[Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer].

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

Application and prognostic relevance of CD34 detection in immunophenotyping of pediatric acute B lymphoblastic leukemia.

OBJECTIVE: We aimed to investigate the application of CD34 detection in immunophenotypic discrimination and its prognostic relevance in children with acute B-lymphoblastic leukemia (B-ALL). PATIENTS AND METHODS: A retrospective analysis was conducted on clinical follow-up data of 105 children with newly diagnosed B-ALL treated at our hospital from January 2022 to December 2023. Based on the expression of CD34 in the bone marrow, patients were divided into a CD34 positive group (positive cells ≥10%) and a CD34 negative group (positive cells <10%). The study compared the positive rates of common leukemia cell antigens, clinical characteristics, initial treatment responses, and long-term follow-up outcomes between the two groups. RESULTS: Among all 105 B-ALL cases, 87 children (82.9%) had bone marrow CD34 positive cells ≥10%, classified into the CD34 positive group, while the remaining 18 children (17.1%) had bone marrow CD34 positive cells <10%, classified into the CD34 negative group. The CD34 positive group exhibited significantly higher positive rates of CD13 expression, standard-risk B-ALL, and risk stratification than the CD34 negative group. In contrast, the proportions of early pre-B-ALL, E2A-PBX1 fusion gene, and MLL-AF4 fusion gene were significantly lower in the CD34 negative group, with statistically significant differences (p<0.05). No significant differences were found in the positive rates of leukemia cell antigens such as CD10, CD19, CD20, CD22, CD79a, CD13, CD33, and CD38 between the two groups (p>0.05). The occurrence rates of minimal residual disease (MRD) and relapse after induction chemotherapy in the CD34 positive group were significantly lower than those in the CD34 negative group (p<0.05). However, the sensitivity to the first prednisone treatment and bone marrow treatment efficacy on the 19th and 33rd days after chemotherapy showed no significant differences between the groups (p>0.05). CONCLUSIONS: A higher positive rate of bone marrow CD34 expression in children with B-ALL is associated with a favorable prognosis. Children with negative CD34 expression are relatively more prone to MRD and tumor relapse after chemotherapy.

[Screening of differentially expressed genes in gastric cancer based on GEO database and function and pathway enrichment analysis].

OBJECTIVE: To explore the core genes related to the diagnosis and prognosis of gastric cancer (GC) based on Gene Expression Omnibus (GEO) database and screen the molecular targets involved in the occurrence and development of GC. METHODS: GC microarray data GSE118916, GSE54129 and GSE79973 were downloaded from GEO database, and the differentially expressed genes (DEGs) were screened. Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks (PPI) were constructed to identify the hub genes, whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA. The expression levels of these core genes were also detected in different GC cell lines using qRT- PCR. RESULTS: Seventy-seven DEGs were identified, which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand, involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion. Nine hub genes were obtained, among which SPARC, TIMP1, THBS2, COL6A3 and THY1 were significantly up- regulated and TFF1, GKN1, TFF2 and PGC were significantly down-regulated in GC. The abnormal expressions of SPARC, TIMP1, THBS2, COL6A3, TFF2 and THY1 were significantly correlated with the survival time of GC patients. ROC curve analysis showed that aberrant expression of TIMP1 SPARC, THY1 and THBS2 had high diagnostic value for GC. High expressions of SPARC, TIMP1, THBS2 and COL6A3 were detected in GC tissues. In the GC cell lines, qRT- PCR revealed different expression patterns of these hub genes, but their expressions were largely consistent with those found in bioinformatics analyses. CONCLUSION: SPARC, TIMP1, THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Ambulatory facial feminization surgery: a comparative analysis of outcomes and complications.

