How group structure impacts the numbers at risk for coronary artery disease: polygenic risk scores and non-genetic risk factors in the UK Biobank cohort.

The UK Biobank is a large cohort study that recruited over 500,000 British participants aged 40-69 in 2006-2010 at 22 assessment centres from across the UK. Self-reported health outcomes and hospital admission data are two types of records that include participants' disease status. Coronary artery disease (CAD) is the most common cause of death in the UK Biobank cohort. After distinguishing between prevalence and incidence CAD events for all UK Biobank participants, we identified geographical variations in age-standardised rates of CAD between assessment centres. Significant distributional differences were found between the pooled cohort equation scores of UK Biobank participants from England and Scotland using the Mann-Whitney test. Polygenic risk scores of UK Biobank participants from England and Scotland and from different assessment centres differed significantly using permutation tests. Our aim was to discriminate between assessment centres with different disease rates by collecting data on disease-related risk factors. However, relying solely on individual-level predictions and averaging them to obtain group-level predictions proved ineffective, particularly due to the presence of correlated covariates resulting from participation bias. By using the Mundlak model, which estimates a random effects regression by including the group means of the independent variables in the model, we effectively addressed these issues. In addition, we designed a simulation experiment to demonstrate the functionality of the Mundlak model. Our findings have applications in public health funding and strategy, as our approach can be used to predict case rates in the future, as both population structure and lifestyle changes are uncertain.

Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma.

BACKGROUND: The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. METHODS: We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). RESULTS: Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell-cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. CONCLUSIONS: This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

Regiodivergent Hydrosilylation of Polar Enynes to Synthesize Site-Specific Silyl-Substituted Dienes.

Herein, we present catalyst-regulated switchable site-selective hydrosilylation of enynes, which are suitable for a wide range of alkyl and aryl substituted polar enynes and exhibit excellent functional group compatibility. Under the optimized conditions, silyl groups can be precisely installed at various positions of 1,3-dienes. While α- and γ-silylation products were obtained under platinum-catalytic systems, ß-silylation products were delivered with [Cp*RuCl]4 as catalyst. This process lead to the formation of 1,3-dienoates with diverse substitutions, which would pose challenges with other methodologies.

Outcomes following the excision of sarcoma and chest wall reconstruction using 3D printed implant.

The survival outcomes of patients with chest wall sarcomas (CWS) were evaluated after receiving wide excision and chest wall reconstruction by using three-dimensional printed (3DP) implants. The survival outcomes evaluating the effect of 3DP implants for chest wall reconstruction is lacking. Here, forty-nine patients with CWS underwent radical wide excision and chest wall reconstruction using 3DP implants. The surgical data and long-term survival outcomes were collected and analyzed. With a median follow-up of 36 months, the disease-free survival (DFS) and overall survival (OS) were 31.7% and 58.5%, respectively. In addition, the 3-year DFS and OS can be significantly differentiated using the classification criteria of tumor grade, tumor size tumor area. Hence, wide excision and chest wall reconstruction using three-dimensional printed implants are a safe and effective treatment for chest wall sarcoma. The novel classification criteria of tumor size and area have the potential to predict the prognosis of CWS.

Early postoperative endoscopy for predicting anastomotic leakage after minimally invasive esophagectomy: A large-volume retrospective study.

BACKGROUND: Anastomotic leakage is one of the most severe adverse events of minimally invasive esophagectomy for esophageal cancer. Early postoperative endoscopy is considered to be the most objective means to diagnose anastomotic leakage, but its safety is questioned by clinicians. This study aimed to evaluate the safety and effectiveness of early postoperative endoscopy in predicting anastomotic leakage. METHODS: Patients who underwent minimally invasive esophagectomy (from January 2017 to June 2021) in our center were identified and divided into early postoperative endoscopy and control groups according to whether they underwent early postoperative endoscopy within 72 hours after surgery. Propensity score matching was used to balance baseline characteristics. The incidence of postoperative adverse events was compared between the 2 groups, risk variables for anastomotic leakage were identified using logistic regression, and abnormal endoscopic findings related to anastomotic leakage occurrence were explored. RESULTS: A total of 436 patients were enrolled, of whom 134 underwent early postoperative endoscopy. One hundred and thirty-two pairs were matched by propensity score matching, and baseline characteristics were well-balanced. Both before and after propensity score matching, early postoperative endoscopy did not increase the incidence of postoperative adverse events (chyle leak, hypoproteinemia, pneumonia, etc) and in-hospital mortality. Notably, the incidence of anastomotic leakage (9.8% vs 22.7%) and the length of mean postoperative hospital stay (17.6 vs 20.9 days) was significantly decreased in the early postoperative endoscopy group. Finally, based on the findings under early postoperative endoscopy, we found that gastric graft ischemia is related to a higher incidence of anastomotic leakage (P = .023). CONCLUSION: Early postoperative endoscopy does not increase postoperative adverse events after minimally invasive esophagectomy and may guide early prediction and intervention strategies for anastomotic leakage in patients undergoing minimally invasive esophagectomy.

