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BackgroundHigh-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy.MethodsTreatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3–4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®).ResultsHere, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3–4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF.ConclusionOur findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

Photocatalytic degradation has been extensively investigated toward the removal emerging contaminants (ECs) from water. In this study, a series of Ag-Bi3O4Cl plasmon photocatalysts were synthesized through the photo-deposition of metallic Ag on the Bi3O4Cl surface. The effects of plasmon modification on the catalytic performance of bismuth oxychlorides were analyzed. Ag addition did not alter the morphology of Bi3O4Cl. With the increasing Ag content, the number of oxygen defects on the catalyst surface first increased and then decreased. Moreover, the surface plasmon resonance effect of Ag suppressed the recombination of electron–hole pairs, promoting the migration and separation of photocarriers and improving the light absorption efficiency. However, the addition of excessive Ag reduced the number of active sites on the Bi3O4Cl surface, hindering the catalytic degradation of pollutants. The optimal Ag-Bi3O4Cl photocatalyst (Ag ratio: 0.025; solution pH: 9; dosage: 0.8 g/L) achieved 93.8 and 94.9% removal of ciprofloxacin and tetrabromobisphenol A, respectively. The physicochemical and photoelectric properties of Ag-Bi3O4Cl were determined through various characterization techniques. This study demonstrates that introducing metallic Ag alters the electron transfer path of the catalyst, reduces the recombination rate of electron–hole pairs, and effectively improves the catalytic efficiency of Bi3O4Cl. Furthermore, the pathways of ciprofloxacin degradation products and their biotoxicity were revealed.

BackgroundProgrammed death receptor 1 (PD-1) inhibition has shown durable response and mild adverse events (AEs) in adult malignancies. However, data on the clinical activity of PD-1 inhibition in pediatric patients are lacking. We comprehensively assessed the efficacy and safety of PD-1 inhibitor-based regimens for pediatric malignancies.MethodsWe conducted a real-world, multi-institutional, retrospective analysis of pediatric malignancies treated with PD-1 inhibitor-based regimens. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints included disease control rate (DCR), duration of response (DOR), and AEs. The Kaplan–Meier method was used to calculate PFS and DOR. The National Cancer Institute Common Toxicity Criteria for AEs (version 5.0) were used to grade toxicity.ResultsA total of 93 and 109 patients were evaluated for efficacy and safety, respectively. For all efficacy-evaluable patients, PD-1 inhibitor monotherapy, combined chemotherapy, combined histone deacetylase inhibitor, and combined vascular endothelial growth factor receptor tyrosine kinase inhibitor cohorts, the ORR and DCR were 53.76%/81.72%, 56.67%/83.33%, 54.00%/80.00%, 100.00%/100.00%, and 12.50%/75.00%, respectively; the median PFS and DOR were 17.6/31.2 months, not achieved/not achieved, 14.9/31.2 months, 17.6/14.9 months, and 3.7/1.8 months, respectively; the incidence rate of AEs were 83.49%, 55.26%, 100.00%, 80.00%, and 100.00%, respectively. One patient in the PD-1 inhibitor-combined chemotherapy cohort discontinued treatment due to diabetic ketoacidosis.ConclusionsThis largest retrospective analysis demonstrate that PD-1 inhibitor-based regimens are potentially effective and tolerable in pediatric malignancies. Our findings provide references for future clinical trials and practice of PD-1 inhibitors in pediatric cancer patients.

Introduction: Metronomic maintenance therapy (MMT) has significantly improved the survival of patients with high-risk rhabdomyosarcoma in clinical trials. However, there remains a lack of relevant data on its effectiveness in real-world situations.Methods: We retrospectively retrieved data of 459 patients < 18 years of age diagnosed with rhabdomyosarcoma at Sun Yat-sen University Cancer Center from January 2011 to July 2020 from our database. The MMT regimen was oral vinorelbine 25–40 mg/m2 for twelve 4-week cycles on days 1, 8, and 15, and oral cyclophosphamide 25–50 mg/m2 daily for 48 consecutive weeks.Results: A total of 57 patients who underwent MMT were included in the analysis. The median follow-up time was 27.8 (range: 2.9–117.5) months. From MMT to the end of follow-up, the 3-year PFS and OS rates were 40.6% ± 6.8% and 58.3% ± 7.2%, respectively. The 3-year PFS was 43.6% ± 11.3% in patients who were initially diagnosed as low- and intermediate-risk but relapsed after comprehensive treatment (20/57), compared with 27.8% ± 10.4% in high-risk patients (20/57) and 52.8% ± 13.3% in intermediate-risk patients who did not relapse (17/57). The corresponding 3-year OS for these three groups was 65.8% ± 11.4%, 50.1% ± 12.9%, and 55.6% ± 13.6%, respectively.Conclusion: We present a novel study of MMT with oral vinorelbine and continuous low doses of cyclophosphamide in real-world pediatric patients with RMS. Our findings showed that the MMT strategy significantly improved patient outcomes and may be an effective treatment for high-risk and relapsed patients.

BackgroundMethadone maintenance treatment (MMT) is a common treatment for heroin use disorder (HUD). Although individuals with HUD have been reported to show impaired coupling among the salience network (SN), executive control network (ECN), and default mode network (DMN), the effects of MMT on the coupling among three large-scale networks in individuals with HUD remains unclear.MethodsThirty-seven individuals with HUD undergoing MMT and 57 healthy controls were recruited. The longitudinal one-year follow-up study aimed to evaluate the effects of methadone on anxiety, depression, withdrawal symptoms and craving and number of relapse, and brain function (SN, DMN and bilateral ECN) in relation to heroin dependence. The changes in psychological characteristics and the coupling among large-scale networks after 1 year of MMT were analyzed. The associations between the changes in coupling among large-scale networks and psychological characteristics and the methadone dose were also examined.ResultsAfter 1 year of MMT, individuals with HUD showed a reduction in the withdrawal symptom score. The number of relapses was negatively correlated with the methadone dose over 1 year. The functional connectivity between the medial prefrontal cortex (mPFC) and the left middle temporal gyrus (MTG; both key nodes of the DMN) was increased, and the connectivities between the mPFC and the anterior insular and middle frontal gyrus (key nodes of the SN) were also increased. The mPFC-left MTG connectivity was negatively correlated with the withdrawal symptom score.ConclusionLong-term MMT enhanced the connectivity within the DMN which might be related to reduced withdrawal symptoms, and that between the DMN and SN which might be related to increase in salience values of heroin cues in individuals with HUD. Long-term MMT may be a double-edged sword in treatment for HUD.

