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Artificial intelligence (AI) can acquire characteristics that are not yet known to humans through extensive learning, enabling to handle large amounts of pathology image data. Divided into machine learning and deep learning, AI has the advantage of handling large amounts of data and processing image analysis, consequently it also has a great potential in accurately assessing tumour microenvironment (TME) models. With the complex composition of the TME, in-depth study of TME contributes to new ideas for treatment, assessment of patient response to postoperative therapy and prognostic prediction. This leads to a review of the development of AI's application in TME assessment in this study, provides an overview of AI techniques applied to medicine, delves into the application of AI in analysing the quantitative and spatial location characteristics of various cells (tumour cells, immune and non-immune cells) in the TME, reveals the predictive prognostic value of TME and provides new ideas for tumour therapy, highlights the great potential for clinical applications. In addition, a discussion of its limitations and encouraging future directions for its practical clinical application is presented.

Background The tumour–stroma ratio (TSR) is identified as a promising prognostic parameter for breast cancer, but the cutoff TSR value is mostly assessed by visual assessment, which lacks objective measurement. The aims of this study were to optimize the cutoff TSR value, and evaluate its prognosis value in patients with breast cancer both as continuous and categorical variables. Methods Major clinicopathological and follow-up data were collected for a series of patients with breast cancer. Tissue microarray images stained with cytokeratin immunohistochemistry were evaluated by automated quantitative image analysis algorithms to assess TSR. The potential cutoff point for TSR was optimized using maximally selected rank statistics. The association between TSR and 5-year disease-free survival (5-DFS) was assessed by Cox regression analysis. Kaplan–Meier analysis and log-rank test were used to assess the significance in survival analysis. Results The optimal cut-off TSR value was 33.5%. Using this cut-off point, categorical variable analysis found that low TSR (i.e., high stroma, TSR ≤ 33.5%) predicts poor outcomes for 5-DFS (hazard ratio [HR] = 2.82, 95% confidence interval [CI] = 1.81–4.40, P  = 0.000). When TSR was considered as a continuous parameter, results showed that increased stroma content was associated with worse 5-DFS (HR = 1.71, 95% CI = 1.34–2.18, P  = 0.000). Similar results were also obtained in three molecular subtypes in continuous and categorical variable analyses. Moreover, in the Kaplan–Meier analysis, log-rank test showed that low TSR displayed a worse 5-DFS than high TSR ( P  = 0.000). Similar results were also obtained in patients with triple-negative breast cancer, human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and luminal–HER2-negative breast cancer. Conclusion TSR is an independent predictor for 5-DFS in breast cancer with worse survival outcomes in low TSR. The prognostic value of TSR was also observed in other three molecular subtypes.

Background This study aims to analyze potential differences in clinicopathology, efficacy of neoadjuvant therapy (NAT), and clinical outcome among HER2-null, HER2-ultralow and HER2-low breast cancers. Methods Consecutive cases of HER2-negative breast cancer that received NAT were included. They were classified as HER2-null (no staining), HER2-ultralow (incomplete faint staining in ≤ 10% of tumour cells) and HER2-low (HER2-1 + or HER2-2+, in situ hybridisation negative). Subgroup analysis was performed based on the HER2 expression level. Results Out of 302 patients, 215 (71.19%) were HER2-low, 59 (19.54%) were HER2-ultralow, and 28 (9.27%) were HER2-null. In comparison to the HER2-ultralow group, the HER2-low group exhibited higher expression frequencies of ER ( p  < 0.001), PR ( p  < 0.001), and AR ( p  = 0.004), along with a greater prevalence of the luminal subtype ( p  < 0.001). The HER2-ultralow group also demonstrated a higher prevalence of lymph node metastasis compared to the HER2-null group ( p  = 0.026). Varied rates of pathologic complete response (pCR) were observed among the three subgroups: HER2-null, HER2-ultralow, and HER2-low, with rates of 35.71%, 22.03%, and 12.56%, respectively. Only the HER2-low subgroup exhibited a significant difference compared to HER2-null ( p  = 0.001). Despite variations in pCR rates, the three subgroups exhibited comparable disease-free survival (DFS) ( p  = 0.571). Importantly, we found HER2-low patients with better treatment response (RCB-0/I) exhibited significantly better DFS than those with significant residual disease (RCB-II/III) ( P  = 0.036). The overall rate of HER2 immunohistochemical score discordance was 45.24%, mostly driven by the conversion between HER2-0 and HER2-low phenotype. Notably, 32.19% of cases initially classified as HER2-0 phenotype on baseline biopsy were later reclassified as HER2-low after neoadjuvant therapy, and it is noteworthy that 22 out of these cases (78.57%) originally had an HER2-ultralow status in the pretreatment biopsy sample. Conclusions Our results demonstrate the distinct clinicopathological features of HER2-low and HER2-ultralow breast tumors and confirm that RCB is an effective predictor of prognosis in HER2-low populations for the first time. Notably, our findings demonstrate high instability in both HER2-low and HER2-ultralow expression from the primary baseline biopsy to residual disease after NAT. Furthermore, this study is the first to investigate the clinicopathological feature and the effectiveness of NAT for HER2-ultralow breast cancer.

