OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To retrospectively analyze the clinical characteristics of 15 children with B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab, and summarize the efficacy and safety of blinatumomab in the treatment of pediatric B-ALL. METHODS: Fifteen children who received treatment with blinatumomab from February 2022 to January 2023 were enrolled in this study. One course (28 days) of blinatumomab concurrent with intrathecal chemotherapy was given according to the standard regimen, except for 2 cases who had shortened course of treatment due to hematopoietic stem cell transplantation (HSCT) and did not receive combined intrathecal chemotherapy, and 1 case had a shortened course of treatment due to economic problems. The efficacy and safety of the treatment were evaluated. RESULTS: In terms of efficacy, for the children who had achieved complete molecular remission (CMR) before treatment, blinatumomab treatment could effectively maintain CMR status; For the children who did not achieve CMR, the CMR rate after one standard course of treatment with blinatumomab reached 66.7%(4/6); For the children with relapsed/refractory ALL (R/R ALL) who had minimal residual disease (MRD), the MRD clearance rate reached 75.0%(3/4). The statistical results of the incidence of adverse events showed that 13.3%(2/15) of the children did not experience any adverse events. The most common adverse events were cytokine release syndrome (CRS) (73.3%, 11/15) and transaminase elevation (26.7%, 4/15); 33.3%(5/15) of the children experienced grade 3 or higher adverse events. All the adverse events were resolved after symptomatic treatment.The level of IgG decreased significantly after 4-7 weeks of treatment with blinatumomab, and gradually recovered after 8 weeks of treatment. CONCLUSION Blinatumomab can be used as a safe and effective treatment for inducing deep remission in pediatric R/R-ALL patients and as a bridge therapy for the pediatric ALL patients who are intolerant to chemotherapy.
Humans ; Antibodies, Bispecific/therapeutic use* ; Child ; Retrospective Studies ; Female ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Remission Induction ; Treatment Outcome ; Child, Preschool ; Adolescent ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

OBJECTIVES: To investigate the relationship between hypothermia duration and postoperative complications in patients undergoing gynecological surgery. METHODS: Patients who underwent elective gynecological surgery at our hospital were consecutively enrolled between October 2020 and January 2022. Core temperature was continuously monitored intraoperatively, and early postoperative complications were collected. By adjusting the logistic regression model for potential confounding factors, the association of postoperative complications with the duration of hypothermia, the lowest body temperature below 36°‍C, and the hypothermia upon admission to postanesthesia care unit (PACU) or intensive care unit (ICU) were analyzed. Additionally, the potential inflection point in the relationship between the duration of hypothermia and the risk of postoperative complications was explored by using cumulative probability scatter plots and moving average sequences. RESULTS: The study included 370 patients, with 193 (52.2%) experiencing hypothermia and 177 (47.8%) not. Among them, 92 (24.9%) developed complications. The duration of hypothermia (adjusted odds ratio [OR] for each one-minute increase: 1.003; 95% confidence interval [CI]: 1.000-1.006, P=0.047) and hypothermia upon admission to PACU or ICU (adjusted OR: 1.980; 95% CI: 1.135-3.454, P=0.016) were associated with early postoperative complications. Notably, the cumulative incidence of postoperative complications tended to rise as the duration of hypothermia increased, with a potential inflection point observed at 120 minutes. CONCLUSIONS In gynecological surgery, the duration of hypothermia as well as hypothermia upon admission to PACU or ICU are associated with postoperative complications. Minimizing the duration of hypothermia may be clinically beneficial.
Humans ; Female ; Hypothermia/epidemiology* ; Postoperative Complications/etiology* ; Gynecologic Surgical Procedures/adverse effects* ; Prospective Studies ; Middle Aged ; Adult ; Intensive Care Units ; Time Factors ; Aged

OBJECTIVE: To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF). METHODS: Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO₂), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups. RESULTS: After the 12-week intervention, patients in group C showed significant declines in peakVO₂, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO₂, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO₂, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01). CONCLUSIONS Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).
Humans ; Heart Failure/therapy* ; Quality of Life ; Stroke Volume ; Exercise

Objective: To evaluate the effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant. Methods: A total of 1 403 Omicron-infected patients admitted to 20 designated hospitals in Guangdong Province from January 1 to May 31, 2022, were selected as subjects in this study. A case-control study was conducted to collect the demographic data, underlying disease, vaccination status, last exposure date, gene sequencing of infected strains and clinical outcomes from the China Disease Prevention and Control Information System and Guangdong telemedicine platform. Pneumonia (common, severe and critical) and non-pneumonia (asymptomatic and mild) were selected as the case group and control group. The effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant was analyzed. Results: The median age [M (Q₁, Q₃)] of the subjects was 36 (27-47) years old, with males accounting for 52.25% (733 cases). The main outcome of the infection was non-pneumonia, accounting for 92.09% (1 292 cases), and the duration [M (Q₁, Q₃)] of the disease was 18 (14-22) days. There were 134 (9.55%), 39 (2.78%), 403 (28.72%), 437 (31.15%) and 390 (27.80%) cases with no or partial vaccination, within 90 days of primary vaccination, over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination, respectively. Multivariate logistic regression analysis showed that after adjusting for gender, age, underlying disease, and location of the report, compared with those with no or partial vaccination, the risk of developing pneumonia was lower in those with over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination [OR (95%CI) values were 0.52 (0.28-0.98), 0.39 (0.21-0.73) and 0.40 (0.21-0.77), respectively]. Cox proportional hazard regression model analysis showed that after adjusting for gender, age, underlying disease and location of the report, the duration of the disease was shorter in those who received booster vaccinated for more than 90 days compared with that in those who had no or partial vaccination [HR (95%CI): 1.26 (1.03-1.55)]. Conclusion: The inactivated SARS-CoV-2 vaccine affects the clinical outcomes of patients infected with the Omicron variant.
Adult ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China/epidemiology* ; COVID-19/prevention & control* ; COVID-19 Vaccines ; SARS-CoV-2 ; Female

