OBJECTIVE To evaluate the efficacy and safety of letermovir in preventing cytomegalovirus （CMV） infection after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. METHODS A retrospective cohort study was conducted， enrolling patients who underwent allo-HSCT at the Department of Hematology， Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine， from August 30， 2022， to February 21， 2024. Patients who initiated letermovir prophylaxis within 28 days post-transplantation were assigned to the experimental group （99 cases）， while those who did not initiate letermovir within this period were assigned to the control group （18 cases）. The incidence and clinical characteristics of CMV infection （including the number of wangranran@xinhuamed.com.cn CMV infection cases， the number of cases progressing to CMV disease， recurrent CMV disease， onset time of CMV infection， and treatment duration）， immune function recovery within 120 days post-transplantation， and the occurrence of transplantation-related complications （including CD4+ and CD8+ T-cell recovery， Epstein-Barr virus infection， acute graft-versus-host disease， human herpesvirus 6 infection， and posttransplant lymphoproliferative disorders） and adverse events were recorded. Univariate and multivariate Cox regression analyses were performed to identify factors influencing CMV infection. RESULTS A total of 117 patients were included， among whom 15 developed CMV infection， 5 progressed to CMV disease， and 2 experienced recurrent CMV disease. The CMV infection rate in the experimental group was significantly lower than that in the control group （P＜0.001）， and the onset time of CMV infection was significantly delayed （P＝0.014）. The proportion of patients with CD4+ T-cell counts ≥200 cells/μL in the experimental group was significantly lower than that in the control group （P＝0.022）. During the follow-up period， elevated creatinine levels were observed in 1 patient， and nausea and vomiting were observed in 2 patients. Multivariate Cox regression analysis revealed that the use of high-dose corticosteroids was a risk factor for CMV infection （HR＝6.230， 95%CI of 1.255-30.926， P＝0.025）， while initiating letermovir within 28 days post-transplantation was a protective factor （HR＝0.125， 95%CI of 0.045-0.348， P＜0.001）. CONCLUSIONS Early initiation of letermovir after allo-HSCT significantly reduces the CMV infection rate and delays the onset of infection， with favorable short-term safety.

BACKGROUND:The effect of electroacupuncture on the proliferation and differentiation of hippocampal oligodendrocytes in model mice with Alzheimer's disease remains poorly understood while demyelinating reaction related to oligodendrocytes is a common pathological reaction of Alzheimer's disease. OBJECTIVE:To investigate the effects and mechanism of electroacupuncture stimulation of"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)in Alzheimer's disease model mice on the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes. METHODS:Forty 6-week-old SPF APP/PS1 transgenic male Alzheimer's disease model mice were randomly divided into electroacupuncture group(n=20)and Alzheimer's disease model group(n=20).Healthy male C57BL/6J mice of the same age were used as normal controls(n=20).The mice in the electroacupuncture group received electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)for 16 weeks(20 minutes/day and one day off a week).After electroacupuncture,Morris water maze was used to detect the changes of learning and memory function.Immunohistochemistry was utilized to detect hippocampal dentate gyrus β-amyloid senile plaques.The expression of BrdU/NeuN and BrdU/GALC in the hippocampal dentate gyrus was detected by immunofluorescence double labeling.Western blot assay was used to detect the expression levels of neuron specific protein Nestin and oligodendrocyte specific protein GALC in the hippocampus.mRNA and protein levels of Notch1 and Hes1 in the hippocampus were detected by real-time fluorescence quantitative PCR and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the normal control group,the ability of learning and memory in the Alzheimer's disease model group decreased significantly;hippocampal dentate gyrus β-amyloid senile plaques increased significantly(P<0.01);the expression of GALC and Nestin in the hippocampus decreased significantly(P<0.01,P<0.05).(2)Compared with the Alzheimer's disease model group,the learning and memory ability of the electroacupuncture group was significantly increased;β-amyloid senile plaque in the hippocampal dentate gyrus decreased significantly(P<0.01).BrdU/NeuN double labeled positive cells in the hippocampal dentate gyrus and Nestin protein expression in the hippocampus increased significantly(P<0.01,P<0.05);GALC expression in hippocampus increased significantly(P<0.01).The mRNA and protein levels of Notch1 in the hippocampus were significantly increased(P<0.05,P<0.01).The mRNA and protein levels of Hes1 in the hippocampus decreased significantly(P<0.05).(3)These findings indicate that electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)of the Alzheimer's disease model infant mice can promote the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes,which may be regulated through the Notch1/Hes1 pathway.