Breast cancer has become the most prevalent malignant tumor among women globally, posing a serious threat to women's life and health. Neoadjuvant therapy (NAT) has emerged as one of the standard treatment approaches for breast cancer patients. However, due to varying responses to NAT among different patients, significant differences in treatment effectiveness occur, impacting the timely alteration of treatment strategies for patients. This study included a total of 201 breast cancer patients who completed NAT, divided into a training group of 140 cases and a validation group of 61 cases. Based on clinical and pathological characteristics along with the Residual Cancer Burden (RCB) score, we utilized a support vector machine (SVM) algorithm to construct a Pathomics Breast Cancer Signature (PBCS) prediction model. We thoroughly validated the PBCS and compared it to a Pathomics Signature (PS) prediction model. In our study, we used CellProfiler to extract nine pathological features highly correlated with patients' RCB scoring from HE-stained slides of breast cancer NAT. Employing the SVM algorithm, we developed a pathological prediction label, named PS. Subsequently, through univariate and multivariate analysis, we discovered a significant correlation between HER2 and the patients' RCB scores. Integrating HER2 into PS, we constructed a breast cancer pathological prediction model, named PBCS. PBCS exhibits good performance in predicting the effectiveness of postoperative therapy (RCB 0-I) in both the training sets (AUC = 0.86 [95% CI: 0.7988-0.9173]) and validation sets (AUC = 0.83 [95% CI: 0.7219-0.9382]). In the validation set, PBCS significantly outperforms the PS (AUC = 0.65 [95% CI: 0.5121-0.7886]). Calibration curves and clinical decision curves also strongly support PBCS's ability to effectively predict the efficacy of therapy (RCB 0-I). PBCS can assist clinical and pathological physicians in accurately predicting patients' post-treatment RCB grading before initiating NAT. This offers a new approach to forecast breast cancer patients' responsiveness to NAT, aiding in devising personalized treatment strategies for patients.

Immunotherapy plays a key role in cancer treatment, however, responses are limited to a small number of patients. The biological basis for the success of immunotherapy is the complex interaction between tumor cells and tumor immune microenvironment (TIME). Historically, research on tumor immune constitution was limited to the analysis of one or two markers, more novel technologies are needed to interpret the complex interactions between tumor cells and TIME. In recent years, major advances have already been made in depicting TIME at a considerably elevated degree of throughput, dimensionality and resolution, allowing dozens of markers to be labeled simultaneously, and analyzing the heterogeneity of tumour-immune infiltrates in detail at the single cell level, depicting the spatial landscape of the entire microenvironment, as well as applying artificial intelligence (AI) to interpret a large amount of complex data from TIME. In this review, we summarized emerging technologies that have made contributions to the field of TIME, and provided prospects for future research.