BACKGROUND: To date, there are no studies investigating the safety and outcomes of facial feminization surgery (FFS) as an outpatient procedure. This is the first study of its kind analyzing the outcomes of ambulatory FFS based on a comparison of complications, post-operative emergency department or urgent care (ED/UC) visits, and readmissions between patients who underwent FFS with admission versus same-day surgery. METHODS: A retrospective analysis was conducted on all patients who underwent FFS in a single integrated healthcare system. Patient charts were reviewed for operative details, complications, post-operative ED/UC visits, readmission, and demographic factors. Major outcomes including complications, readmissions, and ED/UC visits were compared between groups with same-day discharge and post-operative hospital admission. RESULTS: Of 242 patients included in the study, ED/UC visits were comparable between patients discharged same-day (18.2%) and patients admitted post-operatively (21.6%, p = 0.52). Logistic regression showed no significant difference in the composite outcomes of minor complications, major complications, and readmissions (15.6% for ambulatory versus 19.3% for admission, p = 0.46). Temporary nerve palsy, infection, and hematoma were the most common post-operative complications. However, covariates of a lower face procedure and operative time were shown to have significant differences in the composite complication outcome (p = 0.04 and p = 0.045, respectively). CONCLUSION: Ambulatory FFS is a safe practice with no associated increase in adverse outcomes including complications, ED/UC visits, and readmission when compared to post-operative admission. Adoption of same-day FFS should be considered by high-volume gender health centers to potentially benefit from increased scheduling flexibility and efficiency, increased access to care, and lower healthcare costs.

A Cholecystokinin Analogue Ameliorates Cognitive Deficits and Regulates Mitochondrial Dynamics via the AMPK/Drp1 Pathway in APP/PS1 Mice.

BACKGROUND: There are no drugs on the market that can reverse or slow Alzheimer's disease (AD) progression. A protease-resistant Cholecystokinin (CCK) analogue used in this study is based on the basic structure of CCK, which further increases the stability of the peptide fragment and prolongs its half-life in vivo. We observed a neuroprotective effect of CCK-8L in APPswe/PS1dE9 (APP/PS1) AD mice. However, its corresponding mechanisms still need to be elucidated. OBJECTIVE: This study examined CCK-8L's neuroprotective effects in enhancing cognitive impairment by regulating mitochondrial dynamics through AMPK/Drp1 pathway in the APP/PS1 AD mice. METHODS: Behavioural tests are applied to assess competence in cognitive functions. Transmission electron microscopy (TEM) was performed to observe the ultrastructure of mitochondria of hippocampal neurons, Immunofluorescent staining was employed to assay for Aß1-42, APP, Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and dynamin-related protein1 (Drp1). CRISPR/Cas9 was utilized for targeted knockout of the CCKB receptor (CCKBR) in the mouse APP/PS1 hippocampal CA1 region. A model of lentiviral vector-mediated overexpression of APP in N2a cells was constructed. RESULTS: In vivo, experiments revealed that CCK analogue and liraglutide significantly alleviated cognitive deficits in APP/PS1 mice, reduced Aß1-42 expression, and ameliorated l damage, which is associated with CCKBR activation in the hippocampal CA1 region of mice. In vitro tests showed that CCK inhibited mitochondrial fission and promoted fusion through AMPK/Drp1 pathway. CONCLUSIONS: CCK analogue ameliorates cognitive deficits and regulates mitochondrial dynamics by activating the CCKB receptor and the AMPK/Drp1 pathway in AD mice.

Interaction of smoking and aging on emphysema and small airways disease in asymptomatic healthy men by CT-based parametric response mapping analysis.