Anchoring Charge Selective Self-Assembled Monolayers for Tin-Lead Perovskite Solar Cells.

Self-assembled monolayers (SAMs) have displayed great potential for improving efficiency and stability in p-i-n perovskite solar cells (PSCs). The anchoring of SAMs at the conductiv metal oxide substrates and their interaction with perovskite materials must be rationally tailored to ensure efficient charge carrier extraction and improved quality of the perovskite films. Herein, SAMs molecules with different anchoring groups and spacers to control the interaction with perovskite in the p-i-n mixed Sn-Pb PSCs are selected. It is found that the monolayer with the carboxylate group exhibits appropriate interaction and has a more favorable orientation and arrangement than that of the phosphate group. This results in reduced nonradiative recombination and enhanced crystallinity. In addition, the short chain length leads to an improved energy level alignment of SAMs with perovskite, improving hole extraction. As a result, the narrow bandgap (≈1.25 eV) Sn-Pb PSCs show efficiencies of up to 23.1% with an open-circuit voltage of up to 0.89 V. Unencapsulated devices retain 93% of their initial efficiency after storage in N2 atmosphere for over 2500 h. Overall, this work highlights the underexplored potential of SAMs for perovskite photovoltaics and provides essential findings on the influence of their structural modification.

A gene-based score for the risk stratification of stage IA lung adenocarcinoma.

OBJECTIVE: We aim to molecularly stratify stage IA lung adenocarcinoma (LUAD) for precision medicine. METHODS: Twelve multi-institution datasets (837 cases of IA) were used to classify the high- and low-risk types (based on survival status within 5 years), and the biological differences were compared. Then, a gene-based classifying score (IA score) was trained, tested and validated by several machine learning methods. Furthermore, we estimated the significance of the IA score in the prognostic assessment, chemotherapy prediction and risk stratification of stage IA LUAD. We also developed an R package for the clinical application. The SEER database (15708 IA samples) and TCGA Pan-Cancer (1881 stage I samples) database were used to verify clinical significance. RESULTS: Compared with the low-risk group, the high-risk group of stage IA LUAD has obvious enrichment of the malignant pathway and more driver mutations and copy number variations. The effect of the IA score on the classification of high- and low-risk stage IA LUAD was much better than that of classical clinicopathological factors (training set: AUC = 0.9, validation set: AUC = 0.7). The IA score can significantly predict the prognosis of stage IA LUAD and has a prognostic effect for stage I pancancer. The IA score can effectively predict chemotherapy sensitivity and occult metastasis or invasion in stage IA LUAD. The R package IAExpSuv has a good risk probability prediction effect for both groups and single stages of IA LUAD. CONCLUSIONS: The IA score can effectively stratify the risk of stage IA LUAD, offering good assistance in precision medicine.

Apoptotic bodies inhibit inflammation by PDL1-PD1-mediated macrophage metabolic reprogramming.

Apoptosis triggers immunoregulation to prevent and suppress inflammation and autoimmunity. However, the mechanism by which apoptotic cells modulate immune responses remains largely elusive. In the context of allogeneic mesenchymal stem cells (MSCs) transplantation, long-term immunoregulation is observed in the host despite the short survive of the injected MSCs. In this study, utilizing a mouse model of acute lung injury (ALI), we demonstrate that apoptotic bodies (ABs) released by transplanted human umbilical cord MSCs (UC-MSCs) convert the macrophages from a pro-inflammatory to an anti-inflammatory state, thereby ameliorating the disease. Mechanistically, we identify the expression of programmed cell death 1 ligand 1 (PDL1) on the membrane of UC-MSCs-derived ABs, which interacts with programmed cell death protein 1 (PD1) on host macrophages. This interaction leads to the reprogramming of macrophage metabolism, shifting from glycolysis to mitochondrial oxidative phosphorylation via the Erk-dependent pathway in ALI. Importantly, we have reproduced the PDL1-PD1 effects of ABs on metabolic switch using alveolar macrophages from patients with ALI, suggesting the potential clinical implications of developing therapeutic strategies for the patients.

