Objective To explore the prognostic value of glycolysis-related genes in colorectal cancer (CRC) patients and formulate a novel glycolysis-related prognostic risk model. Methods Single-cell and bulk transcriptomic data of CRC patients, along with clinical information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Glycolysis scores for each sample were calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Kaplan-Meier survival curves were generated to analyze the relationship between glycolysis scores and overall survival. Novel glycolysis-related subgroups were defined among the cell type with the highest glycolysis scores. Gene enrichment analysis, metabolic activity assessment, and univariate Cox regression were performed to explore the biological functions and prognostic impact of these subgroups. A prognostic risk model was built and validated based on genes significantly affecting the prognosis. Gene Set Enrichment Analysis (GSEA) was conducted to explore differences in biological processes between high- and low-risk groups. Differences in immune microenvironment and drug sensitivity between these groups were assessed using R packages. Potential targeted agents for prognostic risk genes were predicted using the Enrichr database. Results Tumor tissues showed significantly higher glycolysis scores than normal tissues, which was associated with a poor prognosis in CRC patients. The highest glycolysis score was observed in epithelial cells, within which we defined eight novel glycolysis-related cell subpopulations. Specifically, the P4HA1⁺ epithelial cell subpopulation was associated with a poor prognosis. Based on signature genes of this subpopulation, a six-gene prognostic risk model was formulated. GSEA revealed significant biological differences between high- and low-risk groups. Immune microenvironment analysis demonstrated that the high-risk group had increased infiltration of macrophages and tumor-associated fibroblasts, along with evident immune exclusion and suppression, while the low-risk group exhibited higher levels of B cell and T cell infiltration. Drug sensitivity analysis indicated that high-risk patients were more sensitive to Abiraterone, while low-risk patients responded to Cisplatin. Additionally, Valproic acid was predicted as a potential targeted agent. Conclusion High glycolytic activity is associated with a poor prognosis in CRC patients. The novel glycolysis-related prognostic risk model formulated in this study offers significant potential for enhancing the diagnosis and treatment of CRC.
Humans ; Colorectal Neoplasms/pathology* ; Glycolysis/genetics* ; Prognosis ; Transcriptome ; Tumor Microenvironment/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Kaplan-Meier Estimate

Objective:To analyze the effect of dexmedetomidine combined with esketamine anesthesia on non-cardiac surgery for coronary heart disease and the effect on hemodynamics,stress response and postoperative complications of patients.Method:A total of 106 patients with coronary heart disease who were going to undergo laparoscopic abdominal surgery from Oct 2021 to Nov 2022 in our hospital were selected and randomly divided into the control group and the observation group,with 53 cases in each group.All patients underwent conventional surgical treatment.The control group was given dexmedetomidine anesthesia,while the observation group was given dexmedetomidine combined with esketamine anesthesia.The surgical indicators,incidence of postoperative complications,diastolic blood pressure(DBP),systolic blood pressure(SBP),pain visual analog scale(VAS),Ramsay sedation score,and the levels of oxide dismutase(SOD),malondialdehyde(MDA),cortisol(Cor)and blood glucose(GLU)were compared between the two groups.Results:There was no statistically significant difference in the operation time between the two groups(P＞0.05),but the postoperative sufentanil dosage of the observation group was lower than that of the control group,and the number of effective compressions was higher than that of the control group(P＜0.05).At 12 h postoperatively,there was no significant difference between the VAS score and Ramsay sedation score of the two groups(P＞0.05),and the VAS score and Ramsay sedation score in the observation group were better than those in the control group at 4 h and 8 h postoperatively(P＜0.05).The levels of MDA,GLU and Cor in both groups increased and the level of SOD decreased at 4 h postoperatively(P＜0.05),and the level of SOD in the observation group was higher than that of the control group,and the levels of MDA,GLU and Cor were lower than those of the control group(P＜0.05).Before anesthesia,there was no statisti-cally significant difference in hemodynamic indexes between the two groups(P＞0.05).Compared with before anesthesia,there were changes in HR,SBP,DBP,and RR of the two groups at the end of the operation and 24 h after the operation(P＜0.05),and the HR,SBP,DBP,and RR of the observation group were better than those of the control group(P＜0.05).The incidence of postoperative complications in the observation group was lower than that in the control group(P＜0.05).Conclusion:Dexmedetomidine combined with esketamine anesthesia can effectively stabilize the hemodynamics of patients,reduce postoperative stress response,and reduce postoperative complications.