Objective To investigate the effect and mechanism of HHQ 16, a derivative of astragaloside Ⅳ, on hepatocyte lipid accumulation. Methods Free fatty acids were used to stimulate lipid hepatocyte accumulation. Triglyceride and Oil Red O staining were detected to reflect hepatocyte lipid accumulation. The expression of α1-acidglycoprotein （ORM） and its regulators were detected by real-time quantitative PCR and immunoblotting. The expression of ORM1 was interfered with siRNA to determine whether it mediated the action of HHQ16.The expression of ORM1 was interfered by siRNA to determine whether it mediated the action of HHQ16. Results HHQ16 significantly ameliorated FFA-induced hepatocyte lipid deposition. HHQ16 elevated ORM expression, and the protective effect of HHQ16 on hepatocyte lipid accumulation was reversed by ORM interference. Conclusion HHQ16 could ameliorate hepatocyte lipid accumulation by elevating ORM.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Objective:This paper is to propose a calibration model based on sine function which enables more choices to determine the functional relationship between the absorbance and the concentration of the tested substance.Methods:This paper uses Taylor series expansion and Levenberg-Marquardt to obtain the optimal parameters for the Sine model and then summarizes the characters of the Sine model. On the basis of these characters, this paper compares and evaluates the experimental data processed by the Sine model from four aspects: correctness, precision, linearity and correlation.Results:The generated sine function calibration model achieved deviations within ±3% of the national standard substance, precision ( CV%) less than 2%, and a linear correlation coefficient greater than 0.990 within the measurement range of 32-710 mg/L. The correlation coefficients between the sine model and other well-performing linear calibration models for 104 clinical samples were all greater than 0.990. Conclusions:The performance evaluation of the prealbumin assay kit using the sine function calibration model meets industry standards and shows good correlation with the results of clinical sample measurements. This indicates that the sine function calibration model can serve as a new calibration model for in vitro diagnostic research and clinical applications.

Objective:To explore the predictive value of preablative stimulated thyroglobulin (psTg) level before 131I treatment on the excellent response (ER) to 131I treatment in patients with functional residual lymph node metastasis without distant metastasis after papillary thyroid carcinoma (PTC) surgery. Methods:From March 2011 to June 2015, 72 patients (22 males, 50 females, age: 14-76 (46.5±14.4) years) who were diagnosed with functional lymph node metastasis without distant metastasis at the time of their first 131I treatment after total thyroid bilobectomy + lymph node dissection performed in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively included, and their serum thyroglobulin antibody (TgAb) levels were normal. Patients were divided into ER group and non-ER group according to the treatment response assessment system. Independent sample t test, χ2 test, and Mann-Whitney U test were used to compare the basic clinical characteristics between the two groups, and then multivariate logistic regression was performed. The ROC curve was employed to evaluate the predictive value of psTg and lymph node size in 131I treatment response. Results:The treatment responses of 44 patients were ER, and those of 28 were non-ER. The differences in gender, age, clinical stage, number and location of postoperative metastatic lymph nodes between ER and non-ER groups were not statistically significant ( t=0.82, χ2 values: 0.16-2.60, all P>0.05), while there were significant differences in American Thyroid Association (ATA) initial risk stratification ( χ2=33.38), lymph node size ( U=296.50) and psTg ( U=111.00, all P<0.001). PsTg (odds ratio ( OR)=0.047, 95% CI: 0.004-0.500, P=0.011) and lymph node size ( OR=0.146, 95% CI: 0.032-0.666, P=0.013) were independent factors affecting ER, whereas ATA initial risk stratification was not an independent factor ( OR=0.266, 95% CI: 0.051-1.390, P=0.116). AUCs for psTg and lymph node size were 0.904 and 0.873, respectively. The cut-off value of psTg was 20.05 μg/L with the sensitivity and specificity of 96.4%(27/28) and 75.0%(33/44) respectively, and lymph node size was 0.75 cm with the sensitivity and specificity of 78.6% (22/28) and 81.8% (36/44) respectively. Conclusion:PsTg can be used to predict 131I outcomes in patients with functional lymph node metastases after PTC, and lymph node size also has effect on ER.