Biotoxicity of Halide Perovskites in Mice.

Halide perovskites are crystalline semiconductors with exceptional optoelectronic properties, rapidly developing toward large-scale applications. Lead (II) (Pb2+ ) is the core element used to prepare halide perovskites. Pb2+ can displace key 2+ elements, including calcium, zinc and iron, that regulate vital physiological functions. Sn2+ can replace Pb2+ within the perovskite structure and, if accidentally dispersed in the environment, it readily oxidizes to Sn4+ , which is compatible with physiological functions and thus potentially safe. The 3+ salt bismuth (III) (Bi3+ ) is also potentially safe for the same reason and useful to prepare double perovskites. Here, this work studies the biotoxicity of Pb, Sn, and Bi perovskites in mice for the first time. This work analyses histopathology and growth of mice directly exposed to perovskites and investigate the development of their offspring generation. This study provides the screening of organs and key physiological functions targeted by perovskite exposure to design specific studies in mammalians.

Electrochemical Phenyl-Carbonyl Coupling Reaction of Aromatic Aldehydes or Ketones.

An electrochemical phenyl-carbonyl coupling reaction of aromatic aldehydes or ketones to synthesize 4-(hydroxy(phenyl)methyl)benzaldehyde derivatives has been developed. The method shows high chemoselectivity, broad functional group compatibility, atom economy, and environmental benignity and has good potential applicability.

Effects of zero-valent iron (ZVI) on nitrogen conversion, transformation of sulfamethoxazole (SMX) and abundance of antibiotic resistance genes (ARGs) in aerobic granular sludge process.

Even after pre-treatment, livestock and poultry wastewater still contain high concentrations of ammonia and residual antibiotics. These could be removed economically using the aerobic granular sludge (AGS) process with zero-valent iron (ZVI). The interaction of antibiotics and nitrogen in this process needs to be clarified and controlled, however, to achieve good removal performance. Otherwise, antibiotics might generate transformation products (TPs) with higher toxicity and lead to the emergence of antibiotic-resistant bacteria carrying antibiotic resistance genes (ARGs), which could cause persistent toxicity and the risk of disease transmission to the ecological environment. This study investigated the impact of ZVI on AGS for nitrogen and sulfamethoxazole (SMX) removal. The results show that AGS could maintain good ammonia removal performance and that the existence of SMX had a negative impact on ammonia oxidation activities. ZVI contributed to an increase in the abundance of nitrite oxidation bacteria, denitrifying bacteria and the functional genes of nitrogen removal. This led to better total nitrogen removal and a decrease in N2O emission. Accompanied by biological nitrogen transformation, SMX could be transformed into 14 TPs through five pathways. ZVI has the potential to enhance transformation pathways with TPs of lower ecotoxicity, thereby reducing the acute and chronic toxicity of the effluent. Unfortunately, ZVI might enhance the abundance of sul1, sul2, and sul3 in AGS, which increases the risk of sulfonamide antibiotic resistance. In AGS, Opitutaceae, Xanthomonas, Spartobacteria and Mesorhizobium were potential hosts for ARGs. This study provides theoretical references for the interaction of typical antibiotics and nitrogen in the biological treatment process of wastewater and bioremediation of natural water bodies.

Synthesis and Transformation of Bis(silyl)-Substituted Conjugated Vinylallene Compounds.

We develop a copper-catalyzed disilylation of polysubstituted pent-1-en-4-yn-3-yl acetate derivatives, which in one pot furnishes the bis(silyl)-substituted vinylallenes in moderate yields under mild reaction conditions. The reaction shows broad substrate scope and single stereoselectivity. Besides, we develop a method to decrease the electrocyclization temperature of vinylallenes for the synthesis of methylenecyclobutenes by installing bis(silyl) substituents. And the effect of a silyl substituent on electrocyclization of vinylallenes was studied via DFT computation. The synthetic method features broad substrate scope and excellent stereoselectivity.

Predictive Value of COPD History on In-Stent Restenosis in Coronary Arteries Following Percutaneous Coronary Intervention.

Objective: Chronic obstructive pulmonary disease (COPD) is a prevalent chronic respiratory disease that poses a significant health risk to individuals. Patients with COPD are predisposed to a higher incidence of coronary artery disease (CAD) than the general population. This study aims to investigate the correlation between COPD and the incidence of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). Methods: This study retrospectively analyzed the clinical data and laboratory test results of patients who underwent PCI at our hospital between January 2018 and December 2021 to investigate the relationship between COPD and drug-Eluting Stents (DES) postoperative ISR. We employed the best subset method to select the most suitable combination of predictive factors, utilizing the data, and verified the precision of the model by means of internal validation. We ultimately assessed the performance of the prediction model using an ROC curve. Results: The research indicates that COPD is an independent risk factor for ISR after PCI (OR=2.437, 95% CI [1.336, 4.495], P=0.004). The analysis revealed an area under the receiver operating characteristic (ROC) curve of 0.783 for the training group and 0.705 for the testing group, indicating a model fitting for both groups (both > 0.5). Conclusion: COPD history is a dependable predictor of stent restenosis post percutaneous coronary intervention.

Circulating tumor DNA minimal residual disease in clinical practice of non-small cell lung cancer.

INTRODUCTION: The advance of diagnostics and treatments has greatly improved the prognosis of non-small cell lung cancer (NSCLC) patients. However, relapse and metastasis are still common problems encountered by NSCLC patients who have achieved complete remission. Therefore, overcoming the challenge of relapse and metastasis is particularly important for improving the prognosis of NSCLC patients. Research has shown that minimal residual disease (MRD) was a potential source of tumor relapse and metastasis, and circulating tumor DNA (ctDNA) MRD has obvious advantages in predicting the relapse and metastasis of NSCLC and evaluating treatment effectiveness. Therefore, dynamic monitoring of MRD is of great significance for NSCLC patient management strategies. AREAS COVERED: We have reviewed articles related to NSCLC MRD included in PubMed and describes the biological significance and historical context of MRD research, reasons for using ctDNA to evaluate MRD, and potential value and challenges of ctDNA MRD in assessing relapse and metastasis of NSCLC, ultimately guiding clinical therapeutic strategies and management. EXPERT OPINION: The standardized scope of ctDNA MRD detection for NSCLC requires more clinical research evidence to minimize study differences, making it possible to include in the clinical staging as a reliable indicator.

Simulation study of an x-ray sub-picosecond resolution detection system based on time-domain amplification.

This study proposes what we believe to be a novel x-ray detection system that achieves a temporal resolution of 930 fs with photorefractive and four-wave mixing effects. The system comprises two parts: a signal-conversion system and signal-acquisition system. The signal-conversion system is based on the photorefractive effect, which converts x-ray evolution into the variation of infrared interference intensity. The signal-conversion sensor consists of ultra-fast response LT-GaAs and a high-resolution interference cavity, achieving a resolution of  767 fs. The signal-acquisition system consists of a time-domain amplification system based on four-wave mixing and a high-resolution signal-recording system with a resolution of 21 ps, providing a temporal resolution of 525 fs.

Next-generation sequencing-based detection in a breast MMPMN patient with EGFR T790M mutation: a rare case report and literature review.

Multiple primary malignant neoplasms (MPMNs) are difficult to identify from the metastasis or recurrence of malignant tumors. Additionally, the genetic mutations in each primary tumor vary from each other; therefore, it is critical to explore potential abnormal genes. Next-generation sequencing (NGS) technology has emerged as a reliable approach for detecting mutated genes in primary tumors and can provide several targeted therapeutic options for patients with MPMNs. Here, we report a case of metachronous multiple primary malignant neoplasm (MMPMN) patient with primary ovarian and breast cancer. Targeted NGS genetic profiling revealed a rare EGFR T790M mutation in this patient's primary breast tumor tissue, which has only been reported previously in breast cancer (BC). Based on the NGS results, osimertinib was recommended for this patient. Although this patient did not receive osimertinib because of gastrointestinal hemorrhage, this case highlights the significance of NGS technology in the diagnosis and treatment of MPMNs.

Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non-Small Cell Lung Cancer: The TD-FOREKNOW Randomized Clinical Trial.

Importance: The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown. Objective: To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC. Design, Setting, and Participants: In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022. Interventions: Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks. Main Outcomes and Measures: The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis. Results: Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported. Conclusions and Relevance: This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04338620.

Regio- and enantioselective CuH-catalyzed 1,2- and 1,4-hydrosilylation of 1,3-enynes.

