Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Objective To evaluate the long-term efficacy of tumor necrosis factor-α(TNF-α)inhibitor(TNFi)in the treatment of ankylosing spondylitis(AS)complicated with osteoporosis(OP)and the impact on bone metabolism,bone density,and inflammatory factors.Methods The data of 158 patients with AS and OP,who were admitted to Department of Rheumatology and Immunology of The First Affiliated Hospital of Naval Medical University(Second Military Medical University)from Jan.1,2010 to Dec.31,2017,were retrospectively collected.The patients were divided into bisphosphonate group(n=54),TNFi group(n=58),and TNFi+bisphosphonate group(n=46)according to the treatment methods.All patients were treated with calcium combined with calcitriol as the background treatment.After 5 years of treatment,Bath ankylosing spondylitis disease activity index(BASDAI)and Bath ankylosing spondylitis functional index(BASFI)scores were evaluated,and inflammatory indexes,bone metabolism markers,and bone mineral density were detected.Results After 5 years of treatment,the BASDAI and BASFI scores,erythrocyte sedimentation rate(ESR),C reactive protein(CRP),TNF-α,and interleukin-17A of the TNFi+bisphosphonate group and TNFi group were significantly lower than those before treatment(all P＜0.05);in the bisphosphonate group only ESR and CRP were significantly lower than those before treatment(both P＜0.05),and the other inflammatory indexes and BASDAI and BASFI scores showed no significant changes(all P＞0.05).The bone mineral density of the 3 groups after 5 years of treatment was significantly higher than that before treatment(all P＜0.05),and the bone mineral density of the TNFi+bisphosphonate group was significantly higher than that of the other 2 groups(both P＜0.05).After 5 years of treatment,the levels of parathyroid hormone(PTH),procollagen type 1 N-terminal propeptide(P1NP)and β-C-terminal telopeptide of type Ⅰ collagen(β-CTX)in the TNFi+bisphosphonate group and bisphosphonate group were significantly decreased compared with those before treatment(all P＜0.05),while the levels of N-terminal midfragment of osteocalcin(N-MID)and 25-hydroxy-vitamin D(25VitD)were significantly increased(all P＜0.05);in the TNFi group only PTH and P1NP levels were significantly decreased(both P＜0.05),while β-CTX,N-MID and 25VitD levels showed no significant differences(all P＞0.05).Conclusion Long-term use of TNFi in patients with AS and OP can effectively reduce disease activity,improve physical function,decrease the level of inflammatory factors,alleviate abnormal bone metabolism,and increase bone mineral density;and the combined use of TNFi and bisphosphonates has better efficacy.

Objective:To carry out an overview of systematic reviews on interventions to prevent the recurrence of diabetic foot ulcer (DFU) patients.Methods:Systematic reviews or Meta-analysis on interventions to prevent DFU recurrence were electronically retrieved from databases such as China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc, Joanna Briggs Institute (JBI) Evidence-Based Healthcare Center Database, Cochrane Library, PubMed, Embase, CINAHL and Web of Science. The search period was from database establishment to April 20, 2023. Two researchers independently searched and screened literature, and extracted data, and used AMSTAR 2 software and the quality evaluation criteria for systematic review of JBI Evidence-Based Healthcare Center to evaluate the methodological quality of the included literature. GRADE evaluation system was used for quality assessment of outcome indicators (DFU recurrence rate, effectiveness of measures to prevent DFU recurrence) .Results:A total of 24 systematic reviews were included. Studies showed that monitoring and intervention of foot skin temperature, therapeutic shoes or insoles, comprehensive intervention measures, and specific surgical methods could reduce the recurrence rate of DFU, while foot self-care, foot exercise, health education, and psychological intervention had no statistical effect on preventing DFU recurrence. The methodological quality of systematic reviews was generally low. The reports of four articles were relatively complete, 18 articles had certain defects, and two articles had serious defects. The evaluation of evidence quality showed that there were three pieces of moderate-quality evidence, seven pieces of low-quality evidence, and 30 pieces of extremely low-quality evidence.Conclusions:Existing evidence suggests that foot skin temperature monitoring and intervention, therapeutic shoes or insoles, comprehensive intervention measures, and specific surgical methods (such as Achilles tendon lengthening, metatarsophalangeal joint replacement, metatarsal head resection and so on) have a positive impact on preventing DFU recurrence. Rigorous and high standard research is still needed to verify the controversial issues, so as to provide reliable evidence for future clinical practice and studies.

Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(＜5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(＞8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P＜0.05),while the levels of fibrinogen decrease(P＜0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P＜0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P＜0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin＞5 000 μg/L,β2-microglobulin＞7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

