Spatially Confined π-Complexation within Pore-Space-Partitioned Metal-Organic Frameworks for Enhanced Light Hydrocarbon Separation and Purification.

Ultramicroporous metal-organic frameworks (MOFs) are demonstrated to be advantageous for the separation and purification of light hydrocarbons such as C2H2, C2H4, and CH4. The introduction of transition metal sites with strong π-complexation affinity into MOFs is more effective than other adsorption sites for the selective adsorption of π-electron-rich unsaturated hydrocarbon gases from their mixtures. However, lower coordination numbers make it challenging to produce robust MOFs directly utilizing metal ions with π-coordination activity, such as Cu+, Ag+, and Pd2+. Herein, a series of novel π-complexing MOFs (SNNU-33s) with a pore size of 4.6 Å are precisely constructed by cleverly introducing symmetrically matched C3-type [Cu(pyz)3] (pyz = pyrazine) coordinated fragments into 1D hexagonal channels of MIL-88 prototype frameworks. Benifit from the spatial confinement combined with π-complex-active Cu+ of [Cu(pyz)3], pore-space-partitioned SNNU-33 MOFs all present excellent C2H2/CH4, C2H4/CH4, and CO2/CH4 separation ability. Notably, the optimized SNNU-33b adsorbent demonstrates top-level IAST selectivity values for C2H2/CH4 (597.4) and C2H4/CH4 (69.8), as well as excellent breakthrough performance. Theoretical calculations further reveal that such benchmark light hydrocarbon separation and purification ability is mainly ascribed to the extra-strong binding affinity between Cu+ and π-electron donor molecules via a spatially confined π-complexation process.

Maternal Dietary Cholesterol and Egg Intake during Pregnancy and Large-for-Gestational-Age Infants: A Prospective Cohort Study.

BACKGROUND: Cholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversy over whether pregnant females should limit their cholesterol intake. OBJECTIVES: The objective of this study was to investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. METHODS: A total of 4146 mother-child pairs were included based on the Jiangsu Birth Cohort study. Maternal dietary information was assessed with a semiquantitative food-frequency questionnaire. Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. RESULTS: The median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase in birth weight z-score, with per standard deviation increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 [95% confidence interval (CI): 0.07, 0.25] and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters was positively linked to LGA, with an adjusted relative risk of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared with mothers consuming ≤7 eggs/wk in the third trimester, the adjusted relative risk for having an LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8-10 eggs/wk and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/wk (P-trend = 0.015). CONCLUSIONS: Maternal total dietary cholesterol intake, as well as consuming over 7 eggs/wk during pregnancy, displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.

Protein O-GlcNAcylation: The sweet hub in liver metabolic flexibility from a (patho)physiological perspective.

O-GlcNAcylation is a dynamic, reversible and atypical O-glycosylation that regulates various cellular physiological processes via conformation, stabilisation, localisation, chaperone interaction or activity of target proteins. The O-GlcNAcylation cycle is precisely controlled by collaboration between O-GlcNAc transferase and O-GlcNAcase. Uridine-diphosphate-N-acetylglucosamine, the sole donor of O-GlcNAcylation produced by the hexosamine biosynthesis pathway, is controlled by the input of glucose, glutamine, acetyl coenzyme A and uridine triphosphate, making it a sensor of the fluctuation of molecules, making O-GlcNAcylation a pivotal nutrient sensor for the metabolism of carbohydrates, amino acids, lipids and nucleotides. O-GlcNAcylation, particularly prevalent in liver, is the core hub for controlling systemic glucose homeostasis due to its nutritional sensitivity and precise spatiotemporal regulation of insulin signal transduction. The pathology of various liver diseases has highlighted hepatic metabolic disorder and dysfunction, and abnormal O-GlcNAcylation also plays a specific pathological role in these processes. Therefore, this review describes the unique features of O-GlcNAcylation and its dynamic homeostasis maintenance. Additionally, it explains the underlying nutritional sensitivity of O-GlcNAcylation and discusses its mechanism of spatiotemporal modulation of insulin signal transduction and liver metabolic homeostasis during the fasting and feeding cycle. This review emphasises the pathophysiological implications of O-GlcNAcylation in nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and hepatic fibrosis, and focuses on the adverse effects of hyper O-GlcNAcylation on liver cancer progression and metabolic reprogramming.