The endoplasmic reticulum (ER) is the largest tubular reticular organelle spanning the cell. As the main site of protein synthesis, Ca2+ homeostasis maintenance and lipid metabolism, the ER plays a variety of essential roles in eukaryotic cells, with ER molecular chaperones participate in all these processes. In recent years, it has been reported that the abnormal expression of ER chaperones often leads to a variety of neurodevelopmental disorders (NDDs), including abnormal neuronal migration, neuronal morphogenesis, and synaptic function. Neuronal development is a complex and precisely regulated process. Currently, the mechanism by which neural development is regulated at the ER level remains under investigation. Therefore, in this work, we reviewed the recent advances in the roles of ER chaperones in neural development and developmental disorders caused by the deficiency of these molecular chaperones.

High-risk neuroblastoma (NB) is sensitive to chemotherapy but susceptible to chemoresistance. In this study, we aimed to analyze the incidence of chemoresistance in high-risk NB patients and to explore the role of autophagy in NB chemoresistance. We retrospectively analyzed the incidence of changing the chemotherapy regimen due to disease stabilization or disease progression during induction chemotherapy in high-risk NB patients, which was expressed as the chemoresistance rate. The autophagy levels were probed in tumor cells exposed to first-line chemotherapy agents. The sensitivity of tumor cells to chemotherapy agents and apoptosis rate were observed after inhibiting autophagy by transfection of shRNA or chloroquine (CQ). This study included 247 patients with high-risk NB. The chemoresistance rates of patients treated with cyclophosphamide + adriamycin + vincristine (CAV) alternating with etoposide + cisplatin (EP) (Group 1) and CAV alternating with etoposide + ifosfamide + cisplatin (VIP) (Group 2) was 61.5% and 39.9% (P = 0.0009), respectively. Group 2 had better survival rates than group 1. After exposure to cisplatin, cyclophosphamide, and etoposide, the autophagy-related proteins LC3-I, LC3-II, and Beclin-1 were upregulated, and the incidence of autophagy vesicle formation and the expression of P62 were increased. Chemotherapeutic agents combined with CQ significantly increased the chemotherapeutic sensitivity of tumor cells and increased the cell apoptosis. The downregulated expression of Beclin-1 increased the sensitivity of tumor cells to chemotherapeutics. Our results suggest that increasing the chemotherapy intensity can overcome resistance to NB. Inhibition of autophagy is beneficial to increase the sensitivity of NB to chemotherapy agents.

Epichlorohydrin (ECH) is toxic to humans via multiple routes and is a potential carcinogen. The accurate measurement of ECH at trace level (

This paper overviews progress in the research of water mass classification in the China seas, consisting of the Bohai Sea, the Yellow Sea, the East China Sea, the Taiwan Strait and the South China Sea. So far, oceanographers have achieved systematic research results in terms of the concept and definition, theory and method, characteristics and variation of water masses in the China seas. Here 3-D visualized diagrams are developed to illustrate spatial distributions of classified water masses in the China seas. Meanwhile, core values or ranges of temperature and salinity for individual water mass are integrated. Seasonal variations and formation mechanisms of water masses are briefly analyzed.

This work investigated the removal of cadmium ions (Cd2+) by using biochar derived from Barracuda Grass. The biochars derived from the pyrolysis of roots (BGR), stems (BGS) and leaves (BGL) were characterized and their performance for cadmium adsorption was studied at varying parameters of temperature, time, and alkali (earth) metal concentrations. The maximum adsorption amount at equilibrium of BGR, BGS and BGL was determined experimentally as 8.38 mg/g, 42.12 mg/g, and 30.39 mg/g. Adsorption fitting results revealed that Cd2+ adsorbed on BGR and BGS preferred to be multilayer-covered, and BGL was more likely to have monolayer-covered functions. The kinetic data fitted well to the pseudo-second-order model (R2 > 0.99), revealing the adsorption process was a spontaneous monolayer chemisorption process. The results of alkaline (earth) metals leaching of biochar revealed that the inherent alkaline (earth) metals in biochar made inhibitory functions on the Cd2+ adsorption behavior by occupying the active sites. And in the process of wastewater treatment, the leaching of alkaline earth metals might enhance the complexation reaction between surface groups and Cd2+. This study provides a feasible strategy for the resource utilization of abundant hydrophytic plants in waste management.

BackgroundGlucocorticoid-induced osteoporosis (GIOP) is a common form of secondary osteoporosis caused by the protracted or a large dosage of glucocorticoids (GCs). Total flavonoids of Drynariae rhizoma (TFDR) have been widely used in treating postmenopausal osteoporosis (POP). However, their therapeutic effects and potential mechanism against GIOP have not been fully elucidated.MethodsUltra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESIQ-TOF-MS) experiments were performed for qualitative analysis. We performed hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis to detect the changes in bone microstructure. The changes in biochemical parameters in the serum samples were determined by performing an enzyme-linked immunosorbent assay (ELISA). The prediction results of network pharmacology were verified via quantitative real-time polymerase chain reaction (qRT-PCR) to elucidate the potential mechanism of TFDR against GIOP.ResultsA total of 191 ingredients were identified in vitro and 48 ingredients in vivo. In the in-vivo experiment, the levels of the serum total cholesterol (TC), the serum triglyceride (TG), Leptin (LEP), osteocalcin (OC), osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRACP) and type-I collagen carboxy-terminal peptide (CTX-1) in the TFDR group significantly changed compared with those in the GIOP group. Moreover, the TFDR group showed an improvement in bone mineral density and bone microstructure. Based on the results of network pharmacology analysis, 67 core targets were selected to construct the network and perform PPI analysis as well as biological enrichment analysis. Five of the targets with high “degree value” had differential gene expression between groups using qRT-PCR.ConclusionTFDR, which may play a crucial role between adipose metabolism and bone metabolism, may be a novel remedy for the prevention and clinical treatment of GIOP.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations and the pathogenesis of SLE is still unclear. Various omics results have been reported for SLE, but the molecular hallmarks of SLE, especially in patients with different disease activity, using an integrated multi-omics approach have not been fully investigated. Here, we collected blood samples from 10 healthy controls (HCs) and 40 SLE patients with different clinical activity including inactive (IA), low activity (LA), and high activity (HA). Using an integrative analysis of proteomic, metabolomic and lipidomic profiles, we report the multi-omics landscape for SLE. The molecular changes suggest that both the complement system and the inflammatory response were activated in SLEs and were associated with disease activity. Additionally, activation of the immunoglobulin mediated immune response were observed in the LA stage of the disease, however this immune response was suppressed slightly in the HA stage. Finally, an imbalance in lipid metabolism, especially in sphingolipid metabolism, accompanied with dysregulated apolipoproteins were observed to contribute to the disease activity of SLE. The multi-omics data presented in this study and the characterization of peripheral blood from SLE patients may thus help provide important clues regarding the pathogenesis of SLE.