Objective To investigate the case characteristics of immune liver injury induced by camrelizumab,and to provide reference for clinical safety of drug use.Methods According to keywords,the case reports of immune liver injury induced by camrelizumab published from the establishment of the database to August 2023 were retrieved and screened,and the data were extracted and analyzed.Results A total of 12 literatures were selected,involving 12 patients,including 7 males and 5 females.Among them,age 43-76 years old,the average age was(62.92±10.19)years old,and most of them developed immune liver injury within 1 month.The primary diseases were all malignant tumors,and the main dosage of camrelizumab was 200mg intravenously,once every 3 weeks;The main immune liver injury was grade 3.After drug withdrawal and corresponding symptomatic treatment,the symptoms improved in 3 cases(25.00%),recovered in 5 cases(41.67%),and did not recover in 4 cases(33.33%).Conclusion Camrelizumab can cause immune liver injury,which can lead to death in severe cases.Therefore,clinical rational use of camrelizumab should be strengthened,the awareness of immune-related adverse events should be improved and pay attention to the immunological liver injury caused by camrelizumab.

Objective:To evaluate the in vitro cross-neutralization of serum antibodies in human and mice immunized with inactivated SARS-CoV-2 vaccine against Delta and Beta variants. Methods:Human serum samples after a second and a third dose of inactivated SARS-CoV-2 vaccine and mouse serum samples after a two-dose vaccination were collected. The neutralizing antibodies in the samples against SARS-CoV-2 strains of prototype, Delta and Beta variants were detected using micro-neutralization assay in biosafety level Ⅲ laboratory. The seroconversion rates and geometric mean titers (GMTs) of antibodies were calculated.Results:The seroconversion rates of antibodies in human serum samples against different SARS-CoV-2 strains were all above 95%. After two-dose vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 109, 41 and 15, respectively. The GMTs decreased by 2.7 folds and 7.3 folds for the Delta and Beta variants as compared with the prototype strain. After the booster vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 446, 190 and 86, respectively. The GMTs of neutralizing antibodies against Delta and Beta variants decreased by 2.3 folds and 5.2 folds as compared with that against the prototype strain. The seroconversion rates of antibodies against different SARS-CoV-2 strains in mouse serum samples were all 100%. The GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 2 037, 862 and 408, respectively. The GMTs decreased by 2.4 folds and 5.0 folds for the Delta and Beta variants.Conclusions:Inactivated SARS-CoV-2 vaccine could induce a certain level of neutralizing antibodies against Delta and Beta variants in both human and mouse models. Moreover, a third dose of vaccine induced higher levels of neutralizing antibodies against Delta and Beta variants in human. This study provided valuable data for the clinical application and protective evaluation of the inactivated SARS-CoV-2 vaccine.

Talaromyces Marneffei infection is rarely reported in patients with chronic active Epstein-Barr virus (EBV) infection. We reported an old man with chronic fever, pleomorphic rash, cough, EBV viraemia, and secondary hemophagocytic syndrome. Repeated histological biopsy and culture of skin lesions revealed Talaromyces Marneffei. This patient was diagnosed as chronic active EBV infection, and Talaromyces Marneffei infection. After treated with glucocorticoid steroids and anti-fungal therapy, the patient finally recovered. EBV infection is usually seen in immune compromised patients, who are susceptible to opportunistic pathogens rarely as Talaromyces Marneffei in this case.

A middle aged male presented with darkened skin and edema of lower extremities was reported. He was diagnosed as primary adrenocortical insufficiency ( Addison' s disease ) accompanied with hypergonadotropic hypogonadism, hypoparathyroidism, and subclinical hypothyroidism after endocrinological workup. In addition, the patient also had thickened skin, hirsutism, and polyserositis. The diagnosis of POEMS syndrome was confirmed by elevated M protein and VEGF level. The image of CT showed normal adrenals. Besides the autoimmune polyglandular syndrome ( APS), the possibility of POEMS syndrome in an adult patient with multiple endocrine dysfunction should be considered.

Objective: To investigate the type 2 innate lymphoid cells (ILC2s) in eosinophilic nasal polyps, non-eosinophilic nasal polyps and controls, and to compare the characteristics of ILC2s indifferent types of nasal polyp. Methods: Flow cytometric analysis was used to quantify the ILC2s and Th2 cells in tissues from 19 patients with chronic rhinosinusitis with nasal polyp (CRSwNP) and 6 controls. The patients were classified into two groups as eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) based on eosinophil counts under hematoxylin-eosin staining. ILC2 and Th2 cell frenquencies, measured as a percentage of CD45⁺ cells, were compared among ECRSwNP group (n=9), non-ECRSwNP group (n=10) and control group (n=6) using Mann-Whitney U test .The correlation between ILC2, Th2 cell frequencies and eosinophil count in tissues was analyzed using Pearson correlation coefficient. Results: ILC2 frequencies in ECRSwNP group were significantly higher than non-ECRSwNP group and controls ((0.051±0.025) vs (0.011±0.017), (0.051±0.025) vs (0.004±0.004), Z value was -3.185, -3.186, respectively, both P<0.05). There was no significant difference between ILC2 frequencies in non-ECRSwNP and controls ((0.011±0.017) vs (0.004±0.004), Z=-0.712, P=0.492). Th2 cell frequencies in ECRSwNP and non-ECRSwNP group were significantly higher than controls ((0.500±0.437) vs (0.106±0.102), (0.275±0.170) vs (0.106±0.102), Z value was -2.946, -2.278, respectively, both P<0.05). There was no significant difference between Th2 frequencies in non-ECRSwNP group and ECRSwNP group ((0.275±0.170) vs (0.500±0.437), Z=-1.306, P=0.211). ILC2 frequencies significantly correlated with Th2 cell frequencies (r=0.571, P=0.011) and tissue eosinophilia (r=0.579, P=0.009). Th2 cell frequencies significantly correlated with tissue eosinophilia (r=0.844, P=0.001). There was no significant association between ILC2 and allergic status. Conclusion ILC2s are elevated in ECRSwNP, and not influenced by allergic status, suggesting that ILC2s play an important role in ECRSwNP without allergic diseases.

