risk MDS patients.

[Long-term clinical outcome of children and adolescents with Burkitt's lymphoma treated with rituximab combined with modified NHL-BFM-90 regimen].

Objective: To evaluate the efficacy and safety of rituximab combined with the modified NHL-BFM-90 protocol in childhood and adolescence with Burkitt's lymphoma (BL). Methods: A retrospective analysis of 67 untreated childhood and adolescence patients with BL was made. All patients were treated with the modified NHL-BFM-90 protocol with or without rituximab. Results: The 64 patients (95.52%) achieved complete remission (CR), 3 patients (4.48%) partial remission (PR), and the overall response rate (CR+PR) was 100%. 67 patients were followed up for a median of 44 (3-89) months. The 3 and 5-year overall survival (OS) were 92.54% and 88.98%, respectively. The 3 and 5-year progression-free survival (PFS) were all 90.34%. The 5-year OS were 100%,91.7% and 80.0% in low risk, moderate risk and high risk group, respectively, and the difference was statistically significant (P=0.048). Of the 67 patients, 55 patients (82.09%) were treated with rituximab plus chemotherapy. Compared with the 5-year OS and PFS of 74.3% and 78.6% in the chemotherapy group, the 5-year OS and PFS in the rituximab plus chemotherapy group were 95.2% and 95.5%, respectively, and the difference was statistically significant (P value was 0.021, and 0.036, respectively). Major toxicity was myelosuppression and mucositis. No treatment related death was found. Conclusions: Rituximab combined with the modified NHL-BFM-90 protocol was highly effective for children and adolescents with BL, and significantly improved long-term survival.

[Efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio in patients with diffuse large B-cell lymphoma].

Objective: To investigate the efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio (LMR) in patients with diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of 261 patients with DLBCL in the Affiliated Cancer Hospital of Zhengzhou University between March 2012 to March 2018, were analyzed retrospectively. The optimal cut-off values of LMR was determined using the receiver operating characteristic curve (ROC) method. Patients were divided into low LMR group and high LMR group according to the optimal cut-off value. The changes of LMR before and after treatment in two groups were dynamically monitored, and the relationship between LMR and efficacy and survival were analyzed. Results: Complete remission (CR) rate in patients with high LMR (64.7%) before treatment was significantly higher than that in patients with low LMR (33.3%) (P<0.05). Compared with the 5-year overall survival(OS) and progress free survival(PFS) (56.96% and 43.55%, respectively) in the low LMR group, the 5-year OS and PFS (82.92% and 66.25%, respectively) in the high LMR group were higher, and the difference was statistically significant (all P<0.05). Patients with elevated LMR after treatment in the high or low LMR group had a significant higher 5-year OS and PFS compared with patients with LMR reduction(P<0.05). LMR in both high and low LMR group were significantly lower at the last follow-up than those at the disease recurrence (all P<0.05). Both single and multivariate analyses showed that low LMR was an independent prognostic factor in patients with DLBCL (all P<0.05). Conclusions: LMR can be used as an indicator of risk stratification, efficacy, disease replase and prognosis in patients with DLBCL. Low LMR before and after treatment were poor prognostic factors in patients with DLBCL.

Integrative radiomics expression predicts molecular subtypes of primary clear cell renal cell carcinoma.

AIM: To identify combined positron-emission tomography (PET)/magnetic resonance imaging (MRI)-based radiomics as a surrogate biomarker of intratumour disease risk for molecular subtype ccA and ccB in patients with primary clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: PET/MRI data were analysed retrospectively from eight patients. One hundred and sixty-eight radiomics features for each tumour sampling based on the regionally sampled tumours with 23 specimens were extracted. Sparse partial least squares discriminant analysis (SPLS-DA) was applied to feature screening on high-throughput radiomics features and project the selected features to low-dimensional intrinsic latent components as radiomics signatures. In addition, multilevel omics datasets were leveraged to explore the complementing information and elevate the discriminative ability. RESULTS: The correct classification rate (CCR) for molecular subtype classification by SPLS-DA using only radiomics features was 86.96% with permutation test p=7×10-4. When multi-omics datasets including mRNA, microvascular density, and clinical parameters from each specimen were combined with radiomics features to refine the model of SPLS-DA, the best CCR was 95.65% with permutation test, p<10-4; however, even in the case of generating the classification based on transcription features, which is the reference standard, there is roughly 10% classification ambiguity. Thus, this classification level (86.96-95.65%) of the proposed method represents the discriminating level that is consistent with reality. CONCLUSION: Featured with high accuracy, an integrated multi-omics model of PET/MRI-based radiomics could be the first non-invasive investigation for disease risk stratification and guidance of treatment in patients with primary ccRCC.

