Objective:To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells(HSCs)after treated by 5-FU in mouse.Methods:Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells(HSPCs)in bone marrow(BM),the proportion of T cells,B cells and myeloid cells(TBM)in peripheral blood(PB)and spleen,and the development of T cells in thymus.Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle,apoptosis and the proportion of HSPCs in BM.The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro.Results:SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice.SIRT5 deletion increased proportion of HSPCs in BM.After 5-FU treatment,the proportion of HSCs in SIRT5 deletion mice was significant decreased(P＜0.05),the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase(P＜0.05),and the proportion of early apoptosis increased(P＜0.05).By monoclonal culture in vitro,the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly(P＜0.05).Conclusion:SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro.SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.

Objective: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient’s resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects Methods: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. Results: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). Conclusion msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β₂-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.
Humans ; Multiple Myeloma/drug therapy* ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Treatment Outcome ; Hematologic Diseases

Urethral stricture is characterized by the chronic formation of fibrous tissue, leading to the narrowing of the urethral lumen. Despite the availability of various endoscopic treatments, the recurrence of urethral strictures remains a common challenge. Postsurgery pharmacotherapy targeting tissue fibrosis is a promising option for reducing recurrence rates. Although drugs cannot replace surgery, they can be used as adjuvant therapies to improve outcomes. In this regard, many drugs have been proposed based on the mechanisms underlying the pathophysiology of urethral stricture. Ongoing studies have obtained substantial progress in treating urethral strictures, highlighting the potential for improved drug effectiveness through appropriate clinical delivery methods. Therefore, this review summarizes the latest researches on the mechanisms related to the pathophysiology of urethral stricture and the drugs to provide a theoretical basis and new insights for the effective use and future advancements in drug therapy for urethral stricture.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Purpose: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results: Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

【Objective】 To investigate the clinicopathological characteristics and prognosis of T2DM patients with renal involvement. 【Methods】 We conducted a retrospective analysis of clinical and pathologic data from T2DM patients who received renal biopsy(n = 120), and these patients were followed up. Renal outcome is defined as receiving renal replacement therapy or progression to ESRD. 【Results】 Among the 120 patients with T2DM, 57(47.5%) were diagnosed as DN, and 63(52.5%) as non diabetic renal disease(NDRD). The most common subtype of NDRD is membranous nephropathy. Compared with the NDRD group, the DN group had longer course of diabetes, worse renal function and higher proportion of diabetic retinopathy. Kaplan-Meier analysis showed that the renal survival rate in DN group was significantly lower than that in NDRD group. The 1-year, 5-year renal survival rate of DN group was only 81%, 41% Vs NDRD group 95, 84%. After multivariate adjustment, the risk of ESRD in DN patients was 3.81 times higher than that of NDRD patients(95%CI 1.61-9.01, P=0.002) . 【Conclusions】 There is a risk of misdiagnosis DN by clinical manifestations, and accurate diagnosis depends on renal biopsy. The prognosis of DN patients is significantly worse than NDRD, so it is of great clinical significance to distinguish the pathological types of diabetic patients with kidney disease.

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
Aged ; China ; epidemiology ; Chlorides ; blood ; Coronary Artery Disease ; blood ; diagnosis ; mortality ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Sodium ; blood

Background:The increasing prevalence of colorectal cancer (CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment.We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods:We conducted a multicenter,cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014.Each enrolled patient was interviewed using a structured questionnaire.All expenditure data were inflated to the 2014 Chinese Yuan (CNY;1 CNY =0.163 USD).We quantified the overall expenditure and financial burden and by subgroup (hospital type,age at diagnosis,sex,education,occupation,insurance type,household income,clinical stage,pathologic type,and therapeutic regimen).We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results:A total of 2356 patients with a mean age of 57.4 years were included,57.1％ of whom were men;13.9％ of patients had stage Ⅰ cancer;and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY,and the expenditures for stage Ⅰ,Ⅱ,Ⅲll,and Ⅳ disease were 56,099 CNY,59,952 CNY,67,292 CNY,and 82,729 CNY,respectively.Non-medical expenditure accounted for 8.3％ of the overall expenditure.The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY,which accounted for 59.9％ of their previous-year household income and caused 75.0％ of families to suffer an unmanageable financial burden.Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups (P ＜ 0.05),except for sex.Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less (all P ＜ 0.05).Conclusions:For patients in China,direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable.The financial burden varied among subgroups,especially among patients with different clinical stages of disease,which suggests that,in China,CRC screening might be cost-effective.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.