This study aims to observe the clinical efficacy and safety of rigid gas permeable corneal contact lenses (RGP-CLs) wearing after femtosecond laser-assisted minimally invasive lamellar keratoplasty (FL-MILK) in progressive and advanced keratoconus eyes. Twenty-five patients (27 eyes) fitted with RGP-CLs after FL-MILK were enrolled, and 22 grading-matched keratoconus patients (23 eyes) as a control group. Corneal morphological data, diopter, best corrected vision, corneal endothelium, non-invasive tear film rupture time (NIBUT), corneal perception and comfort questionnaire were analysed before and after wearing RGP-CLs. In the FL-MILK group, the flat K, steep K and Kmax of the corneal anterior surface were decreased by 3.05D, 3.48D and 7.17D respectively after surgery ( P  = 0.011, 0.004 and 0.007). The central corneal thickness increased by 175.29 μm ( P  < 0.001). The basic curve of RGP-CLs after surgery was about 0.23 mm flatter than that before surgery ( P  = 0.013). There was no statistical difference in the best corrected vision and the comfort of wearing RGP-CLs before and after FL-MILK ( P  = 0.923, 0.391). Compared with the control group, there was no significant difference in vision improvement by RGP-CLs ( P  = 0.669). During the follow-up, the comfort of wearing RGP-CLs in the two groups was good, and no obvious adverse events were observed. This study showed MILK significantly increases corneal thickness and flattens corneal curvature, achieving good RGP-CLs corrected vision.

Enhanced ribosome biogenesis and protein synthesis are required for cell proliferation. During hematopoietic regeneration, hematopoietic stem cells (HSCs) proliferate rapidly to replenish the hematopoietic system. How HSCs respond and regulate ribosome biogenesis and protein synthesis during regeneration remains unclear. Here, we analyzed the expression of a series of ubiquitin-specific-proteases (USPs) during HSC regeneration. We found USP4 expression is significantly increased in proliferating HSCs. Further functional and mechanistic investigations revealed a crucial regulatory function of USP4 in HSC regeneration and leukemia progression by modulating ribosome biogenesis and protein synthesis. USP4 deubiquitinates and stabilizes PES1 to facilitate ribosome biogenesis and protein synthesis in proliferative HSCs and leukemic cells. Usp4 deletion significantly decreases protein synthesis, proliferation and reconstitution capacity of HSCs. Usp4 inhibition suppresses ribosome biogenesis and proliferation of leukemic cells, and prolongs the survival of AML (Acute myeloid leukemia) mice. These findings provide a new insight into the response mechanism of ribosome biogenesis and protein synthesis in HSCs, and their contribution to leukemia progression.

Excessive protein synthesis upon enhanced cell proliferation frequently results in an increase of unfolded or misfolded proteins. During hematopoietic regeneration, to replenish the hematopoietic system, hematopoietic stem cells (HSCs) are activated and undergo a rapid proliferation. But how the activated HSCs respond to the proliferation pressure is still ambiguous; The proper control of the functional reservoir in the activated HSCs remains poorly understood. Here, we show a significant upregulation of EVA1A protein associated with the increase of ER stress during hematopoietic regeneration. Deletion of Eva1a significantly enhances the regeneration capacity of HSCs by inhibiting the ER stress-induced apoptosis. Mechanistically, the expression of EVA1A protein was upregulated by CHOP, and thereby promoted the ER-mitochondria interlinking via MCL1, which resulted in mitochondria-mediated apoptosis. These findings reveal a pathway for ER stress responses of HSCs by the EVA1A mediated apoptosis, which play an important role in HSCs regeneration.