Assisted reproductive technology and neurodevelopment in children at 1 year of age: a longitudinal birth cohort study.

BACKGROUND: With remarkable advancements in assisted reproductive technology (ART), the number of ART-conceived children continues to increase. Despite increased research investigating the outcomes of ART children, evidence on neurodevelopment remains controversial. OBJECTIVE: The aim of this study was to investigate the association between ART use and neurodevelopment in children at 1 year of age and to determine whether the characteristics of parental infertility and specific ART procedures affect neurodevelopment in children. STUDY DESIGN: The Jiangsu Birth Cohort enrolled couples who received ART treatment and who conceived spontaneously (2014-2020) in Jiangsu Province, China. In this study, we included 3531 pregnancies with 3840 cohort children who completed neurodevelopment assessment at 1 year of age, including 1906 infants conceived by ART (including 621 twins). Poisson regressions were fitted to estimate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for ART use with neurodevelopmental outcomes (cognition, receptive communication, expressive communication, fine motor, and gross motor) in children. RESULTS: Among singletons, ART use was associated with a 24% to 34% decrease in the risk for noncompetent development in 3 domains (cognition, adjusted RR, 0.66; 95% CI, 0.53-0.82; receptive communication, 0.76; 0.64-0.91; expressive communication, 0.69; 0.51-0.93) after adjustment for conventional covariates. However, an inverse association was observed in the gross motor domain, with ART singletons having a greater risk of being noncompetent in gross motor development than their non-ART counterparts (adjusted RR, 1.41; 95% CI, 1.11-1.79). Compared with singletons, twins resulting from ART treatment demonstrated compromised neurodevelopment in several domains. Furthermore, we continued to observe that the transfer of 'poor' quality embryos was associated with greater risks for noncompetent development in receptive communication (adjusted RR, 1.50; 95% CI, 1.05-2.14) and gross motor domains (1.55; 1.02-2.36) among ART singletons. CONCLUSION: These results generally provide reassuring evidence among singletons born after ART in the cognition, communication, and fine motor domains, but drawn attention to their gross motor development. The quality of transferred embryos in ART treatment might be associated with offspring neurodevelopment; however, the potential associations warrant further validation in independent studies, and the clinical significance needs careful interpretation.

Clinical features of inflammatory bowel disease unclassified: a case-control study.

BACKGROUND: Approximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn's disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification. METHODS: The clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated. RESULTS: 60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification. CONCLUSIONS: IBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

Reproductive outcomes of single frozen-thawed embryo transfer in patients with endometriosis after preimplantation genetic testing.

PURPOSE: The reproductive outcomes of patients with endometriosis who are infertile have attracted recent attention. We aimed to explore whether endometriosis affects endometrial receptivity by observing pregnancy outcomes following a euploid blastocyst frozen embryo transfer. METHODS: This retrospective cohort study analyzed the data of patients with endometriosis from the reproductive hospital affiliated to Shandong University between January 2015 and December 2021. Control groups were matched using the 1:3 propensity score. The live birth, clinical pregnancy, biochemical pregnancy, clinical abortion, premature birth, and aneuploid rates were compared between the control group and endometriosis group. RESULTS: A total of 625 patients who underwent preimplantation genetic testing (PGT) prior to embryo implantation were included in the analysis. There were no significant differences in the live birth, clinical pregnancy, biochemical pregnancy, clinical abortion, and premature birth rates between the two groups. The aneuploidy rate of blastocysts obtained from the endometriosis group was higher than that of the control group (P = 0.012). CONCLUSION: Pregnancy outcomes using frozen embryos after PGT in patients with endometriosis did not differ from those in other women experiencing infertility. However, endometriosis may affect the quality of oocytes, resulting in a higher rate of aneuploidy.

Modulation of long noncoding RNAs by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review.

Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.

Characteristics of Clinical Isolates of Listeria monocytogenes in Sichuan, China, in 2022 Based on Whole Genome Sequencing Analysis.