PurposeThe combination of irinotecan, temozolomide and vincristine has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination for patients with relapsed and refractory neuroblastoma (NB).Patients and MethodsIn this retrospective study, forty-six patients with relapsed or refractory NB were treated with the combination of vincristine (1.5 mg/m2 i.v. day 1), irinotecan (50 mg/m2/day i.v. days 1–5) and temozolomide (100 mg/m2/day p.o. days 1–5) (VIT) during the period 2011–2019. All toxicities were documented.ResultsA total of 251 cycles (median 6 cycles/patient) were administered. A complete response (CR) was achieved in 5 patients, partial response (PR) in 27 patients, stable disease (SD) in 8 patients, and progression disease (PD) in 6 patients, with an overall objective response rate (CR+PR) of 69.6%. Eighteen patients developed diarrhea with Grade 3 or less. Grade 1-2 hematologic toxicity occurred in 10 patients. Grade 3-4 hematologic toxicity developed in 32 patients. VIT was an effective regimen for different metastatic sites. UGT1A*28 genotyping performed in 7 patients revealed wild type. Diarrhea occurred in 4 of them.ConclusionThe shorter, 5-day VIT regimen is an active and well-tolerated salvage regimen in relapse/refractory NB.

Objective: Refractory or recurrent pediatric solid tumors lack effective treatments, and are associated with dismal outcomes. Hence, there is an urgent need for a novel therapeutic strategy. This study aimed to evaluate the efficacy and safety of anlotinib, a novel oral multi-kinase angiogenesis inhibitor, in pediatric patients with refractory or recurrent solid tumors.Methods: This single-institutional, observational retrospective study was conducted in Sun Yat-sen University Cancer Center, China. Refractory or recurrent pediatric solid tumor patients treated with anlotinib between 2018 and 2020 were evaluated.Results: Forty-one and 30 patients were enrolled to evaluate the efficacy and safety of anlotinib, respectively. There was partial response in five patients, stable disease in 22 patients, no patient with complete response, with an objective response ratio of 12.2% (5/41; 95% CI 1.7-22.7). The disease control rate was 65.9% (27/41; 95% CI 50.7-81) and the median progression-free survival was 2.87 months (95% CI 0.86-4.88). The incidence rates of any grade and grade 3–4 adverse events were 80% (24/30) and 23.3% (7/30), respectively. Bleeding (20%, 6/30), hand-foot syndrome (16.7%, 5/30), and diarrhea (13.3%, 4/30) were the most common adverse events. Grade 3–4 adverse events included hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There were no adverse events-related deaths.Conclusion: For heavily pretreated pediatric solid tumors, anlotinib monotherapy and its combination with chemotherapy may be an effective treatment option with tolerable adverse events. It is necessary to monitor blood pressure when using anlotinib in children.

Antigen-specific TRM persist and protect against skin or female reproductive tract (FRT) HSV infection. As the pathogenesis of HSV differs between humans and model organisms, we focus on humans with well-characterized recurrent genital HSV-2 infection. Human CD8+ TRM persisting at sites of healed human HSV-2 lesions have an activated phenotype but it is unclear if TRM can be cultivated in vitro. We recovered HSV-specific TRM from genital skin and ectocervix biopsies, obtained after recovery from recurrent genital HSV-2, using ex vivo activation by viral antigen. Up to several percent of local T cells were HSV-reactive ex vivo. CD4 and CD8 T cell lines were up to 50% HSV-2-specific after sorting-based enrichment. CD8 TRM displayed HLA-restricted reactivity to specific HSV-2 peptides with high functional avidities. Reactivity to defined peptides persisted locally over several month and was quite subject-specific. CD4 TRM derived from biopsies, and from an extended set of cervical cytobrush specimens, also recognized diverse HSV-2 antigens and peptides. Overall we found that HSV-2-specific TRM are abundant in the FRT between episodes of recurrent genital herpes and maintain competency for expansion. Mucosal sites are accessible for clinical monitoring during immune interventions such as therapeutic vaccination.

The strong stability of Cu–ethylenediaminetetraacetic acid (Cu–EDTA) results in the low decomplexation efficiency by the traditional Fenton process. For breaking this limitation, a three-dimensional electro-Fenton (3D-EF) system was constructed to study the decomplexation of Cu–EDTA at different pH, and the effects of Fe2+ concentration, particle electrode dosage, current density, and coexisting ions on decomplexation performance were investigated. The results showed that 3D-EF exhibited high pollutant removal efficiency in a wide pH range compared with the traditional electro-Fenton process. The optimal conditions for the removal of Cu–EDTA were as follows: the pH was 7, Fe2+ was 1 mmol L−1, granular activated carbon was 2 g L−1, and current density was 10 mA cm−2, and the optimum Cu–EDTA removal efficiency reached 90.95%. In addition, the presence of Cl− slightly improved the decomplexation efficiency, whereas NO3− and HPO42− inhibited the removal of Cu–EDTA. The kinetics of Cu–EDTA decomplexation in all experimental groups followed the first-order kinetic equation.