AIM: To explore whether small airway disease and emphysema were affected by the interaction between smoking and aging on chest computed tomography (CT) images of asymptomatic healthy men analysed using a quantitative imaging tool parametric response mapping (PRM). MATERIALS AND METHODS: In this retrospective study, 95 asymptomatic healthy men underwent biphasic chest CT. The PRM classifies lung as a percentage of normal (PRMNormal%), functional small airway disease (PRMfSAD%), and emphysema (PRMEmph%). The patients were divided into groups based on their age and smoking status. Multiple linear regression analysis was applied to explore the factors influencing lung injury. Simple effects analysis was performed to explore the interaction between different age groups and smoking status. RESULTS: The interaction between aging and smoking significantly affected PRMfSAD% and PRMEmph% (p<0.001). The age range 60-69 and smoking were associated with increased PRMfSAD% and PRMEmph% (p<0.05). Futher stratification into different age subgroups showed that smoking was associated with increased PRMfSAD% and PRMEmph% in the 50-59 year age group. Besides, smoking in the 50-59 and 60-69 years group was associated with decreased PRMNormal%, while smoking in the 60-69 years group did not significantly influence the prevalence of PRMfSAD% and PRMEmph% (p>0.05). CONCLUSIONS: PRM reveals the interplay between smoking and aging in the development of lung injury in asymptomatic healthy men. Aging and smoking are important factors of emphysema and small airway disease in the 50-69 years group. In the 60-69 years group, aging poses a greater risk of lung injury compared to smoking.

[Epidemiological investigation of constipation in urban areas of Hangzhou, China].

Objective: To determine the prevalence and risk factors of constipation in Hangzhou urban areas by analyzing data from a recent epidemiological survey. Methods: From August 2022 to June 2023, a cross-sectional survey was conducted on 43 communities on eight streets in suburbs of Hangzhou, including Wangjiang, Sijiqing, Puyan, Changhe, Ziyang, Xiaoshanchengxiang, Zhuantang, and Banshan. Written questionnaires were filled out face to face by community doctors. The prevalence of constipation was investigated using a combination of the Bristol stool typing method and the Rome IV criteria. The risk factors for constipation were analyzed using multivariate logistic regression analysis. Results: The study cohort comprised 10,479 participants, 5551 of whom were male (53.0%) and 4928 female (47.0%). The overall prevalence of constipation was 10.6% (1107/10,479). The prevalence was 11.0% (613/5551) for male and 10.0% (494/4928) for female participants; this difference is not statistically significant (P>0.05).There were no significant differences in the prevalence of constipation between different categories of body mass index (P>0.05). The prevalence of constipation was highest in individuals aged 70 years and above, accounting for 15.4% (264/1717) of all cases. There were significant differences in the prevalence of constipation between different occupations, marital statuses, and educational levels (P<0.001). Patients with hypertension or diabetes mellitus had a higher prevalence of constipation than those without these conditions, those who had been taking long-term medication had a higher prevalence of constipation than those who did not, parents of children with constipation had a higher prevalence of constipation than those with children who did not have constipation, and there were other significant differences in various variables (P<0.001). Multivariate logistic regression analysis of modifiable factors revealed that eating less fruit (OR=1.284, 95%CI: 1.061-1.553, P=0.010), liking spicy and salty food (OR=1.234, 95%CI: 1.039-1.466, P=0.016), sleeping for too long (OR=1.644, 95%CI: 1.260-2.144, P<0.001), irregular sleep patterns (OR=1.370, 95%CI: 1.127-1.665, P=0.002) and minimal exercise (OR=1.388, 95% CI: 1.168-1.649, P<0.001) were all risk factors for constipation; whereas mix diets (OR=0.709,95%CI:0.608-0.826, P<0.001), meat diets (OR=0.604,95%CI: 0.495-0.736, P<0.001), moderate alcohol consumption (OR=0.659, 95% CI: 0.534-0.812, P<0.001), less or no drinking (OR=0.523, 95% CI: 0.428-0.638, P<0.001), and non-smoking (OR=0.819, 95%CI:0.674-0.995, P<0.001) protected against constipation. We found no association between dietary preferences and the risk of constipation (refined grains: OR=1.147, 95%CI:0.944-1.393, P=0.167; no specific preference: OR=0.935, 95%CI:0.783-1.117, P=0.459). The rate of agreement between self-evaluation of constipation by the respondents and objective criteria was higher for negatives (95.8%) than for positives (38.0%). Conclusion: The prevalence of constipation is relatively high in the urban population of Hangzhou. A good lifestyle and diet can significantly reduce its incidence. There should be more emphasis on preventive education, promotion of prevention of constipation, and advocacy for a healthy lifestyle.