Listeria monocytogenes is a foodborne pathogen. In 2022, we collected 15 strains of L. monocytogenes isolated from patients in some foodborne disease sentinel monitoring hospitals in Sichuan Province. Through whole genome sequencing (WGS), we obtained the virulence genes carried by the strains, multi-locus sequence typing (MLST), core genome MLST (cgMLST), clonal complex (CC), and serum groups and constructed a phylogenetic tree and minimum spanning tree with nonhuman strains. An analysis shows that all 15 strains of L. monocytogenes carry virulence genes LIPI-1 and LIPI-2, whereas the carrying rates of LIPI-3 and LIPI-4 virulence genes are relatively low. The MLST typing results showed a total of 10 sequence types (ST), including 10 CCs, with ST7 being the dominant type. The cgMLST clearly distinguishes strains of different lineages and CC types. The serum group is divided into three types: IIa, IIb, and IVb, with IIa being the dominant serum group. An analysis of antibiotic genes showed that all 15 strains carried FosX, lin, mprF, and norB with high carrying rates. The minimum inhibitory concentration results indicated that all were susceptible to eight antibiotics (ampicillin, penicillin, tetracycline, meropenem, erythromycin, vancomycin, ciprofloxacin, and trimethoprim-sulfamethoxazole). The analysis of strains isolated from different sources of Listeria revealed varying degrees of diversity, and the contamination of meat and environment within the province is closely related to clinical cases. L. monocytogenes isolated from clinical cases in Sichuan Province carry multiple virulence and antibiotic genes, with high potential pathogenicity. It is necessary to further strengthen the monitoring and control of food and environment by L. monocytogenes within Sichuan Province.

Molecular Characteristics of Staphylococcus aureus Isolates form Food-Poisoning Outbreaks (2011-2022) in Sichuan, China.

Staphylococcal food poisoning (SFP) is one of the most common foodborne diseases in the world. This study aimed to investigate the molecular epidemiological characteristics of Staphylococcus aureus isolated from SFP. A total of 103 S. aureus isolates were obtained during 2011-2022 in Sichuan, southwest China. All isolates were tested for the genomic characteristics and phylogenetic analysis by performing whole-genome sequencing. Multilocus sequence typing analysis showed 17 multilocus sequence types (STs), ST7 (23.30%), ST5 (22.33%), and ST6 (16.50%) being the most common. A total of 45 virulence genes were detected, 22 of which were staphylococcal enterotoxin (SE) genes. Among the identified SE genes, selX exhibited the highest prevalence (86.4%). All isolates carried at least one SE gene. The results of the antimicrobial resistance (AMR) gene detection revealed 41 AMR genes of 12 classes. ß-lactam resistance genes (blal, blaR1, blaZ) and tetracycline resistance gene (tet(38)) exhibited a higher prevalence rate. Core genome single nucleotide polymorphism showed phylogenetic clustering of the isolates with the same region, year, and ST. The results indicated that the SFP isolates in southwest of China harbored multiple toxin and resistance genes, with a high prevalence of new SEs. Therefore, it is important to monitor the antimicrobial susceptibility and SE of S. aureus to reduce the potential risks to public health.

Monocytes to lymphocytes multiplying platelets ratio as an early indicator of acute kidney injury in cardiac surgery with cardiopulmonary bypass: a retrospective analysis.

OBJECTIVE: The monocyte-to-lymphocyte multiplying platelets ratio (MLPR) is a novel systemic inflammatory marker, deriving from the monocyte-to-lymphocyte ratio (MLR). However, the link between MLPR and acute kidney injury following cardiac surgery (CSA-AKI) with cardiopulmonary bypass (CPB) has not been investigated yet. We comprehensively explored the potential linear and nonlinear relationship between MLPR or MLR and CSA-AKI. METHODS: Data of patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected at Fuwai Hospital, Beijing, China. MLPR was defined as monocyte count (×109/L) × 1000/(lymphocyte count (×109/L) × platelets (×109/L)). MLR was defined as monocyte count (×109/L)/lymphocyte count (×109/L). Logistic regression and restricted cubic spline (RCS) were used for linear and nonlinear analysis. The primary outcome was postoperative AKI within 48 h of after cardiac surgery. RESULTS: Of the 2420 patients screened, 2387 eligible patients were enrolled in the final analysis; the mean age was 54.7 years, and 1501 [62.9%] were men. The incidence of AKI was 25.8%. Logistic regression showed that MLPR (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 1.16-1.48, p < .001) and MLR (OR = 3.06, 95% CI: 1.29-7.29, p = .012) were independent risk factors for AKI. Moreover, in the RCS model with adjustment for age (median: 56), female sex, and history of diabetes, a significant statistical difference was detected between preoperative MLPR, MLR, and AKI (p for non-linearity <.001). The subgroup analyses revealed similar results. CONCLUSIONS: The study revealed a nonlinear relationship between MLPR and MLR with AKI. MLPR exhibited a J-shaped curve, and MLR showed a favorable S-shaped curve in relation to AKI. Particularly, MLPR emerges as a promising clinical composite index for early CSA-AKI prediction. These findings emphasize the significance of MLPR as a valuable tool in clinical practice for timely identification and management of CSA-AKI.

