OBJECTIVES: To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy. METHODS: A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed. RESULTS: The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05). CONCLUSIONS CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Antifungal Agents/therapeutic use* ; Candidiasis/diagnosis* ; Chronic Disease ; Leukemia/complications* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications* ; Prognosis ; Retrospective Studies

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

ObjectiveTo analyse the clinical characteristics of different traditional Chinese medicine （TCM） syndromes in patients with heart failure based on information from electronic medical record. MethodsA cross-sectional study was conducted to collect clinical data of all inpatients with heart failure in the Department of Cardiology， Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 1， 2019 to December 31， 2020. A database of clinical TCM data was established to explore the characteristics of clinical data of basic information， syndromes and syndrome element types， and biochemical indexes. The distribution of TCM syndromes and syndrome elements in heart failure patients were also analysed， and the basic information and biochemical indexes of the patients with top 7 different TCM syndrome types were compared. ResultsA total of 1676 inpatients with heart fai-lure were included. The top 7 TCM syndromes of heart failure were syndrome of phlegm turbidity and blood stasis （477 cases， 28.46%）， syndrome of qi deficiency and blood stasis （439 cases， 26.19%）， syndrome of qi deficiency and blood stasis with water retention （274 cases， 16.35%）， syndrome of yang deficiency with water retention （145 cases， 8.65%）， syndrome of qi and yin deficiency （104 cases， 6.21%）， syndrome of qi and yin deficiency with blood stasis （80 cases， 4.77%）， syndrome of heart yang deficiency （59 cases， 3.52%）. Among the 1676 patients， 6 syndrome elements accounted for more than 5%. Blood stasis accounted for the highest proportion of TCM syndrome element type （1292 cases， 77.09%）， followed by qi deficiency （919 cases， 54.83%）， phlegm （498 cases， 29.71%）， water retention （434 cases， 25.89%）， yang deficiency （215 cases， 12.82%） and yin deficiency （191 cases， 11.40%）. Among the 1676 patients， 1308 cases of acute heart failure mainly showed syndrome of phlegm turbidity and blood stasis （386 cases， 29.51%）， and 368 of chronic heart fai-lure mainly showed syndrome of qi deficiency and blood stasis （118 cases， 32.07%）. Patients with syndrome of phlegm turbidity and blood stasis had the shortest disease duration of 0.3 months， while those with syndrome of heart yang deficiency had the longest disease duration of 15 months. The proportion of syndrome of phlegm turbidity and blood stasis was the highest in patients with heart failure combined with coronary artery disease， the proportion of syndrome of qi deficiency and blood stasis with water retention was the highest in patients with heart failure combined with atrial fibrillation， and the proportion of patients with syndrome of qi deficiency and blood stasis with water retention and syndrome of yang deficiency with water retention in those applying diuretics during the hospital stay was the highest with more than 86%. The different 7 TCM syndromes showed statistically difference in patients with complications including coronary artery disease， old myocardial infarction， atrial fibrillation， pre and post-admission medication usage including intravenous vasodilators， cardiac stimulants， diuretics， and level of blood chloride， blood urea， blood creatinine， blood bicarbonate， blood albumin， and blood total bilirubin （P＜0.05）. ConclusionThe most common TCM syndromes in patients with heart failure are syndrome of phlegm turbidity and blood stasis and syndrome of qi deficiency and blood stasis. Different TCM syndromes have different characteristics in gender， disease complications， medication before and after admission， and blood indexes.

Objective:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0.Methods:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results:The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.

The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3∶1, 5∶1, 10∶1, and 15∶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 μm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 μm were significantly and positively correlated with J_2. NSTs with a length of 200-600 μm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.
Trichomes ; Moxibustion ; Hot Temperature ; Plant Leaves

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.
Male ; Humans ; Prostatic Neoplasms/chemically induced* ; Androgen Antagonists/adverse effects* ; COVID-19 ; Androgens/therapeutic use* ; SARS-CoV-2

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.