Background: Primary pulmonary hypertension (PPH) is a life-threatening disease associated with increased mortality. The urea cycle pathway plays a major role in PPH severity and treatment response. Little is known about the association of the blood urea nitrogen (BUN) and PPH prognosis.Methods: Clinical data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Adult patients (≥18 years) patients with primary pulmonary hypertension (PPH) in the database were enrolled. Spearman correlation was used to analyze the association of BUN with length of hospital and intensive care unit (ICU) stays. The chi-square test was used to analyze the association of BUN with mortality rate. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariable logistic regression was used to identify the BUN as an independent prognostic factor of mortality. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the sensitivity and specificity for mortality.Results: In total, 263 patients who met the selection criteria were enrolled. BUN was significantly positively associated with length of hospital stay and ICU stay (hospital stay: ρ = 0.282, ICU stay: ρ = 0.276; all P < 0.001). Higher hospital, 90-day and 4-year mortality rates were observed in the higher BUN quartile of PPH patients (hospital: P = 0.002; 90-day: P = 0.025; 4-year: P < 0.001). The Kaplan-Meier survival curves showed that patients in higher BUN quartile tended to have lower 4-year survival (Q1:7.65%, Q2: 10.71%; Q3: 14.80%, Q4: 16.84%; P < 0.0001). Logistic regression analyses found a significant association of BUN and mortality (hospital: OR = 1.05, 95% CI = 1.02–1.08, P = 0.001; 90-day: OR = 1.02, 95% CI = 1.00–1.05, P = 0.027; 4-year: OR = 1.05, 95% CI = 1.02–1.08, P = 0.001). Results of ROC and AUC showed that the diagnostic performance of BUN for mortality was moderately good.Conclusion: BUN was positively correlated with the length of hospital stay and ICU stay of PPH patients. Higher BUN was associated with higher hospital, 90-day and 4-year mortality and lower 4-year survival of PPH patients. These findings indicate that BUN can be a novel potential prognostic predictor for PPH.

Tissue-resident-memory T cells (TRM) populate the body’s barrier surfaces, functioning as frontline responders against reencountered pathogens. Understanding of the mechanisms by which CD8TRM achieve effective immune protection remains incomplete in a naturally recurring human disease. Using laser capture microdissection and transcriptional profiling, we investigate the impact of CD8TRM on the tissue microenvironment in skin biopsies sequentially obtained from a clinical cohort of diverse disease expression during herpes simplex virus 2 (HSV-2) reactivation. Epithelial cells neighboring CD8TRM display elevated and widespread innate and cell-intrinsic antiviral signature expression, largely related to IFNG expression. Detailed evaluation via T-cell receptor reconstruction confirms that CD8TRM recognize viral-infected cells at the specific HSV-2 peptide/HLA level. The hierarchical pattern of core IFN-γ signature expression is well-conserved in normal human skin across various anatomic sites, while elevation of IFI16, TRIM 22, IFITM2, IFITM3, MX1, MX2, STAT1, IRF7, ISG15, IFI44, CXCL10 and CCL5 expression is associated with HSV-2-affected asymptomatic tissue. In primary human cells, IFN-γ pretreatment reduces gene transcription at the immediate-early stage of virus lifecycle, enhances IFI16 restriction of wild-type HSV-2 replication and renders favorable kinetics for host protection. Thus, the adaptive immune response through antigen-specific recognition instructs innate and cell-intrinsic antiviral machinery to control herpes reactivation, a reversal of the canonical thinking of innate activating adaptive immunity in primary infection. Communication from CD8TRM to surrounding epithelial cells to activate broad innate resistance might be critical in restraining various viral diseases.

PurposeThe prognosis of relapsed or refractory pediatric Wilms tumor (WT) is dismal, and new salvage therapies are needed. This study aimed to evaluate the efficacy of the combination of irinotecan and a doxorubicin hydrochloride liposome regimen for relapsed or refractory pediatric WT.Patients and MethodsThe present study enrolled relapsed or refractory pediatric WT patients who were treated with the AI regimen (doxorubicin hydrochloride liposomes 40 mg/m2 per day, day 1, and irinotecan 50 mg/m2 per day with 90-min infusion, days 1–5; this regimen was repeated every 3 weeks) at Sun Yat-sen University Cancer Center from July 2018 to September 2020. The response was defined as the best-observed response after at least two cycles according to the Response Evaluation Criteria of Solid Tumors (RECIST 1.1), and toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03).ResultsA total of 16 patients (male:female, 8:8) with a median age of 4.2 years (0.5–11 years) with relapsed or refractory disease were enrolled in this study, including 14 patients with relapsed disease and two patients with refractory disease. These patients received 1–8 courses (median, 3 courses) of the AI regimen. Fourteen patients were assessable for response: two with complete response (CR), five with partial response (PR), two with stable disease (SD), and five with progressive disease (PD). The objective response rate was 50% (two CR, five PR), and the disease control rate was 64% (two CR, five PR, and two SD). Seven out of 14 patients (50%) were alive at the last follow-up, ranging from 2.6 to 32.4 months. The median progression-free survival and median overall survival were 3.5 months (range 0.5–12 months) and 8 months (range 1–28 months), respectively. Sixteen patients were assessable for toxicity, with the most common grade 3 or 4 adverse events being alopecia (62%), leukopenia (40%), abdominal pain (38%), diarrhea (23%), and mucositis (16%), etc. No fatal adverse events have been observed, and modest adverse effects can be administered.ConclusionIrinotecan and doxorubicin hydrochloride liposome regimens have positive efficacy on relapsed or refractory pediatric WT with well-tolerated toxicity. A prospective clinical trial is warranted.

Ovarian cancer, a common malignant tumor, is one of the primary causes of cancer-related deaths in women. Systemic chemotherapy with platinum-based compounds or taxanes is the first-line treatment for ovarian cancer. However, resistance to these chemotherapeutic drugs worsens the prognosis. The underlying mechanism of chemotherapeutic resistance in ovarian cancer remains unclear. Non-coding RNAs, including long non-coding RNAs, microRNAs, and circular RNAs, have been implicated in the development of drug resistance. Abnormally expressed non-coding RNAs can promote ovarian cancer resistance by inducing apoptosis inhibition, protective autophagy, abnormal tumor cell proliferation, epithelial-mesenchymal transition, abnormal glycolysis, drug efflux, and cancer cell stemness. This review summarizes the role of non-coding RNAs in the development of chemotherapeutic resistance in ovarian cancer, including their mechanisms, targets, and potential signaling pathways. This will facilitate the development of novel chemotherapeutic agents that can target these non-coding RNAs and improve ovarian cancer treatment.

There is limited experience of PD-1 antibody combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. This is a retrospective-case study conducted in two Chinese expert centers. The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities. Of the 22 pediatric patients with cancer who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0 - 43 months). PD-1 antibody monotherapy demonstrated antitumor activity in a population of pediatric patients with Hodgkin lymphoma (HL), with an objective response rate (ORR) and disease control rate (DCR) of 83.3% (3CR and 2PR) and 100%, respectively. However, no objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. We reviewed responses for patients with chemotherapy, decitabine or everolimus combination therapies with PD-1 antibodies, and found that PD-1 antibody combined with decitabine showed potential efficacy in pediatric patients with advanced embryonal rhabdomyosarcoma and lymphoepitheliomatoid-like carcinoma. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 antibody monotherapy in Asian pediatric patients with lower incidence of hematologic toxicity and nonhematologic toxicity. The Grade ≥3 TRAEs were attributed to the combination chemotherapy.

Background: Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury.Method: ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis.Results: Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and H2O2-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and H2O2-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and H2O2-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis.Conclusions: Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and H2O2-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways.

Background: Chinese medicine injection is wildly used in Acute Lung Injury and Acute respiratory distress syndrome (ALI/ARDS) treatment. However, what kinds of CMIs are more effective in the ALI/ARDS treatment is uncertain.Objectives: Compare the efficacy of different CMIs to identify the optimal one for the therapy of ALI/ARDS patients.Data sources: We searched the data up to April 30, 2020 from MEDLINE, EMBASE, The Cochrane Library, Web of Science, the China Science Journal Citation Report (VIP database), WanFang and the China National Knowledge InfrastructureStudy selection: Randomized Clinical Trials assessed at least one of the following outcomes: mortality, Oxygenation Index, length of ICU stay, mechanical ventilation duration, APACHEⅡ score, SOFA score and Murray score, for adult patients of ALI/ADRS. Eligible Studies should also use CMIs as complementary therapies in addition to the standard treatment.Data extraction and synthesis: Two reviewers independently assessed the data. Then, we used a Bayesian random-effects network meta-analysis for data synthesis.Results: Twenty-six studies were selected (involved 2073 participants). Seven kinds of CMIs were evaluated. Compared with standard treatment, Xuebijing is associated with lower mortality. Tanreqing and Xuebijing have the best effect on improving the Oxygenation Index. Huangqi, Danshen, Tanreqing and Xuebijing can significantly reduce the APACHE II score (Huangqi works better than Xuebijing). Huangqi and Xuebijing have the best effect on reducing mechanical ventilation duration and Murray score, while Xuebijing has the best effect on shortening the length of ICU stay.Conclusions: As adjuvant drugs, Xuebijing, Tanreqing and Huangqi show certain effects on treating ALI/ARDS in different aspects.

Important strides have been made toward understanding the relationship between self-efficacy and life satisfaction. However, existing studies have largely focused on work and academic domains, leaving self-efficacy in the finance domain less frequently investigated. The present study applied the self-efficacy construct to the finance domain, namely “financial self-efficacy” (FSE), and tested the sequential mediating roles of high standards tendency and investment satisfaction in the relationship between FSE and general life satisfaction. A total of 323 employees from finance-related businesses completed anonymous questionnaires regarding FSE, high standards tendency, investment satisfaction, and general life satisfaction. Results indicated that FSE influenced general life satisfaction through investment satisfaction, and sequentially through high standards tendency and investment satisfaction. These results provide contributions to the current literature on life satisfaction, and positive psychology literature by shedding light on the roles of high standards tendency and investment satisfaction in the relation between FSE and general life satisfaction.

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

ObjectiveThe aim of this study was to compare the accuracy of the Children’s Oncology Group (COG) risk stratification system to the Children’s Hepatic tumor International Collaboration (CHIC) risk stratification system for predicting the prognosis of Chinese children with hepatoblastoma (HB).MethodsClinicopathological data of 86 patients diagnosed with HB between January 2014 and December 2017 were retrieved. The study endpoints were the 1- and 3-year overall survival (OS) and disease-free survival (DFS) were analyzed to evaluate the predictive value.ResultsThe 1-, 3-year OS and DFS of the 86 patients were 86.0%, 76.3%, and 74.4%, 54.0%, respectively. Univariate analyses revealed that age at diagnosis had a significant role in prognosis for both OS and DFS, along with PRETEXT staging and metastasis at diagnosis. Multivariate analysis showed that metastasis at diagnosis (HR 3.628, 95% CI 1.404-9.378, P=0.008), PRETEXT staging system (HR 2.176, 95% CI 1.230-3.849, P=0.008) and age at diagnosis (HR 2.268, 95% CI 1.033-4.982, P=0.041) were independent factors for OS. For DFS, the independent factors were the PRETEXT staging system (HR 2.241, 95% CI 1.533-3.277, P

An efficient Fenton-like catalyst CuO/CeO2 was synthesized using ultrasonic impregnation and used to remove diclofenac from water. The catalyst was characterized by N2 adsorption-desorption, SEM-EDS, XRD, HRTEM, Raman, and XPS analyses. Results showed that CuO/CeO2 possessed large surface area, high porosity, and fine elements dispersion. Cu was loaded in CeO2, which increased the oxygen vacancies. The exposed crystal face of CeO2 (200) was beneficial to the catalytic activity. The diclofenac removal experiment showed that there was a synergistic effect between CuO and CeO2, which might be caused by more oxygen vacancies generation and electronic interactions between Cu and Ce species. The experimental conditions were optimized, including pH, catalyst and H2O2 dosages, and 86.62% diclofenac removal was achieved. Diclofenac oxidation by ·OH and adsorbed oxygen species was the main mechanism for its removal in this Fenton-like system.

The disposition effect refers to the tendency of investors to sell winners too early and hold on to losers too long, which is one of the most documented and robust decision biases. However, few studies have looked beyond demographic and social factors on the disposition effect. The current study investigated the association between financial self-efficacy (FSE) (one’s belief about their personal capability in ultimate financial goals achieving), versatile cognitive style (an individual’s capability in deploying the experiential or rational mode in ways that are contextually appropriate), and the disposition effect. A total of 285 employees from finance-related business completed anonymous questionnaires regarding FSE, rational-experiential inventory, and the disposition effect. Our findings revealed that FSE was significantly and positively associated with versatile cognitive style and the disposition effect. Further, versatile cognitive style partially mediated the relationship between FSE and the disposition effect. Our findings provide valuable guidance for individual investors to make financial decisions based on their characteristics.

A reward that is personally relevant tends to induce stronger pursuit motivation than a reward that is linked to other people. However, the role of attention in eliciting this “self-referential reward effect” remains unclear. In our two studies, we evaluated the significance of attention in self-referential reward processing utilizing an ownership paradigm, which required participants to complete a visual search task to win either monetary rewards (in Study 1) or social rewards (in Study 2) for themselves or for an acquaintance. Access to attentional resources was manipulated by sometimes including a distracting stimulus among the presented stimuli. The results of Study 1 revealed that a significant self-referential reward effect emerged under undistracted attentional conditions and was associated with improved task performance when self-owned monetary rewards were available. However, distracted attention impaired this self-referential reward effect. Moreover, distracted attention was also observed in the self-referential social reward processing in Study 2. These results suggested that distracted attention can impair the pursuit advantage for self-relevant rewards; self-referential processing is strongly dependent on attentional resources.