[Establishment and validation of nomogram prediction model for complicated acute appendicitis].

Objective: To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA). Methods: The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged (M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Results: The elderly (age≥60 years) (OR=2.428, 95%CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) (OR=1.089, 95%CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) (OR=1.122, 95%CI: 1.078 to 1.168), total bilirubin (every rise of 1 µmol/L) (OR=2.629, 95%CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95%CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion: The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.

[Incidence and related factors of chronic neuropathic pain in elderly patients after video-assisted thoracoscopic surgery].

Objective: To investigate the incidence and related factors of chronic neuropathic pain (CNP) in elderly patients after thoracoscopic surgery. Methods: A total of 463 elderly patients (aged≥60 years) who underwent elective video-assisted thoracoscopic surgery from November 2020 to May 2021 at Peking Union Medical College Hospital were prospectively recruited. Among them, 283 were males and 180 were females, with an average age of (66.6±4.8) years. Chronic postsurgical pain (CPSP) was assessed by telephone at 6 months after surgery, and then the patients with CNP were screened using the ID-pain scale. Multivariable logistic regression was used to analyze the related factors for CNP in elderly patients after thoracoscopic surgery. Results: The incidence of CPSP was 41.9% (194/463), and the incidence of CNP was 18.8% (87/463). Multivariable logistic regression analysis showed that incision number<3 (OR=0.385, 95%CI: 0.156-0.949, P=0.038) and intraoperative N2O inhalation (OR=0.506, 95%CI: 0.304-0.842, P=0.009) were protective factors for CNP in elderly patients after thoracoscopic surgery, but high numeric rating scale (NRS) score on the first day after surgery (OR=1.180, 95%CI: 1.056-1.318, P=0.003) was a risk factor. Conclusions: The incidence of CNP in elderly patients after thoracoscopic surgery is 18.8%. Incision number<3 and intraoperative N2O inhalation are protective factors for CNP, but high NRS score on the first day after surgery is a risk factor.

[Applications of anterior segment optical coherence tomography in corneal refractive surgery].

Anterior segment optical coherence tomography (AS-OCT) has the characteristics of non-contact, noninvasive, high sensitivity, and repeatability, and offers high-resolution in vivo imaging of the structures of the anterior eye segment. It can be used in the diagnosis and assistance of conditions related to the anterior eye segment. This review provides an update on the research and clinical applications of AS-OCT in corneal refractive surgery, including preoperative keratoconus screening, intraoperative real-time visualization of corneal structures, postoperative corneal evaluation, and management of postoperative complications. We also explore the potential application of AS-OCT in combination with corneal biomechanical detection for corneal refractive surgery.

The value of MRI in predicting hepatocellular carcinoma with cytokeratin 19 expression: a systematic review and meta-analysis.

AIM: To evaluate the overall diagnostic performance of magnetic resonance imaging (MRI), different image features, and different image analysis methods in predicting hepatocellular carcinoma (HCC) with cytokeratin 19 (CK19) expression. MATERIALS AND METHODS: A systematic literature search was performed to identify studies using MRI to predict HCC with CK19 expression between 2012 and 2023. Data were extracted to calculate the pooled sensitivity and specificity. Overall diagnostic performance was assessed using areas under the summary receiver operating characteristic curve (AUC). Subgroup analyses were conducted for specific image features and according to image analysis methods (traditional image feature, radiomics, and combined methods). Z-test statistics was used to analyse the differences in diagnostic performance between combined and individual methods. RESULTS: Eleven studies with 14 datasets (1,278 lesions from 1,264 patients) were included. The overall pooled sensitivity, specificity, and AUC with corresponding 95% confidence intervals were estimated to be 0.72 (0.55, 0.85), 0.88 (0.80, 0.93), and 0.89 (0.86, 0.91) for MRI in predicting HCC with CK19 expression. Combined methods had higher sensitivity than image feature methods (0.86 versus 0.54, p=0.001), with no difference in specificity (0.85 versus 0.87, p=0.641). There were no significant differences between radiomics and combined methods regarding sensitivity (p=0.796) and specificity (p=0.535), respectively. CONCLUSION: MRI shows moderate sensitivity and high specificity in identifying HCC with CK19 expression. The application of radiomics can improve the sensitivity of MRI in identifying HCC with CK19 expression.