Hybrid feature selection in a machine learning predictive model for perioperative myocardial injury in noncoronary cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Perioperative myocardial injury (PMI) is associated with increased mobility and mortality after noncoronary cardiac surgery. However, limited studies have developed a predictive model for PMI. Therefore, we used hybrid feature selection (FS) methods to establish a predictive model for PMI in noncoronary cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This was a single-center retrospective study conducted at the Fuwai Hospital in China. Patients aged 18-70 years who underwent elective noncoronary surgery with CPB at our institution from December 2018 to April 2021 were enrolled. The primary outcome was PMI, defined as the postoperative cardiac troponin I (cTnI) levels exceeding 220 times of upper reference limit (URL). Statistical analyses were conducted by Python (Python Software Foundation, version 3.9.7 and integrated development environment Jupyter Notebook 1.1.0) and SPSS software version 26.0 (IBM Corp., Armonk, New York, USA). RESULTS: A total of 1130 patients were eventually eligible for this study. The incidence of PMI was 20.3% (229/1130) in the overall patients, 20.6% (163/791) in the training dataset, and 19.5% (66/339) in the testing dataset. The logistic regression model performed the best AUC of 0.6893 (95 CI%: 0.6371-0.7382) by the traditional selection method, and the random forest model performed the best AUC of 0.6937 (95 CI%: 0.6416-0.7423) by the union of Wrapper and Embedded method, and the CatBoost model performed the best AUC of 0.6828 (95 CI%: 0.6304-0.7320) by the union of Embedded and forward logistic regression technique, and the Naïve Bayes model achieved the best AUC with 0.7254 (95 CI%: 0.6746-0.7723) by forwarding logistic regression method. Moreover, the decision tree, KNeighborsClassifier, and support vector machine models performed the worse AUC in all selection forms. Furthermore, the SHapley Additive exPlanations plot showed that prolonged CPB, aortic clamp time, and preoperative low platelets count were strongly related to the PMI risk. CONCLUSIONS: In total, four category feature selection methods were utilized, comprising five individual selection techniques and 15 combined methods. Notably, the combination of logistic regression and embedded methods demonstrated outstanding performance in predicting PMI risk. We also concluded that the machine learning model, including random forest, catboost, and Naive Bayes, were suitable candidates for establishing PMI predictive model. Nevertheless, additional investigation and validation are imperative for substantiating these finding.

Identification and molecular docking of tyrosinase inhibitory peptides from allophycocyanin in Spirulina platensis.

BACKGROUND: Tyrosinase, a copper-containing metalloenzyme with catalytic activity, is widely found in mammals. It is the key rate-limiting enzyme that catalyzes melanin synthesis. For humans, tyrosinase is beneficial to the darkening of eyes and hair. However, excessive deposition of melanin in the skin can lead to dull skin color and lead to pigmentation. Therefore, many skin-whitening compounds have been developed to decrease tyrosinase activity. This study aimed to identify a new tyrosinase inhibitory peptide through enzymatic hydrolysis, in vitro activity verification, molecular docking, and molecular dynamics (MD) simulation. RESULTS: A tripeptide Asp-Glu-Arg (DER) was identified, with a '-CDOCKER_Energy' value of 121.26 Kcal mol-1 . DER has effective tyrosinase inhibitory activity. Research shows that its half maximal inhibitory concentration value is 1.04 ± 0.01 mmol L-1 . In addition, DER binds to tyrosinase residues His85, His244, His259, and Asn260, which are key residues that drive the interaction between the peptide and tyrosinase. Finally, through MD simulation, the conformational changes and structural stability of the complexes were further explored to verify and supplement the results of molecular docking. CONCLUSION: This experiment shows that DER can effectively inhibit tyrosinase activity. His244, His259, His260, and Asn260 are the critical residues that drive the interaction between the peptide and tyrosinase, and hydrogen bonding is an important force. DER from Spirulina has the potential to develop functional products with tyrosinase inhibition. © 2024 Society of Chemical Industry.

Incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases.

ER, PgR and HER-2 status are the cornerstones of choosing systemic therapy for breast cancer, but can change during the disease course. Guidelines recommended the biopsy of the metastatic tumor to reassess receptor status. Bone is the most frequent metastatic site of breast cancer but remained technically difficult to biopsy. Our study aimed to evaluate the incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases. One hundred and fifty-five breast cancer patients were diagnosed with pathology-confirmed bone metastasis at Fudan University Shanghai Cancer Center. Ninety-three patients with receptor status available on both primary tumor and bone metastases were included in our study. ER, PgR and HER-2 status converted from positive to negative in 10.8% (10/93), 28.0% (26/93) and 8.6% (8/93) of the patients, while ER, PgR and HER-2 status converted from negative to positive in 3.2% (3/93), 4.3% (4/93) and 1.1% (1/93) of the patients, respectively. 40.4% (17/42) of the HER2-0 tumors converted to HER2-low, which enabled them to receive the treatment of new antibody-drug conjugates (ADCs). Prior endocrine and anti-HER2 therapy were the independent risk factors for receptor conversion. Loss of HR expression in bone metastases was significantly associated with worse first-line PFS (adjusted hazard ratio = 3.271, P-value = .039) and OS (adjusted hazard ratio = 6.09, P-value = .011). In conclusion, our study confirmed that patients may experience receptor conversion between primary breast cancer and bone metastases, possibly influenced by prior treatments, which significantly influenced prognosis. The rebiopsy of bone metastases in patients with primary HER2-0 tumors may benefit from the new ADC drugs.

HER2-low breast cancer: evolution of HER2 expression from primary tumor to distant metastases.

BACKGROUND: Breast cancer (BC) with low human epidermal growth factor receptor 2 (HER2) expression is attracting much attention due to the breakthrough progress of novel anti-HER2 antibody-drug conjugates. HER2 expression is examined in patients with HER2-low BC and their distant metastases in this study, so as to further clarify the dynamic characteristics of HER2 low status in the process of disease progression. METHODS: Patients diagnosed with HER2 low breast cancer (defined as IHC1+ or IHC2+/ISH-) between 2012 and 2021 were included in this study. We evaluated HER2 expression of primary sites and metastatic sites, compared the impact of different clinicopathological parameters on HER2 status of metastases and compared the overall survival and disease-free survival of patients with different HER2 status in metastases. RESULTS: Ninety-eight patients were included. All HER2 IHC scores were confirmed and the consistent rate with the original pathological report was 81.1%. 27.6% of the patients showed different HER2 status in metastases. The HER2 discordance rate differed among different metastatic sites (p = 0.040). The higher the T stage of the primary BC, the higher the rate of HER2 discordance was observed (p = 0.042). For the specimen type of metastasis, HER2 discordant rate was higher in surgical specimen than biopsy (p = 0.050). No difference of HER2 discordance rate was found between HER2-1+ and HER2-2+ patients. But comparing HER2 IHC score, HER2-2+ patients were less likely to have consistent metastatic HER2 levels than HER2-1+ patients (p = 0.006). No difference in survival outcomes was observed between patients with different HER2 status in metastases. CONCLUSIONS: There is a possibility of HER2 expression alteration in the metastases of HER2-low breast cancer. And the rate of altered HER2 low expression was different among different metastatic sites, different T stages of primary BC and specimen type of metastasis. No prognostic significance was observed.

A clinicopathological study and survival analysis of 99 breast cancers with HER2/CEP17 ratio ≥ 2.0 and an average HER2 copy number < 4.0 per cell in China.