Understanding neuronal mechanisms of learned behaviors requires efficient behavioral assays. We designed a high-throughput automatic training system (HATS) for olfactory behaviors in head-fixed mice. The hardware and software were constructed to enable automatic training with minimal human intervention. The integrated system was composed of customized 3D-printing supporting components, an odor-delivery unit with fast response, Arduino based hardware-controlling and data-acquisition unit. Furthermore, the customized software was designed to enable automatic training in all training phases, including lick-teaching, shaping and learning. Using HATS, we trained mice to perform delayed non-match to sample (DNMS), delayed paired association (DPA), Go/No-go (GNG), and GNG reversal tasks. These tasks probed cognitive functions including sensory discrimination, working memory, decision making and cognitive flexibility. Mice reached stable levels of performance within several days in the tasks. HATS enabled an experimenter to train eight mice simultaneously, therefore greatly enhanced the experimental efficiency. Combined with causal perturbation and activity recording techniques, HATS can greatly facilitate our understanding of the neural-circuitry mechanisms underlying learned behaviors.

The characteristics and performances of catalyst are the key in catalytic ultrasonic treatment of wastewater, and iron based catalysts are known for low cost, high accessibility and safety. This paper reviewed the current research status of iron-based catalysts in water treatment assisted by ultrasound. Zero valent iron, Fe3O4 and iron composited with other metals were analyzed, their behaviors in catalytic sonochemistry were summarized, and the potential catalytic mechanisms were discussed in details. Finally, the future development in this field was proposed.

Photocatalytic degradation has been extensively investigated toward the removal emerging contaminants (ECs) from water. In this study, a series of Ag-Bi3O4Cl plasmon photocatalysts were synthesized through the photo-deposition of metallic Ag on the Bi3O4Cl surface. The effects of plasmon modification on the catalytic performance of bismuth oxychlorides were analyzed. Ag addition did not alter the morphology of Bi3O4Cl. With the increasing Ag content, the number of oxygen defects on the catalyst surface first increased and then decreased. Moreover, the surface plasmon resonance effect of Ag suppressed the recombination of electron-hole pairs, promoting the migration and separation of photocarriers and improving the light absorption efficiency. However, the addition of excessive Ag reduced the number of active sites on the Bi3O4Cl surface, hindering the catalytic degradation of pollutants. The optimal Ag-Bi3O4Cl photocatalyst (Ag ratio: 0.025; solution pH: 9; dosage: 0.8 g/L) achieved 93.8 and 94.9% removal of ciprofloxacin and tetrabromobisphenol A, respectively. The physicochemical and photoelectric properties of Ag-Bi3O4Cl were determined through various characterization techniques. This study demonstrates that introducing metallic Ag alters the electron transfer path of the catalyst, reduces the recombination rate of electron-hole pairs, and effectively improves the catalytic efficiency of Bi3O4Cl. Furthermore, the pathways of ciprofloxacin degradation products and their biotoxicity were revealed. [ABSTRACT FROM AUTHOR]

Members of the YABBY gene family play significant roles in lamina development in cotyledons, floral organs, and other lateral organs. The Orchidaceae family is one of the largest angiosperm groups. Some YABBYs have been reported in Orchidaceae. However, the function of YABBY genes in Cymbidium is currently unknown. In this study, 24 YABBY genes were identified in Cymbidium ensifolium, C. goeringii, and C. sinense. We analyzed the conserved domains and motifs, the phylogenetic relationships, chromosome distribution, collinear correlation, and cis-elements of these three species. We also analyzed expression patterns of C. ensifolium and C. goeringii. Phylogenetic relationships analysis indicated that 24 YABBY genes were clustered in four groups, INO, CRC/DL, YAB2, and YAB3/FIL. For most YABBY genes, the zinc finger domain was located near the N-terminus and the helix-loop-helix domain (YABBY domain) near the C-terminus. Chromosomal location analysis results suggested that only C. goeringii YABBY has tandem repeat genes. Almost all the YABBY genes displayed corresponding one-to-one relationships in the syntenic relationships analysis. Cis-elements analysis indicated that most elements were clustered in light-responsive elements, followed by MeJA-responsive elements. Expression patterns showed that YAB2 genes have high expression in floral organs. RT-qPCR analysis showed high expression of CeYAB3 in lip, petal, and in the gynostemium. CeCRC and CeYAB2.2 were highly expressed in gynostemium. These findings provide valuable information of YABBY genes in Cymbidium species and the function in Orchidaceae. [ABSTRACT FROM AUTHOR]

Introduction: Diarrhea-predominant irritable bowel syndrome (IBS-D) significantly decreases the quality of life of patients and their families, and affects patients' mental health. No specific western medications are available. Ancient classical Chinese medical texts have recognized Tongxie Yaofang (TXYF) as a therapy for diarrhea which is widely used in clinical practice. Standard TXYF prescription (S-TXYF) is composed of four herbal medicines: Atractylodes macrocephala Koidz. [Asteraceae; Rhizoma Atractylodis Macrocephalae.], Paeonia lactiflora Pall. [Ranunculaceae; Paeoniae Radix Alba], Citrus × aurantium L. [Rutaceae; Citri Reticulatae Pericarpium] and Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk. [Umbelliferae; Saposhnikoviae Radix]. This review aimed to evaluate the therapeutic effects and safety of S-TXYF for IBS-D. Methods: Eight English and Chinese electronic databases were searched from their inception to 25 December 2021 for randomized controlled trials (RCTs) comparing S-TXYF with placebo, western medications or no treatment for IBSD. The primary outcome was the global improvement of IBS-D symptoms. Data were analyzed using Cochrane's Revman 5.4 software. Evidence certainty was assessed using the online GRADEpro tool for the primary outcome. Results: Eleven RCTs involving 985 adults with IBS-D were included. For global improvement of symptoms, S-TXYF was superior to western medication and placebo (moderate evidence by GRADE). Regarding the improvement of stool consistency, stool frequency and abdominal pain, S-TXYF was significantly effective than placebo. In addition, S-TXYF was superior to western medication on improving the quality of life and relieving anxiety. Six trials reported adverse events: five of them reported (non-serious) adverse events occurred in both groups, and one trial reported that 3 cases with adverse events (constipation, elevation in liver-enzyme, nausea) occurred in S-TXYF group and 3 cases with adverse events (abdominal distension, nausea) occurred in placebo group. Conclusion: Although current results showed that S-TXYF may have potential to treat IBS-D and its use appears to be safe, no a clear and confirmed conclusion can be drawn from our review as the overall inadequate design of the included trials reviewed. So more rigorous trials are warranted to establish confirmed evidence on its benefits and safety. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a non-scarring hair loss disorder. Alopecia totalis (AT) and alopecia universalis (AU) are the severe subtypes of AA. Age of onset before 6 years of age, disease duration of more than 1 year, and extensive alopecia involving more than 50% of the scalp (including AT or AU) suggest a poorer prognosis. Topical corticosteroids are the preferred first-line treatment for pediatric AA. While some treatments, such as intralesional corticosteroids, systemic steroids, contact immunotherapy with squaric acid dibutyl ester, and JAK inhibitors, showed efficacy in adults with AA, their safety profiles limit their use in pediatric AA patients. Dupilumab is a biologic that effectively addresses the patho-physiology of Th2 allergic diseases, and treats atopic diseases by inhibiting the helper Th2 immune axis. AA has been reported to be significantly improved with dupilumab for atopic dermatitis (AD) in children and adults. We report hair regrowth over all of the scalp, eyebrows, and eyelashes after 10 months of dupilumab therapy in a 4-year-old AU patient resistant to baricitinib.