[Rediscussion on hot issues of endocrine therapy for breast cancer].

In the past decade, generated data of large-scale clinical research of endocrine therapy and the update of guidelines have changed clinical practice of breast cancer treatment. However, there are unresolved issues on endocrine therapy. Based on new evidences and clinical experience, we expounded our points on neoadjuvant endocrine therapy, CDK4/6 inhibitoradjuvant therapy, concepts of endocrine sensitivity and endocrine resistance, first-line treatment for metastatic breast cancer, treatment options after progression on CDK4/6 inhibitor and treatment ofvisceral crisis.

Study on early markers of death in patients with COVID-19.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) was first discovered in December 2019, and since then rapidly spread worldwide. Our study aimed to investigate the early indicators of death in patients suffering from severe and critical COVID-19. PATIENTS AND METHODS: A retrospective cohort study was conducted on patients with severe and critical COVID-19, admitted to the Seventh Hospital of Wuhan. Clinical information was collected from electronic medical records according to standardized data collection tables. Patients were divided into non-survival and survival groups based on the disease outcome. Using univariate and multivariate logistic regression analysis, and calculating odds ratios (OR) and 95% confidence intervals (CI), independent risk factors for death in severe and critically ill COVID-19 patients were identified. RESULTS: The median age of 162 patients (57.4% males) was 67.5 years old. Patients in the non-survival group had significantly higher white blood cell count, decreased lymphocyte count, anemia and thrombocytopenia compared to patients in the survival group (p < 0.05). A 28-day mortality rate of the study cohort was 31.5%. Multivariate logistic regression analysis showed that underlying heart disease, lymphocyte count < 1.0 × 109/L, glomerular filtration rate < 66, lactate > 2.2 mmol/L, higher Sequential Organ Failure Assessment (SOFA) score, lower oxygenation index (OR 1.748; 95% CI 1.024-2.984; p=0.041) and higher "multi-lobar infiltration, hypo lymphocytosis, bacterial co-infection, smoking history, hypertension and age" (MuLBSTA) score (OR 1.601; 95% CI 1.062-2.415; p=0.025) were risk factors associated with death in patients with severe and critical COVID-19. CONCLUSIONS: Underlying heart disease, lymphocyte count, glomerular filtration rate, lactate, oxygenation index, SOFA score, and MuLBSTA score were associated with the risk of death in severe and critical COVID-19 patients.

HER2-low expression in patients with advanced or metastatic solid tumors.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low is a newly defined category with HER2 1+ or 2+ expression by immunohistochemistry (IHC) and lack of HER2 gene amplification measured by in situ hybridization (ISH). Much remains unknown about the HER2-low status across tumor types and changes in HER2 status between primary and metastatic samples. PATIENTS AND METHODS: HER2 expression by IHC was evaluated in 4701 patients with solid tumors. We have evaluated the HER2 expression by IHC and amplification by ISH in paired breast and gastric/gastroesophageal (GEJ) primary and metastatic samples. HER2 expression was correlated with ERBB2 genomic alterations evaluated by next-generation sequencing (NGS) in non-breast, non-gastric/GEJ samples. RESULTS: HER2 expression (HER2 IHC 1-3+) was found in half (49.8%) of the cancers, with HER2-low (1 or 2+) found in many tumor types: 47.1% in breast, 34.6% in gastric/GEJ, 50.0% in salivary gland, 46.9% in lung, 46.5% in endometrial, 46% in urothelial, and 45.5% of gallbladder cancers. The concordance evaluation of HER2 expression between primary and metastatic breast cancer samples showed that HER2 3+ remained unchanged in 87.1% with a strong agreement between primary and metastatic samples, with a weighted kappa (Κ) of 0.85 (95% confidence interval 0.79-0.91). ERBB2 alterations were identified in 117 (7.5%) patients with non-breast, non-gastric/GEJ solid tumors who had NGS testing. Of 1436 patients without ERBB2 alterations, 512 (35.7%) showed any level HER2 expression by IHC. CONCLUSION: Our results show that HER2-low expression is frequently found across tumor types. These findings suggest that many patients with HER2-low solid tumors might benefit from HER2-targeted therapies.