We report a copper-catalyzed ligand-controlled selective 1,2- and 1,4-hydrosilylation of 1,3-enynes, which furnishes enantiomerically enriched propargyl- and 1,2-allenylsilane products in high yields with excellent enantioselectivities (up to 99% ee). This reaction proceeds under mild conditions, shows broad substrate scope for both 1,3-enynes and trihydrosilanes, and displays excellent regioselectivities. Mechanistic studies based on deuterium-labeling reactions and density functional theory (DFT) calculations suggest that allenylcopper is the dominant reactive intermediate under both 1,2- and 1,4-hydrosilylation conditions, and it undergoes metathesis with silanes via selective four-membered or six-membered transition state, depending on the nature of the ligand. The weak interactions between the ligands and the reacting partners are found to be the key controlling factor for the observed regioselectivity switch. The origin of high enantiocontrol in the 1,4-hydrosilylation is also revealed by high level DLPNO-CCSD(T) calculations.

Secondary thrombocythemia with ST-segment elevation myocardial infarction as the first manifestation: a case report.

Secondary thrombocythemia (ST), also called reactive thrombocytosis, is caused by a disorder that triggers increased production by normal platelet-forming cells and is characterized by the abnormally increased number of platelet and megakaryocytes in the bone marrow. Previous reports have found complications from malignant tumors, chronic inflammation, acute inflammation, acute hemorrhage, splenectomy, etc. to be the common causes of ST. However, reports of secondary thrombocytosis caused by antibiotics are limited and there are no reports of secondary thrombocytosis with acute myocardial infarction as the first presentation. If the patient is at high risk of thrombosis, intensive antithrombotic therapy is required. To raise clinicians' awareness of drug-induced secondary thrombocytosis and to enhance antithrombotic therapy for high-risk patients, this article presented a case of drug-induced secondary thrombocytosis with acute ST-segment elevation myocardial infarction as the primary manifestation. Case presentation: An 80-year-old woman was admitted with cardiogenic shock due to post-activity chest pain. She was started on aspirin and clopidogrel antiplatelet therapy, then replaced aspirin with indolibuprofen, which has relatively few side effects. There was no significant decrease in platelet counts during treatment. Clinical discussion: Secondary thrombocythemia, characterized by nonspecific symptoms, is difficult to diagnose. Secondary thrombocytosis with acute myocardial infarction as the first symptom is uncommon, but is very urgent and associated with a poor prognosis. What's more, cause-specific treatment counts for secondary thrombocythemia. Therefore it is important to search for the causal factor of secondary thrombocytosis. Secondary thrombocytosis caused by cephalosporins is rare. There is a need to arouse the attention of clinicians to the ST caused by cephalosporins and to provide a guide of treatment to these patients. Conclusion: After a thorough analysis of the pertinent literature, we discovered that several retrospective studies demonstrated the effectiveness of cytoreductive therapy in significantly reducing platelet counts. Based on this finding, we prescribed hydroxyurea to our patient, which led to a gradual decrease in platelet count and ultimately resulted in a return to normal levels.

Polymorphism, Genetic Effect, and Association with Egg-Laying Performance of Chahua Chickens Matrix Metalloproteinases 13 Promoter.

Matrix metalloproteinases are a group of proteases involved in the regulation of ovarian follicular development and ovulation. Among the different MMPs, MMP13 is known to play an important role in reproduction. Therefore, this study aimed to screen the molecular genetic markers of the MMP13 gene that affect the egg-laying performance of Chahua chickens. Polymerase chain reaction (PCR) and sequencing were performed in the 5' regulation region of the MMP13 gene to detect loci significantly related to the egg-laying performance of Chahua chickens. A double fluorescence reporting system, quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to study whether gene expression was regulated by identified sites, providing a theoretical basis to improve egg production in Chahua chickens. The results revealed six single nucleotide polymorphisms (SNPs; A-1887T, T-1889C, A-1890T, T-2252C, T-2329C, and C-2360A) in the promoter region of the MMP13 gene. Further analysis revealed that hens with T-1890-C-1889-T-1887/T-1890-C-1889-T-1887 (mutant type, MT) had an earlier age at first egg (AFE) than hens with A-1890-T-1889-A-1887/A-1890-T-1889-A-1887 (wild type, WT; p < 0.05). RT-qPCR showed that the relative expression level of the MMP13 gene in the ovarian tissues of individuals with the mutation was higher than that of individuals with the wild gene (p < 0.05). Western blot results confirmed higher levels of the MMP13 protein in MT ovaries compared to those in WT ovaries. Thus, this study suggests that mutation sites on the MMP13 promoter may affect gene expression. In conclusion, the MMP13 gene in Chahua chickens may be significant for egg-laying performance, and the polymorphism in its promoter region could be used as a molecular marker to improve egg-laying performance.