As low environmental temperature adversely affects the growth, development and geographical distribution, plants have evolved multiple mechanisms involving changing physiological and metabolic processes to adapt to cold stress. In this study, we revealed that nucleoporin-coding gene OsSEH1 was a positive regulator of cold stress in rice. Physiological assays showed that the activity of antioxidant enzymes showed a significant difference between osseh1 knock-out lines and wild type under cold stress. Metabolome analysis revealed that the contents of large-scale flavonoids serving as ROS scavengers were lower in osseh1 mutants compared with wild type under cold stress. Transcriptome analysis indicated that the DEGs between osseh1 knock-out lines and wild type plants were enriched in defense response, regulation of hormone levels and oxidation-reduction process. Integration of transcriptomic and metabolic profiling revealed that OsSEH1 plays a role in the oxidation-reduction process by coordinately regulating genes expression and metabolite accumulation involved in phenylpropanoid and flavonoid biosynthetic pathway. In addition, Exogenous ABA application assays indicated that osseh1 lines had hypersensitive phenotypes compared with wild type plants, suggesting that OsSEH1 may mediate cold tolerance by regulating ABA levels.

Hemophagocytic lymphohistiocytosis (HLH) can be classified into primary HLH and secondary HLH. Primary HLH usually occurs in infants and children with an underlying genetic defect, and there are also teens and occasional adults with primary HLH. Most cases with secondary HLH are adult patients with secondary triggers including infections, malignancies, and autoimmune diseases. The distinction between primary HLH and secondary HLH seems to be less straightforward, as patients with secondary HLH may also have genetic defects while primary HLH can be triggered by secondary causes. In this study, using amplicon-based targeted gene sequencing (TGS), we sequenced eighteen HLH-related genes in 112 adult HLH cases, which were mostly secondary HLH. Mutations or rare variants were identified in 48 cases (42.9%). All the variants except one were missense variants, and biallelic gene mutations were identified in 3 cases in which only one case harbored homogenous missense mutation. Recurrent variants including UNC13D p.G863D and AP3B1 p.T359A are much more prevalent in our cohort than in normal East Asian population, and in silico analysis predicted pathogenicity of these variants. In conclusion, according to our study, genetic defects may also contribute to the development of adult HLH cases or secondary HLH cases. [ABSTRACT FROM AUTHOR]

PurposeAbnormal placentation is a spectrum disorder that includes creta, increta, and percreta; the term placenta accreta spectrum (PAS) disorders is used as a broad term to describe all of these conditions. PAS can lead to life-threatening hemorrhage. The predictive value of cervical length (CL) in patients with PAS remains controversial. Thus, this study investigated the relationship between CL and the probability of major bleeding in patients with PAS and placenta previa.MethodsThis retrospective cohort study was conducted at a comprehensive tertiary hospital in Chongqing, China, between January 2018 and December 2020. The target independent and dependent variables were CL and intraoperative massive bleeding, respectively. The covariates included demographic, clinical, and ultrasound characteristics. Logistic regression was used to explore the association between CL and massive bleeding.ResultsIn total, 317 participants were enrolled, in whom the prevalence of massive bleeding was 41.9% (133/317). The threshold of CL associated with massive bleeding (≥1,000 ml) was 33 mm based on a receiver operating characteristic curve. In the fully adjusted model for each additional unit of CL, the risk of massive bleeding decreased by 7% [95% confidence interval (CI), 0.88–0.98]. The risk of major bleeding was reduced by 44% in patients with a CL greater than 33 mm (95% CI, 0.33–0.97) compared with patients with a CL less than 33 mm.ConclusionsCL was negatively associated with massive intraoperative bleeding in patients with PAS combined with placenta previa. When the CL was greater than 33 mm, the risk of bleeding decreased by 44%. Thus, CL can be used as a standalone parameter to identify the risk of massive intraoperative bleeding in patients with suspected PAS.

Background and objective:Andrographis paniculata (AP) is a traditionally used herbaceous plant, whose main active constituent is andrographolide. Andrographolide derivative medications and herbal preparations of AP are often used to treat respiratory tract infections. This study aims to systematically evaluate the safety of andrographolide derivative medications and herbal preparations of AP based on clinical studies.Methods: English and Chinese databases were searched for all types of clinical studies that reported adverse drug reactions (ADRs) and adverse events (AEs) of andrographolide derivative medications and herbal preparations of AP. The ADRs and AEs were classified according to manifestations, and graded according to severity. Single-rate meta-analysis was performed for ADR incidence using R software.Results: A total of 262 studies were included, including 125 randomized controlled trials, 23 non-randomized controlled trials, 6 case series, and 108 case reports. In 9490 participants using andrographolide derivative injections, 383 (4.04%) reported ADRs. Meta-analysis showed that the ADR incidence of three most frequently used injections of andrographolide derivatives (andrographolide sulfonate, potassium sodium dehydroandrographolide succinate, and potassium dehydroandrographolide succinate) were 5.48% [95% CI (4.47%, 6.72%)], 3.69% [95% CI (2.59%, 4.94%)] and 5.33% [95% CI (3.68%, 7.72%)], respectively, which may be slightly higher than the actual ADR incidence, because only studies that reported the occurrence of ADRs or AEs were included, but studies without ADR and AE were not included. The ADRs of andrographolide derivative injections were mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Fifty-five patients experienced life-threatening anaphylactic shock, three patients died, and the causation attributed to the andrographolide derivative injection. Other ADRs were mild, moderate or medically significant. Nine herbal preparations of AP were tested in 10 studies, and the reported ADRs were mainly mild to moderate gastrointestinal, skin and subcutaneous tissue disorders. Except for five patients using andrographolide derivative injections eventually died, most of the ADRs were alleviated after drug withdrawal and symptomatic treatment.Conclusions: The ADRs of andrographolide derivative medications are few, but can be life-threatening, mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Injections of andrographolide derivatives should be used with caution. Herbal preparations of AP are essentially safe.Systematic Review Registration: [website], identifier [registration number]