Preoperative prediction of microvascular invasion and perineural invasion in pancreatic ductal adenocarcinoma with 18F-FDG PET/CT radiomics analysis.

AIM: To develop and validate a predictive model based on 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) radiomics features and clinicopathological parameters to preoperatively identify microvascular invasion (MVI) and perineural invasion (PNI), which are important predictors of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Preoperative 18F-FDG PET/CT images and clinicopathological parameters of 170 patients in PDAC were collected retrospectively. The whole tumour and its peritumoural variants (tumour dilated with 3, 5, and 10 mm pixels) were applied to add tumour periphery information. A feature-selection algorithm was employed to mine mono-modality and fused feature subsets, then conducted binary classification using gradient boosted decision trees. RESULTS: For MVI prediction, the model performed best on a fused subset of 18F-FDG PET/CT radiomics features and two clinicopathological parameters, with an area under the receiver operating characteristic curve (AUC) of 83.08%, accuracy of 78.82%, recall of 75.08%, precision of 75.5%, and F1-score of 74.59%. For PNI prediction, the model achieved best prediction results only on the subset of PET/CT radiomics features, with AUC of 94%, accuracy of 89.33%, recall of 90%, precision of 87.81%, and F1 score of 88.35%. In both models, 3 mm dilation on the tumour volume produced the best results. CONCLUSIONS: The radiomics predictors from preoperative 18F-FDG PET/CT imaging exhibited instructive predictive efficacy in the identification of MVI and PNI status preoperatively in PDAC. Peritumoural information was shown to assist in MVI and PNI predictions.

Raspberry ketone glucoside suppresses melanin synthesis through IL6/JAK1/STAT3 signal pathway.

OBJECTIVE: This study aimed to evaluate the anti-melanogenic activity of raspberry ketone glucoside (RKG) and further explore the specific molecular mechanisms by which RKG affects melanogenesis. MATERIALS AND METHODS: The B16F10 cells model, the mushroom tyrosinase model and the zebrafish model were used to assess the whitening activity of RKG. We subsequently identified possible pathways related to RKG inhibition of melanogenesis by RNA-seq analysis and qRT-PCR on the zebrafish model, and further explored the effects of key genes on the pathway on the melanogenic effect of RKG by using related pathway inhibitors and Tg [mpeg: EGFP] transgenic zebrafish line. RESULTS: RKG could noticeably inhibit melanogenesis in B16F10 cells in vitro and on zebrafish in vivo. The RNA-Seq analysis and the qRT-PCR in zebrafish embryos indicated that the inhibition of melanogenesis by RKG could be achieved by activating JAK1/STAT3 signal pathway and inhibiting the expression levels of the MITFa, TYR, TYRP1a genes directly associated with melanogenesis. The inhibitor tests revealed that the inhibitory effect of the RKG on melanogenesis was restored by the IL6, JAK1/2, and STAT3 inhibitors, specifically STAT3 inhibitor. We further examine the relationship between the JAK1/STAT3 signal pathway and the MITFa. The achieved results indicate that the RKG could activate the zebrafish macrophages via the JAK1, but the inhibition of macrophage activation by loganin did not affect the anti-pigmentation effect of the RKG. CONCLUSIONS: RKG showed remarkable whitening activity on both B16F10 cells in vitro and zebrafish model in vivo. Furthermore, RKG could inhibit melanogenesis by activating the IL6/JAK1/STAT3 pathway, inhibiting the transcriptional activity of MITFa, and its downstream expression levels of the TYR and TYRP1a genes.

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.