Objective:To analyze the genetic evolution and molecular characteristics of H7N9 avian influenza virus (AIV) isolated in a live poultry market.Methods:Samples such as poultry feces, sewage, and hair removal machine and chopping board swabs were collected. Real-time fluorescent quantitative PCR was used to detect influenza A virus and H7N9 AIV in the samples. The whole genome of H7N9 AIV was amplified with influenza A virus universal primers and sequenced. BLAST and MEGA X were used for sequence alignment, phylogenetic analysis and molecular characterization.Results:Seven poultry-related environment samples were collected in the live poultry market in Xuchang city in February 2023, and four were positive for H7N9 AIV. The whole genome sequences of three H7N9 AIV isolates were successfully obtained, and the isolates shared high nucleotide identity in different genes (98.37%-100.00%). BLAST analysis showed they were highly identical to H7N9 strains isolated from domestic poultry in China from 2020 to 2021. Genetic evolution analysis showed that the three isolates clustered in the same branch and were closer to the recent environmental isolates than to the recent strains isolated from human or avian. Through comparison with the sequences of the representative strains in different periods, it was found that the isolated strains in this study showed high avian pathogenicity with four amino acids KRAA inserted at the cleavage site; the hemagglutinin receptor-binding site was QSG, which was an avian binding receptor; there was a G186I mutation in hemagglutinin. Mammalian-adaptive mutation E627K was not detected in polymerase basic protein 2. Mutations (R292K and I38T) associated with drug resistance to neuraminidase inhibitor (oseltamivir) and polymerase acidic protein inhibitor (baloshavir) were not detected, suggesting that these isolates remained susceptible to these drugs. A S31N mutation was found in M2 protein, indicating they were resistant to alkamines.Conclusions:The three H7N9 AIV strains isolated in the live poultry market have high avian pathogenicity, but there are no significant increase in mutations related to the binding ability to human receptors, mammalian pathogenicity, viral transmissibility, or drug resistance as compared with previous representative strains causing human or avian infection.

Abstract: Objective　To analyze the influencing factors of mother-to-child transmission of hepatitis B virus after combined immunological blockade, and to evaluate the effect of mother-to-child blockade, and to provide a basis for health policies and health interventions for preventing mother-to-child blockade of hepatitis B virus. Methods A total of 11 363 pairs of HBsAg positive pregnant women and their infants aged 7-12 months in Hainan Province from 2015 to 2020 were included in the study. The general situation, the situation of health care and delivery in this pregnancy and perinatal period, the detection of hepatitis B markers, the situation of antiviral therapy, the general situation of mother and infant during delivery and the implementation of blockade measures for mother-to-child transmission of hepatitis B were collected and analyzed. Results Among the 11 363 pairs of HBsAg positive pregnant women and their infants delivered in hospitals in Hainan province from 2015 to 2020, the positive rate of HBsAg in children at 7-12 months after birth was 1.47 %, and the difference in HBsAg positive rate of infants born in different years was not statistically significant (P>0.05). There were no significant differences in the positive rate of HBsAg among children born to pregnant women with different nationalities, educational levels, occupations, delivery modes, delivery places, obstetric operations and perineal laceration, abnormal perinatal period, children with different genders and premature delivery and perinatal (all P<0.05). There was significant difference in HBsAg positive rate among infants born to pregnant women of different ages, the positive rate of HBsAg of infants born to young pregnant women was higher than that of older pregnant women (P<0.05). The rate of antiviral therapy was low in HBeAg positive pregnant women, and the positive rate of HBsAg in their infants was 2.54%, which was higher than 0.83% in HBeAg negative pregnant women (P<0.05). Conclusions Combined immunological blockade with hepatitis B vaccine and hepatitis B immunoglobulin can effectively prevent the mother-to-child transmission of HBV. HBsAg-positive women can give birth at the right age, and HBeAg-positive pregnant women can be treated with antiviral therapy to block mother-to-child transmission, providing the important basis for the formulation of hepatitis B prevention and control strategies and measures.

Humans ; Coal ; Dust/analysis* ; Anthracosis ; China/epidemiology* ; Coal Mining ; Occupational Exposure

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans ; U937 Cells ; RUNX1 Translocation Partner 1 Protein ; Leukemia/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Oncogene Proteins, Fusion/genetics* ; Leukemia, Myeloid, Acute/genetics*

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

To develop a caregiver parenting behavior scale for children aged 2 to 6 years, and to verify its reliability and validity. This study recruited 1 350 caregivers of children aged 2 to 6 years. The item discrimination analysis and exploratory factor analysis were used to analyze the structure, dimensions and items of the scale. Homogeneity reliability, split-half reliability and test-retest reliability were used to analyze the reliability of the scale. Content validity and construct validity were used to analyze the validity of the scale. The results showed that the final scale contained 7 dimensions and 45 items. Cronbach's α coefficient of the total scale was 0.945; the coefficient of split half was 0.899; the test-retest reliability analysis showed that the correlation coefficients between the two tests were 0.893 (total score), 0.854 (social), 0.832 (language), 0.871 (gross motor), 0.893 (fine motor), 0.862 (cognitive), 0.832 (self-care), and 0.872 (sensory). The content validity analysis was carried out by two rounds of expert argumentation using Delphi expert consultation method. The Kendall coefficient of the items score in two rounds of Delphi expert consultation was 0.813 (P<0.01). The structure validity analysis showed that there were significant correlations between each dimension and the total scale, also between each dimension of the scale, and the extracted average variance values of each dimension was greater than the correlation coefficients between this dimension and other dimensions. In conclusion, the reliability and validity of the scale are qualified. It can be used as a tool to evaluate and guide the parenting behavior of caregivers of children aged 2 to 6 years.
Humans ; Child ; Caregivers/psychology* ; Reproducibility of Results ; Parenting ; Surveys and Questionnaires ; Factor Analysis, Statistical ; Psychometrics/methods*