Transcriptome and proteome analyses reveal complex mechanisms of reproductive diapause in the two-spotted spider mite, Tetranychus urticae.

Although a variety of factors underlying diapause have been identified in arthropods and other organisms, the molecular mechanisms regulating diapause are still largely unknown. Here, to better understand this process, we examined diapause-associated genes in the two-spotted spider mite, Tetranychus urticae, by comparing the transcriptomes and proteomes of early diapausing and reproductive adult females. Amongst genes underlying diapause revealed by the transcriptomic and proteomic data sets, we described the noticeable change in Ca2+ -associated genes, including 65 Ca2+ -binding protein genes and 23 Ca2+ transporter genes, indicating that Ca2+ signalling has a substantial role in diapause regulation. Other interesting changes in diapause included up-regulation of (1) glutamate receptors that may be involved in synaptic plasticity changes, (2) genes involved in cytoskeletal reorganization including genes encoding each of the components of thick and thin filaments, tubulin and members of integrin signalling and (3) genes involved in anaerobic energy metabolism, which reflects a shift to anaerobic energy metabolism in early diapausing mites.

[The clinical safety and efficacy of low dose subcutaneous decitabine in treating acute myeloid leukemia and intermediate- or higer-risk myelodysplastic syndromes in the elderly patients].

To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine regimen in patients with acute myeloid leukemia (AML) and intermediate- or higer-risk myelodysplastic syndrome (MDS). Of 6 AML cases, 2 achieved complete remission (CR), 2 with partial remission(PR), 1 with stable disease(SD), 1 with progressive disease(PD). As to the 8 MDS patients, one achieved CR and 6 with hematologic improvement (HI), 1 case SD. Low dose subcutaneous decitabine regimen could be an alternative choice of older AML or MDS patients.

[Clinical characteristics and analysis of patients with hematological diseases and HCV-Ab positive].

Objective: To observe the biological characteristics of patients with hematological diseases and hepatitis C antibodies positive and to investigate features of HCV infection and reactivation. Methods: A total of 85 patients with seropositive HCV at the hematology ward in Henan Cancer Hospital between October 2010 and October 2015 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed. Original disease treatment information was obtained from the medical records. Results: The positive rate of HCV-Ab was 1.2%, which was significantly higher than that of the general population(1.2% vs 0.4%, P<0.001). Of the 25 patients who showed anti-HCV seroconversion during the period of treatment or follow-up, serum ALT level was elevated in 15 patients(60.0%)and AST level got synchronous increase in 14 patients (56.0%). Of the 85 patients with positive HCV-Ab, 13 (15.3%) patients suffered from HCV reactivation with hepatic injury in varying degrees after chemotherapy or HSCT. Conclusions: Patients with hematological diseases have high incidence of HCV infection and reactivation, and most of them have hepatic injury. Chemotherapy and HSCT are important risk factors for HCV reactivation.