BACKGROUND: Breast cancer patients of American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) Group 2 were all HER2-negative according to the 2018 guideline, not HER2-positive as defined in the 2013 guideline. METHODS: We aims to elucidate the unique clinicopathological features of ASCO/CAP Group 2 patients by comparing with classic HER2-nonamplified cancers, and reveal the efficacy of the former to anti-HER2 therapy. The clinicopathological features, treatment and prognosis information of 99 patients between 2014 and 2018 were collected. HER2 status was re-defined using the updated recommendations. RESULTS: Of the 99 ASCO/CAP Group 2 tumors, 25.5% (25/99) tumors were immunohistochemical (IHC) 0/1+ and 74.7% (74/99) tumors were IHC 2+. According to the updated 2018 guideline, all of them were HER2 negative. When compared to ASCO/CAP Group 5, patients of ASCO/CAP Group 2 displayed higher ratio of histological grade 3 (P = .03), high Ki67 proliferation index (P = .03) and pN3 (more than 9 lymph nodes metastasis, P = .02), and lower estrogen receptor (ER) positivity (P = .04). There was no statistical difference in the survival of patients received anti-HER2 therapy and patients not received anti-HER2 therapy. CONCLUSIONS: Patients of ASCO/CAP Group 2 did not received apparent benefit from anti-HER2 treatment. Although according to the updated guidelines and latest reports, HER2 is negative, but when compared with classic HER2-nonamplified cancers, patients of this group seemed to be more aggressive. We suggest that this group still be regarded as an independent category, in order to accumulate more cases in the future to expand the scope of research.

Prognostic factors for the efficacy of infliximab in patients with luminal fistulizing Crohn's disease.

BACKGROUND: Enteric fistula is one of the penetrating features in Crohn's disease (CD). This study aimed to clarify the prognostic factors for the efficacy of infliximab (IFX) treatment in luminal fistulizing CD patients. METHODS: We retrospectively included 26 cases diagnosed with luminal fistulizing CD hospitalized in our medical center from 2013 to 2021. The primary outcome of our research was defined as death from all causes and undergoing of any relevant abdominal surgery. Kaplan-Meier survival curves were used to describe overall survival. Univariate and multivariate analyses were used to identify prognostic factors. A predictive model was constructed using Cox proportional hazard model. RESULTS: The median follow-up time was 17.5 months (range 6-124 months). The 1- and 2-year surgery-free survival rates were 68.1% and 63.2%, respectively. In the univariate analysis, the efficacy of IFX treatment at 6 months after initiation (P < 0.001, HR 0.23, 95% CI 0.01-0.72) and the existence of complex fistula (P = 0.047, HR 4.11, 95% CI 1.01-16.71) was found significantly related to the overall surgery-free survival, while disease activity at baseline (P = 0.099) also showed predictive potential. The multivariate analysis showed that efficacy at 6 months (P = 0.010) was an independent prognostic factor. The C-index of the model for surgery-free survival was 0.923 (P < 0.001), indicating an acceptable predictive effect. CONCLUSION: Prognostic model including the existence of complex fistula, disease activity at baseline and efficacy of IFX at 6 months may be useful to predict long-term outcome of luminal fistulizing CD patients.

Establishment of a comprehensive diagnostic model for neuromyelitis optica spectrum disorders based on the analysis of laboratory indicators and clinical data.

BACKGROUND: To establish a comprehensive diagnostic model for neuromyelitis optica spectrum disorders (NMOSDs) based on laboratory indicators and clinical data. METHODS: A retrospective method was used to query the medical records of patients with NMOSD from January 2019 to December 2021. At the same time, clinical data of other neurological diseases were also collected for comparison. Clinical data of the NMOSD group and non-NMOSD group were analyzed, and the diagnostic model was established based on these data. In addition, the model was evaluated and verified by the receiver operating curve. RESULTS: A total of 73 patients with NMOSD were included, and the ratio of males to females was 1:3.06. The indicators that showed differences between the NMOSD group and non NMOSD group included neutrophils (P = 0.0438), PT (P = 0.0028), APTT (P < 0.0001), CK (P = 0.002), IBIL (P = 0.0181), DBIL (P < 0.0001), TG (P = 0.0078), TC (P = 0.0117), LDL-C (P = 0.0054), ApoA1 (P = 0.0123), ApoB (P = 0.0217), TPO antibody (P = 0.012), T3 (P = 0.0446), B lymphocyte subsets (P = 0.0437), urine sg (P = 0.0123), urine pH (P = 0.0462), anti-SS-A antibody (P = 0.0036), RO-52 (P = 0.0138), CSF simplex virus antibody I-IGG (P = 0.0103), anti-AQP4 antibody (P < 0.0001), and anti-MOG antibody (P = 0.0036). Logistic regression analysis showed that changes in ocular symptoms, anti-SSA antibody, anti-TPO antibody, B lymphocyte subsets, anti-AQP4 antibody, anti-MOG antibody, TG, LDL, ApoB, and APTT had a significant impact on diagnosis. The AUC of the combined analysis was 0.959. The AUC of the new ROC for AQP4- and MOG- antibody negative NMOSD was 0.862. CONCLUSIONS: A diagnostic model was successfully established, which can play an important role in differential diagnosis of NMOSD.