The application indications of imaging examination and cardiac catheterization in the diagnosis, treatment and follow-up of Kawasaki disease, especially cardiovascular sequelae, are further improved by the Japanese Circulation Society/Japanese Society for Cardiovascular Surgery 2020 Guideline on Diagnosis and Management of Cardiovascular Sequelae in Kawasaki Disease that also standardizes the long-term management program of Kawasaki disease in three different stages, namely, school, the adolescent/young adult and adulthood stage.In order to enhance the understanding of domestic medical staff with the latest knowledge, this paper focuses on the application progress of diagnostic imaging and cardiac catheterization in the diagnosis, treatment and long-term management of cardiovascular sequelae of Kawasaki disease in the guide.

Objective:To assess the value of CD4 + and CD8 + T-lymphocyte counts for the diagnostic classification and prognosis of coronavirus disease 2019 (COVID-19). Methods:A total of 95 COVID-19 adult patients admitted to Shanghai Public Health Clinical Center, Fudan University from January to March 2020 were recruited. The CD4 + and CD8 + T-lymphocyte counts among ordinary, severe and critical patients, as well among the cured, improved, unimproved and death patients were compared. The area under receiver operating characteristic curve (AUROC) was used to evaluate the value of CD4 + and CD8 + T-lymphocyte counts for the clinical diagnosis and prognosis of COVID-19. The comparison among groups was performed by Mann-Whitney U test. Results:A total of 95 COVID-19 cases including 68 common, 11 severe and 16 critical cases were enrolled. The counts of CD4 + and CD8 + T-lymphocyte of patients in common, severe and critical groups were 419 (309, 612), 267 (212, 540), 141 (77, 201)/μL, and 238 (153, 375), 128 (96, 172), 92 (51, 144)/μL, respectively, with significant differences ( Z=24.322 and 15.956, respectively, both P<0.01). The counts of CD4 + and CD8 + T-lymphocyte of the death, unimproved, improved, and cured patients were 149 (143, 349), 315 (116, 414), 344 (294, 426), 745 (611, 966)/μL, and 106 (43, 501), 176(67, 279), 194(188, 432), 429(276, 564)/μL, respectively, with significant differences ( Z=36.083 and 16.658, respectively, both P<0.01). The optimal cut-off point of CD4 + T-lymphocyte counts was 237/μL for critical COVID-19 with AUROC 0.911 (95% confidence interval ( CI) 0.833-0.989, P<0.01), with the sensitivity of 86.1% and specificity of 87.5%. For predicting severe and critical cases, the optimal cut-off point of CD4 + T-lymphocyte counts was 405/μL with AUROC 0.863 (95% CI 0.727-0.999, P=0.001), with the sensitivity of 78.6% and specificity of 74.6%. Conclusions:The conditions of patients with COVID-19 are aggravated with CD4 + and CD8 + T-lymphocyte counts decreasing. CD4 + T-lymphocyte counts may be an indicator for diagnostic classification of COVID-19 and prognostic indicator for severe and critical patients.

Objective:To evaluate the clinical value of 125I seed implantation guided by CT in treatment of advanced pancreatic cancer. Methods:The data of 63 patients with advanced pancreatic cancer in the Affiliated Cancer Hospital of Zhengzhou University from Jun. 2015 to Jun. 2018 (48 males and 15 females) were retrospectively analyzed. All patients underwent CT-guided 125I seed implantation, and regular follow-up after operation. All patients were followed up for 3 to 36 months to evaluate the clinical efficacy, including the volume of cancer before and after treatment, tumor marker CA199 and changes in complications such as abdominal pain and jaundice, and the survival status of the patients. Results:Three months after seed implantation, 9 cases (14.3%) had complete remission of cancer in 63 patients, 33 cases had partial remission (52.4%) , 15 cases had no change (23.8%) , and 6 cases had disease progression (9.5%) . The total effective rate was 67.7%. Three months after treatment, the volume of cancer was (31.92±14.93) cm 3, which was significantly smaller than that before treatment [ (44.88±16.19) cm 3; t=6.79, P<0.01]. Three months after treatment, Serum CA199 (77.21±58.69 U/ml) was significantly lower than that before treatment (327.76±110.42) U/ml ( t=16.56, P<0.05) . 125I seed implantation for advanced pancreatic cancer had an average survival period of (13.04±0.92) months and a median delivery period of 11 months. Of the 57 patients with different degrees of abdominal pain, 49 were better than before, and the pain relief rate was 85.9%. Among 42 patients with jaundice symptoms of varying degrees, 31 were better than before, and the jaundice remission rate was 73.8%. There were no serious complications related to treatment in any patients. Conclusion:125I seed implantation therapy can safely and effectively treat advanced pancreatic cancer, and improve related clinical symptoms such as abdominal pain and jaundice.