Effects of repetitive transcranial magnetic stimulation on motor recovery and motor cortex excitability in patients with stroke: a randomized controlled trial.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) changes the excitability of the motor cortex and thereby has the potential to enhance motor recovery after stroke. This randomized, sham-controlled, double-blind study was to compare the effects of high-frequency versus low-frequency rTMS on motor recovery during the early phase of stroke and to identify the neurophysiological correlates of motor improvements. METHODS: A total of 69 first-ever ischemic stroke patients with motor deficits were randomly allocated to receive five daily sessions of 3-Hz ipsilesional rTMS, 1-Hz contralesional rTMS or sham rTMS in addition to standard physical therapy. Outcome measures included motor deficits, neurological scores and cortical excitability, which were assessed at baseline, after the intervention and at 3-month follow-up. RESULTS: The rTMS groups manifested greater motor improvements than the control group, which were sustained for at least 3 months after the end of the treatment sessions. 1-Hz rTMS over the unaffected hemisphere produced more profound effects than 3-Hz rTMS in facilitating upper limb motor performance. There was a significant correlation between motor function improvement and motor cortex excitability change in the affected hemisphere. CONCLUSIONS: Repetitive transcranial magnetic stimulation is a beneficial neurorehabilitative strategy for enhancing motor recovery in the acute and subacute phase after stroke.

[Thalidomide combined with interferon and interleukin-2 in treatment of relapsed or refractory acute myelogenous leukemia].

In 12 patients with relapsed or refractory acute myelogenous leukemia (AML), the efficacy and safety of a novel regimen, namely thalidomide combined with interferon and interleukin 2 (IL-2), were initially explored.All the patients have received the triple-drug regimen for at least one cycle.Three patients achieved incomplete remission (CRi), 3 patients with partial remission.The overall response rate (ORR) was 50%.

[Expression changes of aldehyde dehydrogenase 1A1 in rat cryptorchidism and normal testis].

Objective: To study the mRNA and protein expression of aldehyde dehydrogenase 1A1(ALDH1A1)in rat cryptorchidism and normal testis. Methods: We established the cryptorchidism model by flutamide and took normal testis as normal group.The testicular tissue samples were collected on 15 days, 45 days, and 90 days after birth respectively.The expression of ALDH1A1 in rat cryptorchidism and normal testis were investigated by real-time PCR, Western blot and immunohistochemisty intissue microarray. Results: The mRNA expression of ALDH1A1 in cryptorchidism group in infant, adolescent and adult period were 1.01±0.19, 1.60±0.32, 0.75±0.16, and 1.66±0.23, 0.52±0.08, 0.15±0.10 in normal group, respectively.The expression of ALDH1A1 in cryptorchidism group was significantly lower than that in normal group in infant period, but it was significantly higher than that in the normal group in adolescent and adult period(P<0.05). Conclusions: The expression of ALDH1A1 was different in different age period during the process of testicular development of rat. It showed an important relationship between ALDH1A1 and cryptorchidism.

Human kallikrein 5 as a novel prognostic biomarker for triple-negative breast cancer: tissue expression analysis and relationship with disease course.

The purposes of this study were to analyze the expression and distribution of human kallikrein 5 (hK5) in triple-negative breast cancer (TNBC) tissues, to establish a standard operating procedure (SOP) for its immunohistochemical assay, and to evaluate the possibility of hK5 being a prognostic biomarker for TNBC. Recombinant hK5 protein and specific antibody were prepared, and the expression and distribution of hK5 in TNBC tissues were detected using immunohistochemistry. An SOP for immunohistochemical staining of hK5 in TNBC tissues was established to allow automatic staining under optimized conditions. The resulting images were digitized for evaluation and statistical analysis via a human scoring system. Our results showed that expression of hK5 protein could predict the progression of TNBC. Pearson's chi-square test results showed that high hK5 expression in tumor stromal cells was significantly correlated with distal metastasis (P = 0.039). A high staining score for lymphocyte infiltration in tumor stroma was significantly correlated with low histological grade of tumor (P = 0.025). Univariate and multivariate Cox regression analyses verified that the staining score for hK5 in tumor stromal cells may be a biomarker for poor prognosis in TNBC patients (univariate HR = 2.289, 95%CI = 1.362-3.848, P = 0.002; multivariate HR = 2.105, 95%CI = 1.189-3.727, P = 0.011). In conclusion, the expression level of hK5 in tumor stromal cells is a promising biomarker for poor prognosis in TNBC. Patients with high histological grade are more prone to distal metastasis and aggressive tumor progression.