Elderly Patients with Moderate-To-Severe Ulcerative Colitis Are More Likely to Have Treatment Failure and Adverse Outcome.

BACKGROUND AND AIM: The aim of this study was to compare therapeutic responses and prognosis between elderly and nonelderly ulcerative colitis (UC) patients with moderate-to-severe activity. METHODS: 148 UC patients with moderate-to-severe activity hospitalized between 2000 and 2019 were enrolled consecutively, including 74 patients with the age of diagnosis over 60 years and 74 patients diagnosed less than 60 years. Patients were matched by gender, duration (±15%), disease activity, and admission time (±1 year). They were followed up until the latest medical record or December 2019. The primary outcome was UC-related colectomy or death. RESULTS: 148 patients were followed over median 37.5 months. For steroid use, 76.8% of elderly UC patients were responsive, lower than that in adult group (85.7%). A decreased level of clinical activity index (2.0 [-1.5 to 4.00] vs. 6.0 [3.0-8.0], p < 0.001), reduction of C-reactive protein (23.9 [3.5-65.5] vs. 27.8 [9.7-58.1] mg/L), and erythrocyte sedimentation rate (9.0 [-1.3 to 30.5] vs. 15.5 [3.8-36.5] mm/h) at 4 weeks after steroid induction was less obvious in the elderly. More elderly patients manifested steroid dependence and resistance. 28.4% of elderly UC patients took colectomy, remarkably more than adult patients (12.2%), which also occurred earlier (8.0 [0.5-44.75] vs. 39.5 [12-57.38] months, p = 0.001). Aging (hazard ratio [HR] 2.868, 95% confidence interval [CI]: 1.290-6.375, p = 0.01), male, steroid resistance, and occurrence of complications were independently related to colectomy. The rate of serious infections was significantly higher in the elderly (55.4% vs. 35.1%, p = 0.013), mainly including cytomegalovirus infection, bacterial infection, and extraintestinal infection. Aging (odds ratio [OR] 2.774, 95% CI: 1.355-5.675, p = 0.015), extensive colonic involvement, steroid resistance, and biologics usage were independently associated with a high risk of concomitant infections. CONCLUSION: Elderly patients with moderate-to-severe UC experienced more treatment failure and increased risk of UC-related colectomy, mortality, and severe infections, predicting demand for more strict and individualized management.

Physiochemical and Microbial Analysis of Tibetan Yak Milk Yogurt in Comparison to Locally Available Yogurt.

Yak yogurt, which is rich in microorganisms, is a naturally fermented dairy product prepared with ancient and modern techniques by Chinese herdsmen in the Qinghai-Tibet Plateau. The objective of this research was to assess the impact of Lactobacillus bulgaricus and Streptococcus thermophilus starter cultures on the quality and shelf life of yak yogurt, as well as the genetic stability across multiple generations, in comparison to commercially available plain yogurt and peach oat flavor yogurt. Following that, the samples were evenly divided into four treatment groups denoted as T1 (treatment 1), T2, T3, and T4, with each group employing a distinct source of yogurt formulation. T1 included L. bulgaricus, T2 comprised S. thermophilus, T3 consisted of plain yogurt, and T4 represented peach oat yogurt flavor. The findings indicate that T1 yogurt consistently presents a lower pH and higher acidity compared to the other three yogurt types throughout the entire generation process. Moreover, the fat content in all generations of the four yogurt types exceeds the national standard of 3.1 g/100 g, while the total solid content shows a tendency to stabilize across generations. The protein content varies significantly among each generation, with T1 and T4 yogurt indicating higher levels compared to the T2 and T3 yogurt groups. In terms of overall quality, T1 and T4 yogurt are superior to T2 and T3 yogurt, with T1 yogurt being the highest in quality among all groups. The findings revealed that the inclusion of L. bulgaricus led to enhanced flavor, texture, and genetic stability in yak yogurt. This study will serve as a valuable source of data, support, and methodology for the development and screening of compound starters to be utilized in milk fermentation in future research and applications.