Fe 3 Al combines with steel to form bimetallic metal can benefit from steel’s mechanical strength and make full use of Fe 3 Al’s excellent performance under high temperatures. However, due to the poor fluidity and wettability of liquid Fe 3 Al to steel, the cladding prepared by traditional linear welding is not available to industrial sector. Hence, to optimize preparation, an arc deposition procedure based on a weaving path is proposed. Fe 3 Al cladding was prepared on the steel with weaving and linear paths by arc deposition technology, respectively, and the characteristics of the cladding were compared in terms of formability, surface feature and microstructure. The results demonstrated that the cladding prepared by weave arc deposition had better formability, lower dilution rates and fewer defects than that by the line one. Compared with the image captured by high-speed camera, the substantial difference was attributed to the higher molten pool velocities, which led to a smaller volume of molten pool in weave process. Under this circumstance, the arc force was conducive to the spread of liquid metal, forming a relatively small contact angle (< 45°). The finite element analysis revealed that the temperature distribution and thermal cycles resulted in finer grains in the weave process; furthermore, the weave process produced less residual stress, causing an increment of 153% in bonding strength between the cladding and the steel, compared to linear sample. Overall, the weave arc deposition technology is capable of molding Fe 3 Al layers efficiently and offers a good prospect for applications.

Background To evaluate the long-term effectiveness of orthokeratology (ortho-K) lenses with small treatment zone (STZ) or conventional treatment zone (CTZ) in controlling axial elongation in children with myopia as well as the impact on visual quality. We also sought to determine the effect of retinal visual signal quality on axial elongation. Methods This is a prospective randomized controlled study. A total of 140 participants (age ranging from 8 to 12 years) were randomly assigned to wear either STZ or CTZ ortho-K lenses. STZ ortho-K lenses design was achieved by changing the depth of reverse zone and the sagitta height of the optical zone. Using the IOL-Master 500, axial length (AL) was measured at baseline and after 6, 12 and 18 months of ortho-K treatment. Spherical aberration (SA) and corneal topographic parameters were obtained by the Pentacam anterior segment analyzer at baseline and the 1-month follow-up visit, and optical qualities were assessed by optical quality analysis system-II (OQAS-II) at baseline and after 1 month of lens wearing. Optical quality parameters mainly included the modulation transfer function (MTF) cutoff, Strehl ratio (SR), objective scattering index (OSI), and predicted visual acuity (PVA). Results A total of 131 participants completed the study, including 68 in the STZ group and 63 in the CTZ group. The STZ group had significantly reduced AL elongation compared to the CTZ group after treatment (12 months: 0.07 ± 0.11 mm vs. 0.14 ± 0.12 mm, P  = 0.002; 18 months: 0.17 ± 0.15 mm vs. 0.26 ± 0.16 mm, P  = 0.002). The topography in the STZ group showed a smaller treatment zone (TZ) diameter (2.50 ± 0.23 mm vs . 2.77 ± 0.18 mm, P  < 0.001), a wider defocus ring width (2.45 ± 0.28 mm vs. 2.30 ± 0.30 mm, P  = 0.006), and larger values of total amount of defocus (119.38 ± 63.71 D·mm 2 vs. 91.40 ± 40.83 D·mm 2 , P  = 0.003) and total SA (0.37 ± 0.25 μm vs . 0.25 ± 0.29 μm, P  = 0.015), compared with the CTZ group. Objective visual quality decreased in both groups ( P  < 0.001). This was evidenced by a greater decrease in MTF cutoff (− 14.24 ± 10.48 vs. − 10.74 ± 9.46, P  = 0.047) and SR values (− 0.09 ± 0.07 vs. − 0.06 ± 0.07, P  = 0.026), and an increase in OSI value (0.84 ± 0.72 vs. 0.58 ± 0.53, P  = 0.019). PVA9% decreased significantly in the STZ group but not the CTZ group. A statistically significant negative correlation was found between the changes in total SA and MTF cutoff values ( r  =  − 0.202, P  = 0.025). AL changes were associated with sex, change of MTF cutoff value, increment of total SA and TZ area. Conclusions Compared with CTZ ortho-K lenses, STZ ortho-K lenses significantly inhibited axial elongation in children with myopia while moderately reducing their objective visual quality. Axial elongation was affected by retinal visual quality, and it may be a possible mechanism for ortho-K slowing myopia progression. Trial registration This trial is registered at Chinese Clinical Trial Registry on November 5, 2019 with trial registration number: ChiCTR1900027218. https://www.chictr.org.cn/showproj.html?proj=45380