Objective: To evaluate the response of oral melphalan plus high-dose dexamethasone (MDex) for patients with primary light chain amyloidosis (pAL). Methods: Clinical data, hematological and organ responses, and survival of 76 patients with pAL who had received MDex from January 2009 to July 2017 were retrospectively analyzed. Results: Of 76 patients (47 males and 29 females with the median age of 56 [range, 20-74] years old), 19.70% patients were defined as Mayo 2004 stage 3, involvement of more than or two organs was presented in 65 (85.53%) patients. Among 60 response evaluable patients, overall hematological response was 48.33% with complete response of 20.00% and very good partial response of 20.00%, respectively. The median time to the hematological response was 5 (range, 1-15) months. 36.67% patients achieved organ response. After the median follow up of 23(range, 1-113) months for surviving patients, median progression-free survival (PFS) and overall survival (OS) were 34 and 43 months, respectively. In a three months landmark analysis, the median rates of PFS and OS were 46 and 65 months, respectively. The median OS rates of patients with Mayo 2004 stage 3 and non Mayo 2004 stage 3 were 5 and 65 months (P=0.001), respectively. Conclusions MDex was an effective treatment for patients with early stage pAL, but was not suitable for those with severe cardiac involvement.

Objective: To evaluate the clinical characteristics and outcomes of very high risk patients with primary immunoglobulin light-chain amyloidosis (pAL) at a single center in China. Method: Clinical data, treatment and outcome of 205 pAL patients in Peking Union Medical College Hospital from January 2009 to February 2016 were retrospectively analyzed. A 'very high risk’ group includes patients with Mayo 2004 stage Ⅲb and Mayo 2012 stage 4. Results: Of 205 patients, 34 (16.6%) were defined as very high risk pAL patients. The median age at diagnosis was 57 (20-84) years, and 22 patients (64.7%) were male. All 34 patients were diagnosed with cardiac involvement, multi-organ involvement was observed in 15 patients (44.1%) , and 27 (81.8%) had New York Heart Association Class Ⅲ or Ⅳ. Median values of serum cTnI, NT-proBNP, and free light chains difference were 0.25 μg/L, 11 733 ng/L, and 403 mg/L, respectively. Eight (24.2%) had more than 10% plasma cell on the bone marrow aspirate. Sixteen (47.1%) patients received bortezomib based chemotherapy and overall hematologic response rate was 58.3%. Median overall survival (OS) was 4 months. The estimated OS at 3, 6, 12, and 24 months was 51.3%, 44.0%, 35.2%, and 29.6%, respectively. Fourteen (41.2%) patients died within 3 months after the diagnosis. The estimated 1-year survival rate for the patients who got hematologic response, without hematologic response, and palliative treatment was 90.9%, 11.1%, and 0, respectively (P<0.001) . Conclusion Patients with very high risk pAL had very poor prognosis and the early death rate remained high. Those patients who obtained hematologic remission would have significantly better outcomes.

Monoclonal protein (M protein) is a serum surrogate used to conduct diagnostic, prognostic, and therapeutic evaluations of monoclonal plasma cell proliferative disorders. Two basic methods, namely, serum protein electrophoresis and immunofixation elec-trophoresis, are employed to detect and characterize M protein. Although these techniques have considerably improved, M protein quantification exhibits several drawbacks. In serum protein electrophoresis, M protein can migrate to various locations, and low M pro-tein levels cannot form a typical peak;as a consequence, additional problems in measurements arise. In 2009, a novel immunoassay in-volving a heavy/light chain (HLC) was developed. HLC recognizes immunoglobulins with specific heavy and light chain isotypes. The ra-tio between an involved monoclonal immunoglobulin and an uninvolved background polyclonal immunoglobulin can be calculated through immunoglobulin quantitation by using isotype-specific light chains. This review summarizes relevant parameters that provide diagnostic, prognostic, and therapeutic data regarding monoclonal plasma cell proliferative disorders.