Objective: To investigate the prospective association of physical activity with all-cause, cardiovascular disease (CVD), and chronic kidney disease (CKD) mortality in CKD patients in China. Methods: Cox proportional hazard models were used to evaluate the association of total, domain-specific, and intensity-specific physical activity with the risk of all-cause, CVD, and CKD mortality based on data from the baseline survey of China Kadoorie Biobank. Results: During a median follow-up of 11.99 (11.13, 13.03) years, there were 698 deaths in 6 676 CKD patients. Compared with the bottom tertile of total physical activity, participants in the top tertile had a lower risk of all-cause, CVD, and CKD mortality, with hazard ratios (HRs) (95%CIs) of 0.61 (0.47-0.80), 0.40 (0.25-0.65), and 0.25 (0.07-0.85), respectively. Occupational, commuting, and household physical activity were negatively associated with the risk of all-cause and CVD mortality to varying degrees. Participants in the top tertile of occupational physical activity had a lower risk of all-cause (HR=0.56, 95%CI: 0.38-0.82) and CVD (HR=0.39, 95%CI: 0.20-0.74) mortality, those in the top tertile of commuting physical activity had a lower risk of CVD mortality (HR=0.43, 95%CI: 0.22-0.84), and those in the top tertile of household physical activity had a lower risk of all-cause (HR=0.61, 95%CI: 0.45-0.82), CVD (HR=0.44, 95%CI: 0.26-0.76) and CKD (HR=0.03, 95%CI: 0.01-0.17) mortality, compared with the bottom tertile of corresponding physical activity. No association of leisure-time physical activity with mortality was observed. Both low and moderate-vigorous intensity physical activity were negatively associated with the risk of all-cause, CVD and CKD mortality. The corresponding HRs (95%CIs) were 0.64 (0.50-0.82), 0.42 (0.26-0.66) and 0.29 (0.10-0.83) in the top tertile of low intensity physical activity, and the corresponding HRs (95%CIs) were 0.63 (0.48-0.82), 0.39 (0.24-0.64) and 0.23 (0.07-0.73) in the top tertile of moderate-vigorous intensity physical activity. Conclusion: Physical activity can reduce the risk of all-cause, CVD, and CKD mortality in CKD patients.
Humans ; Exercise ; Motor Activity ; Cardiovascular Diseases ; China ; Renal Insufficiency, Chronic

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To investigate the introduction of vegetables and fruits in 4-8 months old infants, and to describe the maternal and infants' characteristics associated with the introduction of vegetables and fruits. METHODS: Mother-infant dyads (n=228) were recruited from 12 to 16 weeks postpartum and formally entered the study at 4 months of age. Data collected via face to face interview at 4-8 months postpartum, including the timing and types of added vegetables and fruits, as well as a variety of maternal and infant characteristics (n=204). Rank sum test and multiple linear regression were used to analyze the maternal and infant characteristics related to the introduction of vegetables and fruits. RESULTS: The time of introducing vegetables was concentrated at the age of 7 months, and the time of adding fruits was mainly at 6 months. Fruits were added earlier than vegetables (P < 0.001), and the variety of the added fruits was higher than that of vegetables (P=0.045). 48% (n=98) of infants had no more than three types of fruits and vegetables at 8 months. Only 9.8% (n=20) had added more than 10 kinds of fruits and vegetables at 8 months. Green leafy vegetables were the most commonly added vegetable, and apple was the most popular fruit. Compared with women who were 35 years of age or younger, women beyond 35 years old introduced vegetables to their babies 0.6 months later. 4-month-old exclusively breastfed infants had vegetables 0.4 months later than mixed-fed infants. Women with a bachelor's degree or above added 2-3 more types of fruits and vegetables to their babies than those with junior high school education and below. CONCLUSION The adding time of fruits was earlier than that of vegetable. Apples and green leafy vegetables are commonly added. Women with lower educational backgrounds add fewer types of fruits and vegetables to their babies. Mothers who choose exclusive breastfeeding and those over 35 years of age at childbirth add vegetables to their babies later than others. They should be targeted for health promotion programs that aim to improve the intake of fruits and vegetables among infants.
Adult ; Beijing ; Breast Feeding ; Female ; Follow-Up Studies ; Fruit ; Humans ; Infant ; Infant, Newborn ; Vegetables