OBJECTIVE To investigate the metabolic changes in MEG-01 megakaryocytes after treatment with linezolid （LZD） from metabolomic perspective and its impact on the the proliferation of cells and generation of platelet precursors. METHODS MEG-01 cells were seeded in proliferation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 100， 200， 400， 800 μg/mL LZD groups. The proliferation status of cells in each group was observed under the microscope； cell proliferation and viability were assessed. Cells were also seeded in differentiation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 400 μg/mL LZD group； after 14 days of culture， platelet precursor generation was observed under the microscope； immunofluorescence staining was performed to count the proportion of cells producing pseudopodia， the relative length of pseudopodia was measured， and the expression levels of CD41 and CD42b mRNA were assessed. Cells from the solvent control group and the 400 μg/mL LZD group， cultured in differentiation medium for 14 days， were extracted and subjected to non-targeted metabolomics and targeted energy metabolomics analysis using liquid chromatography-tandem mass spectrometry. The relative content of pyruvate in cells， after being cultured for 14 days with the addition of pyruvate （10 mmol/L） or LZD （400 μg/mL）+pyruvate （10 mmol/L）， was measured and observed， as well as its effects on cell proliferation and platelet precursor generation. RESULTS 400 μg/mL LZD could significantly inhibit the proliferation of MEG-01 cells and the generation of platelet precursors （P＜0.01）. Non-targeted metabolomic analysis of MEG-01 cells after 400 μg/mL LZD treatment revealed significant changes in energy metabolism-related pathways such as mTOR signaling pathway， alanine， aspartate and glutamate metabolism， and central carbon metabolism in cancer. Targeted energy metabolomic analysis further showed that the relative contents of adenosine triphosphate， guanosine triphosphate， and pyruvate in MEG-01 cells were significantly reduced （P＜0.01）， while the relative contents of lactate were significantly increased （P＜0.01）. Compared with the LZD group， the relative content of pyruvate， cell count， the proportion of cells producing pseudopodia and the relative length of pseudopodia were significantly increased in the LZD+pyruvate group （P＜0.01）. CONCLUSIONS LZD may reduce pyruvate production by inhibiting mitochondrial energy metabolism， thereby suppressing megakaryocyte proliferation and platelet precursor production， ultimately leading to the occurrence of thrombocytopenia.

Objective To investigate the clinical diagnostic value of plasma serine protease inhibitor Ka-zal-type 4(SPINK4)expression in colorectal adenocarcinoma(CRC)and progressive adenoma(AA).Methods A total of 62 patients with CRC(CRC group)and 15 patients with AA(AA group)diagnosed by colonoscopy and pathological examination in this hospital from June 2020 to December 2021 were selected,and 22 healthy people undergoing physical examination during the same period were selected as the HC group.The expression of SPINK4 in plasma was detected by ELISA,and the expression of CEA in plasma was detected by electrochemiluminescence,and the correlation was analyzed.The diagnostic efficiency was analyzed by re-ceiver operating characteristic(ROC)curve,and the expression of p53 in CRC tissues was detected by immu-nohistochemistry.Results The expression of plasma SPINK4 in the CRC group and AA group was lower than that in the HC group(Z=3.72,-0.41,P＜0.05),and the expression of CEA in the CRC group was higher than that in the HC group(Z=-3.63,P＜0.05).The area under the curve(AUC),accuracy,sensi-tivity and specificity of SPINK4 combined with CEA in the diagnosis of CRC and AA were higher than those of SPINK4 and CEA alone.The positive rate of mutant type p53 in SPINK4 low expression group and CEA high ex-pression group was significantly increased in CRC patients(72.55％,75.00％,P＜0.05).Conclusion The expression of plasma SPINK4 is decreased in CRC and AA,and the combined detection of SPINK4 and CEA has a good di-agnostic efficiency in CRC and AA.

The characteristic features of dissociative conversion disorder entail a partial or complete loss of normal integration in memory,identity awareness,immediate sensation,and motor control.This article documents a case of the disorder presenting with an onset of depressive mood,diminished interest,and facial tics,subsequently accompanied by intermittent fainting spells with limb convulsions.Despite multiple consultations in both general hospitals and psychiatric settings,and despite treatment with various antidepressants and antiepileptic medications,the patient's symptoms showed no significant improvement.The report of this case deepens the understanding of a complex and commonly misdiagnosed condition,offering valuable insights for the diagnosis and treatment of patients exhibiting similar symptoms.

With the increasing incidence of esophagogastric junction carcinoma, the application rate of proximal gastrectomy has been rising annually. There is a wide variety of methods for digestive tract reconstruction after proximal gastrectomy, and some of these reconstruction methods have been introduced relatively recently, with limited clinical experience, which led to a lack of standardization. Such a situation will inevitably result in inconsistent clinical outcomes of proximal gastrectomy with digestive tract reconstruction. To promote the standardization of digestive tract reconstruction after proximal gastrectomy, improve the clinical efficacy of proximal gastrectomy, and reduce the occurrence of postoperative complications, this article elaborates on the indications, surgical steps and technical points of the four methods after proximal gastrectomy recommended by the "Chinese consensus on digestive tract reconstruction after proximal gastrectomy (2020 edition)", such as double tract, side overlap, double flaps and gastric tube reconstruction, providing guidance for the application of digestive tract reconstruction after proximal gastrectomy.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

With the increasing incidence of esophagogastric junction carcinoma, the application rate of proximal gastrectomy has been rising annually. There is a wide variety of methods for digestive tract reconstruction after proximal gastrectomy, and some of these reconstruction methods have been introduced relatively recently, with limited clinical experience, which led to a lack of standardization. Such a situation will inevitably result in inconsistent clinical outcomes of proximal gastrectomy with digestive tract reconstruction. To promote the standardization of digestive tract reconstruction after proximal gastrectomy, improve the clinical efficacy of proximal gastrectomy, and reduce the occurrence of postoperative complications, this article elaborates on the indications, surgical steps and technical points of the four methods after proximal gastrectomy recommended by the "Chinese consensus on digestive tract reconstruction after proximal gastrectomy (2020 edition)", such as double tract, side overlap, double flaps and gastric tube reconstruction, providing guidance for the application of digestive tract reconstruction after proximal gastrectomy.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Objective To retrospectively analyze the diagnostic value of thrombin-antithrombin complex(TAT),thrombomodulin(TM),and tissue plasminogen activator-inhibitor complex(t-PAIC)in severe cases of corona virus disease 2019(COVID-19).Methods A cohort of 79 patients clinically diagnosed with COVID-19 was retrospectively assembled and categorized into two groups based on disease severity:non-severe(n=51)and severe(n=28).In this study the differences of coagulation function and inflamma-tory marker levels between the two groups were compared.The correlations of TAT,TM and t-PAIC with other biomarkers were investi-gated.The diagnostic values of all the markers for severe COVID-19 were assessed.Results The patients of severe COVID-19 exhibi-ted significantly higher levels of TAT,TM,and t-PAIC compared to those of non-severe group(P＜0.001).The levels of TAT,TM and t-PAIC showed notable positive correlation with other biomarkers.TAT demonstrated the strongest positive correlation with the level of D-dimer(r=0.786,P＜0.001).Binary logistic regression analysis identified TAT(OR=1.346,P＜0.05)and t-PAIC(OR=1.128,P＜0.05)were independent risk factors in term of severe COVID-19.The combined ROC curve for TAT,TM and t-PAIC revealed high diagnostic efficacy in severe cases with the area under the curve(AUCROC)were 0.918,and the sensitivity and specificity were of 75％and 94.1％,respectively.Conclusion The results of combined measurement of TAT,TM and t-PAIC effectively demonstrates its diagnostic value in identifying severity and stratification of COVID-19 cases and may have important clinical significance for assessment of the severity and prediction of the prognosis.

Fracture is a disease caused by violence or bone disease in which the continuity of bone structure is completely or partially broken. The healing of fracture mainly includes three processes: hematoma mechanization stage, callus formation stage and callus remodeling stage. At different stages, various cells and molecules are important factors regulating fracture healing. There is growing evidence that miRNA plays an important role in various bone diseases, such as osteosarcoma, osteoarthritis, osteonecrosis, and fractures. Recent studies have shown that miRNA can regulate the process of fracture healing and may be potential biomarkers of fracture healing. This article reviews the expression, function and mechanism of miRNA in the process of fracture healing.

Microcephaly is a common pediatric neurodevelopmental disorder with complex etiology. In recent years, with the development of brain organoid technology, there has been rapid progress in understanding the pathogenesis and treatment strategies of microcephaly using this technology. This article elucidates the advantages of brain organoids over traditional experimental models, reviews the research progress of brain organoid technology in disease modeling and drug screening for various causes of microcephaly, and discusses the limitations and future prospects of brain organoids.