Background and objective: Cancer is a life-threatening disease worldwide and current standard therapy cannot fulfill all clinical needs. Chinese herbal injections have been widely used for cancer in Chinese and Western hospitals in China. This study aimed to apply evidence mapping in order to provide an overview of the clinical application of Chinese herbal injections in cancer care based on randomized controlled trials, systematic reviews, and meta-analyses.Methods and results: Seven databases were systematically searched for eligible randomized controlled trials, systematic reviews, and meta-analyses for ten Chinese herbal injections used in cancer treatment and covered in the Chinese national essential health insurance program. Excel 2016 and RStudio were used to integrate and process the data.In total 366 randomized controlled trials and 48 systematic reviews and meta-analyses were included in the evidence mapping of herbal medicines including; Compound Kushen, Shenqi Fuzheng, Aidi, Kangai, Kanglaite, Xiaoaiping, Cinobufacin, Brucea javanica oil emulsion, Polyporus polysaccharide injection, and Astragalus polysaccharide for injection. Health insurance restricts the scope of clinical application for these herbal injections. The numbers of studies published increased, especially around 2013–2015. The most studied cancer types were lung cancer (118, 32.2%), colorectal cancer (39, 10.7%), and gastric cancer (39, 10.7%), and the most used injections were Compound Kushen (78, 21.3%), Shenqi Fuzheng (76, 20.8%), and Aidi (63, 17.2%). The most consistently reported benefits were observed for Compound Kushen, Shenqi Fuzheng, Aidi, and Kangai for tumor response, quality of life, myelosuppression, and enhancing immunity.Conclusion: The current evidence mapping provides an overview of the outcomes and effects of Chinese herbal injections used in cancer care, and offers information on their clinical application which warrants further evidence-based research in order to inform clinical and policy decision-making.

Background: Hemodialysis patients not only suffer from somatic disorders but are also at high risks of psychiatric problems. Early this year, the outbreak of coronavirus disease 2019 (COVID-19) has caused great panic and anxiety worldwide. The impact of this acute public health event on the psychological status of hemodialysis patients and its relationship with their quality of life have not been fully investigated.Methods: This study comprised two parts. The initial study enrolled maintenance hemodialysis patients treated in Ruijin Hospital for more than 3 months from March to May 2020 during the ongoing COVID-19 pandemic. Patients completed three questionnaires including the Impact of Events Scale–Revised (IES-R), General Health Questionnaire-28 (GHQ-28), and Kidney Disease Quality of Life (KDQOL) Short Form (SF). Follow-up study was performed from December 2020 to January 2021, when the pandemic of COVID-19 has been effectively contained in China. Only patients enrolled in the initial study were approached to participate in the follow-up study.Results: There were 273 maintenance dialysis patients enrolled in the initial study and 247 finished the follow-up study. For the initial study, the estimated prevalence of nonspecific psychiatric morbidity was 45.8% (125/273) by GHQ-28. By IES-R, 53/273 (19.4%) patients presented with total scores above 24 that reflected clinical concerns. We found a significant difference regarding KDQOL scores between patients with different stress response (IES-R) groups (p = 0.026). Our follow-up study showed that KDQOL and SF-36 scores were significantly improved in comparison with those in the initial study (p = 0.006 and p = 0.031, respectively). Though total scores of GHQ-28 and IES-R did not change significantly, some subscales improved with statistical significance. Furthermore, gender, education background, and duration of hemodialysis were three factors that may affect patients' mental health, quality of life, or health status while dialysis duration was the only variable that correlated with those parameters. However, these correlations were combined effects of the COVID-19 pandemic and the dialysis itself.Conclusions: We found a correlation between changes in the mental health status of dialysis patients and changes in their quality of life. These responses were also mediated by patients' psychosocial parameters. Our results urge the necessity of psychotherapeutic interventions for some patients during this event.

Purpose: To investigate the predictive values of plasma Epstein-Barr Virus (EBV)- deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC).Patients and Methods: Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre- and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival.Results: A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment (N = 66), post-treatment (N = 93) and/or during follow-up (N = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ≤ 10,000 copies/mL, 37.2 vs. 75.1%, p = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, p < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52–7.78; p = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8–99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ≤ 1,000 copies/mL, 72.9 vs. 100%, p < 0.001).Conclusions: Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.

Objective: To investigate the correlation between periodontal disease and breast cancer.Materials and Methods: PubMed and China National Knowledge Infrastructure (CNKI) databases were searched up to February 8, 2018 for observational studies examining the association between periodontal disease and breast cancer. Study selection was conducted according to predesigned eligibility criteria, and two authors independently extracted data from included studies. Meta-analysis was performed using the Comprehensive Meta-Analysis v2 software and risk estimates were calculated as relative risks (RRs) with corresponding 95% confidence intervals (CIs).Results: A total of 11 study were included. Meta-analysis indicated that periodontal disease significantly increased the risk of breast cancer by 1.22-fold (RR = 1.22, 95% CI = 1.06–1.40). Amongst participants with periodontal patients and a history of periodontal therapy, the risk of developing breast cancer was not significant (RR = 1.23; 95% CI = 0.95–1.60). The association results between periodontal diseases and breast cancer were found to be robust, as evident in the leave-one-out sensitivity analysis.Conclusions: Periodontal disease may be a potential risk factor for the development of breast cancer among women, and thus effective periodontal therapy may present as a valuable preventive measure against breast cancer.