Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.

Objectives:To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared.Results:A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods ( P=0.008) . Conclusions:mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.
Child ; Humans ; Infant ; Hepatitis B Vaccines ; Immunization, Secondary ; Hepatitis B Surface Antigens ; Immunologic Memory ; Follow-Up Studies ; Vaccination ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies

OBJECTIVE: To investigate the clinical efficacy and safety of percutaneous foraminal endoscopy in the treatment of lumbar lateral recess stenosis in elderly. METHODS: The clinical data of 31 elderly patients with lumbar lateral recess stenosis treated by percutaneous foraminal endoscopic decompression from March 2018 to August 2019 were retrospectively analyzed. Including 16 males and 15 females, aged from 65 to 81 years with an average of (71.13±5.20) years, the course of disease ranged from 3 months to 7 years with an average of (14.36±6.52) months. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to assess clinical symptom and functional status before operation and 1, 6, 12 months after operation. At the final follow-up, the modified Macnab standard was used to evaluate clinical efficacy. RESULTS: All patients were completed the operation successfully. The operation time was from 75 to 120 min with an average of (97.84±11.22 ) min. All 31 patients were followed up from 12 to 28 months with an average of (17.29±5.56) months. Postoperative lumbago-leg pain VAS and ODI were significantly improved at 1, 6, and 12 months(P<0.01). At the final follow-up, according to the modified Macnab standard to evaluate the effect, 23 got excellent results, 5 good, 3 fair. One patient had severe adhesions between peripheral tissues and nerve root, and postoperative sensory abnormalities in the lower extremities were treated conservatively with traditional Chinese medicine and neurotrophic drugs, which recovered at 2 weeks after surgery. No complications such as nerve root injury and infection occurred. CONCLUSION The intervertebral foraminal endoscopy technique, which is performed under local anesthesia for a short period of operation, ensures adequate decompression while minimizing complications, and is a safe and effective surgical procedure for elderly patients with lumbar lateral recess stenosis.
Male ; Female ; Humans ; Aged ; Infant ; Constriction, Pathologic/surgery* ; Spinal Stenosis/surgery* ; Decompression, Surgical/methods* ; Retrospective Studies ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Treatment Outcome

AIM: To examine the effects of salidroside on choroidal thickness, hypoxia-inducible factor-1α(HIF-1α), dopamine(DA)and its D1 receptor expression in guinea pigs with lens-induced myopia(LIM).METHODS: A total of 18 two-week-old guinea pigs were randomly divided into the normal control(NC)group, the LIM group, and the LIM + salidroside(LIM+SA)group, with 6 guinea pigs in each group. The guinea pigs in the NC group were fed normally and intragastrically administered with 2 mL/d saline; those in the LIM group wore a -5D lens in front of their right eyes to establish a myopia model, then they were intragastrically administered with 2 mL/d saline. Finally, those in the LIM+SA group wore glasses along with intragastric administration of 2 mL/d salidroside at a dose of 100 mg/kg. The refraction, axial length, and choroidal thickness of guinea pigs in each group were measured 4wk following the establishment of the model. In addition, the relative mRNA expression and protein content of HIF-1α in the choroid and retina of guinea pigs in each group were detected by real-time quantitative PCR(qPCR)and immunohistochemistry(IHC). Finally, the DA concentration and its D1 receptor expression were detected by enzyme-linked immunosorbent assay(ELISA)and Western blot.RESULTS: At 4wk after model establishment, guinea pigs of LIM group and LIM+SA group exhibited increased negative refraction of the right eye, prolonged axial length, and decreased choroidal thickness compared to the NC group. The relative mRNA expression and protein content of HIF-1α in the choroid and retina of the guinea pigs increased. The concentration of DA and the expression of its D1 receptor both decreased. Moreover, compared to the LIM group, the diopter of the right eye of guinea pigs in LIM+SA group significantly reduced, the axial length was shorter, the thickness of choroid increased, the relative mRNA expression and protein content of HIF-1α in the choroid and retina decreased and the concentration of DA and the expression of its D1 receptor both increased.CONCLUSION: Salidroside can delay myopia progression in myopic guinea pigs by affecting choroidal thickness and the expression of HIF-1α, DA and its D1 receptor.

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

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve^® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve^® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve^® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve^® system.
Aged ; Aged, 80 and over ; Aortic Valve ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Prospective Studies ; Transcatheter Aortic Valve Replacement/methods* ; Treatment Outcome

OBJECTIVE: The individual cascades of the insulin-like growth factor-1 (IGF-1) signaling pathway and the molecular mechanism of aging have not been fully clarified. In the current study, we explored the effect of DNA polymerase delta 1 (POLD1) on the IGF-1 signaling pathway in cell aging. METHODS: First, we analyzed the relationship between IGF-1 and POLD1 expression in aging. To investigate the effect of IGF-1 on POLD1 expression and aging, the 2BS cells were incubated with young-age or old-age human serum, IGF-1 protein, or linsitinib. Next, the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism. RESULTS: In this study, we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice, and a negative relationship between IGF-1 and POLD1 expression was observed. Furthermore, the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics, and the effect could be reversed by treatment with linsitinib or overexpression of POLD1, while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1. CONCLUSION Taken collectively, our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1. These findings offer a new target for anti-aging strategies.
Humans ; Animals ; Mice ; Insulin-Like Growth Factor I/pharmacology* ; Cellular Senescence ; Aging ; Hippocampus ; DNA Polymerase III

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage