In the context of global climate change, the impact of ambient temperature change on cardiovascular health has become increasingly significant. Epidemiological studies have shown that both high and low temperature can lead to the occurrence of adverse cardiovascular outcomes. For example, exposure to low temperature and high temperature, and diurnal temperature difference can increase the risk of cardiovascular diseases (CVD) mortality. Exposure to cold and heat, heatwaves and cold spells may induce myocardial infarction. Low temperature, high temperature and variations in temperature can increase the risk of heart failure. There are complex interactions among the effects of temperature and humidity, wind speed, radiation, precipitation and air pollution on adverse cardiovascular outcomes. Valnerable groups such as the elderly, patients with chronic diseases, and outdoor workers are particularly susceptible to temperature-related CVD risks. The mechanisms by which temperature affects adverse cardiovascular outcomes involves hemodynamic changes, autonomic nervous system dysregulation, blood rheology alterations, as well as inflammation and metabolic abnormalities, but many research gaps remain. Future studies should conduct in-depth research on mechanisms, individual differences, climate change impacts, and public health interventions to provide more effective policies and interventions to reduce the burden of CVD.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have emerged as critical agents for cancer therapy. By inhibiting the catalytic activity of PARP enzymes and trapping them in the DNA, PARPis disrupt DNA repair, ultimately leading to cell death, particularly in cancer cells with homologous recombination repair deficiencies, such as those harboring BRCA mutations. This review delves into the mechanisms of action of PARPis in anticancer treatments, including the inhibition of DNA repair, synthetic lethality, and replication stress. Furthermore, the clinical applications of PARPis in various cancers and their adverse effects as well as their combinations with other therapies and the mechanisms underlying resistance are summarized. This review provides comprehensive insights into the role and mechanisms of PARP and PARPis in DNA repair, with a particular focus on the potential of PARPi-based therapies in precision medicine for cancer treatment.
Humans ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Neoplasms/genetics* ; DNA Repair/drug effects* ; Animals ; Antineoplastic Agents/therapeutic use*

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

【Objective】 To explore the effects of breastfeeding on the immune response of CD4⁺T lymphocytes in infants in non-inflammatory state, and to analyze the immunomodulatory significance of the whole composition of breast milk. 【Methods】 A retrospective cohort study was conducted. From January to September 2022, six-month-old infants who took physical examination in the Child Healthcare Department of Changzhou Children′s Hospital Affiliated to Nantong University, were selected based on inclusion criteria, and were divided into breastfeeding group (n=33) and formula feeding group (n=27) based on their feeding patterns. Flow cytometry was used to detect the percentage of CD4⁺ T cells, including helper T cell (Th) 1, Th2, Th17, regulatory T cell (Treg), and the levels of related cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17 in peripheral blood. The differences in these indicators between the two groups were compared. 【Results】 Compared with the formula feeding group, the breastfeeding group showed significantly higher percentages of Th1(t=3.038), Treg (t=2.088). The ratio of Th1 to Th2(Z=2.756), IL-10(Z=2.297) and IFN-γ (Z=2.076) in the peripheral blood of the breastfeeding group were also significantly higher. Conversely, the breastfeeding group had significantly lower percentage of Th17(Z=2.704) and IL-17A (t=2.187) (P<0.05). There was no significant difference the percentage of Th2, as well as in the levels of IL-2, IL-4, IL-6 and TNF-α between the two groups (P>0.05). 【Conclusions】 Breastfeeding has a regulatory effect on the immune response of infant CD4⁺ T lymphocytes. It promotes the development of Th1/Th2 towards Th1 and the immunomodulatory effect of Treg. Moreover, it inhibits the Th17 type immune response. These findings suggest that the complete composition of breast milk contributes to the development and maturation of infant immune system, enhancing immune defense and immune tolerance.

This article provides an interpretive review of the "2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation", which was updated and published by the American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) based on the latest clinical evidence. It delves into the classification and management strategies for atrial fibrillation (AF), grounded in the most current evidence-based medical research. The guideline offers significant updates in various aspects such as the definition and staging of AF, clinical evaluation and treatment, modification of risk factors, prevention of thromboembolism, and management of specific populations. Notably, the introduction of a new staging model for AF and corresponding management strategies stands out, underscoring the importance of prevention and early intervention. This article focuses on the three pillars of integrated AF management—stroke risk assessment, modification of risk factors, and management of specific patient groups, in addition to rate and rhythm control, analyzes their substantial significance in clinical practice and guides clinicians in providing more precise treatment.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

Objective To explore the role of clinical pharmacists involved in the case of a patient with acute myeloid leukemia whose QTc interval prolongation was induced by gilteritinib,and to provide reference for drug treatment and monitoring of those patients.Methods The abnormal electrocardiogram(ECG)of a patient with acute myeloid leukemia was found in time by clinical pharmacists,who participated in clinical diagnosis and treatment by analyzing the patient's underlying diseases,diagnosis and treatment process,therapeutic drugs and their potential interactions.Results Clinical pharmacists suspected that the prolonged QTc interval was likely to be an adverse reaction caused by gilteritinib,and recommended immediate discontinuation of the drug and re-examination of the electrocardiogram.The physician took the suggestion to stop the suspected drug therapy with gilteritinib promptly,and ECG was rechecked 3 d later,and the QTc value returned to the normal range.Conclusion Clinical pharmacists participating in clinical diagnosis and treatment could provide better pharmaceutical care for patients.

Objective To observe the values of changes of right heart modified myocardial performance index(Mod-MPI)and ductus venosus(DV)spectrum parameters in pre-eclampsia fetuses for predicting adverse pregnancy outcomes.Methods Eighty-one pregnant women diagnosed as pre-eclampsia were prospectively enrolled and divided into severe pre-eclampsia(SPE)group(n=39)and mild pre-eclampsia(MPE)group(n=42),while 85 healthy pregnant women were taken as controls(control group).Fetal right heart function parameters,including right ventricular isovolumetric relaxation time(IRT),isovolumetric contraction time(ICT),ejection time(ET),total spent time(TST),Mod-MPI,tricuspid valve peak flow velocity ratio in early and late diastole(TV-E/A),as well as blood flow velocities in each waveform of DV spectrum(S,V,D,and A wave)were obtained,and the pulsatility index(PI)and the ratio of blood flow velocities in each waveform of the DV(S/V,S/D,S/A,V/D,V/A,D/A)were calculated.Intrauterine fetal distress,preterm delivery,neonatal asphyxia and newborn with low weight were considered as adverse pregnancy outcomes.The correlations of right heart Mod-MPI and TV-E/A with DV parameters in pre-eclampsia fetuses were assessed,and their predictive efficacies for adverse pregnancy outcomes were evaluated for right heart Mod-MPI and DV using the receiver operating characteristics(ROC)and the area under the curves(AUC).Results Compared with control group and MPE group,fetal right heart IRT,ICT and Mod-MPI increased and ET decreased in SPE group(all P＜0.05).No significant differences of right heart TST and TV-E/A among 3 groups(both P＞0.05).Fetal DV A-wave velocity and V/D values progressively decreased but PI progressively increased in control,MPE and SPE groups(all P＜0.05).Fetal right heart Mod-MPI in pre-eclampsia was moderately positively correlated with DV PI(r=0.637,P=0.016),while TV-E/A was weakly negatively correlated with DV V/D(r=-0.355,P=0.043).Adverse pregnancy outcomes were noticed in 59 pre-eclampsia cases.The AUC of fetal right heart Mod-MPI and DV PI for predicting adverse pregnancy outcomes in pre-eclampsia cases was 0.897 and 0.848,respectively,without significant difference(Z=0.460,P=0.400).Conclusion Changes of right heart Mod-MPI and DV spectrum parameters in pre-eclampsia fetuses had high value for predicting adverse pregnancy outcomes.

Abstract OBJECTIVE To develop LC-MS method for the simultaneous determination of impurities A, C, and D of caspofungin acetate. METHODS Waters CORTECS® C18+(4.6 mm×150 mm, 2.7 μm) was used as the chromatography column. Mobile phase A and B were 0.1% formic acid-H2O and 0.1% formic acid-CH3CN, respectively. Electrospray ion source-single quadrupole mass spectrometry was used to detect impurities A and C in positive ion mode and impurity D in negative ion mode. RESULTS The correlation coefficient r was ≥ 0.999 in linearity ranges of impurities A, C and D. The average recoveries were 100.5%, 104.1% and 105.2%, respectively, with RSD<4%(n=6). The LOQs (S/N=10) of impurities A, C and D were 31.8, 6.99 and 15.5 ng·mL-1 respectively. The contents of impurities A, C and D in the three samples were all below the limits. CONCLUSION The developed LC-MS method is simple, sensitive, and applicable, which can be used to simultaneously determine impurities A, C and D in caspofungin acetate and can also provide a reference for the detection of other impurities in caspofungin acetate.

OBJECTIVE To analyze caspofungin acetate and the samples under different strong degradation conditions by LC-QTOF-MS, and to study the characteristics in mass spectra of caspofungin and its related impurities(impurities A, B, C, D and E). METHODS Chromatographic separation was accomplished on Waters CORTECS® C18+(4.6 mm×150 mm, 2.7 μm) column using a gradient elution with monile phase of 0.1% formic acid-H2O(A) and 0.1% formic acid-CH3CN(B) at a flow velocity of 0.6 mL·min-1; The analytes was detected in positive ion scan mode by ESI-QTOF-MS. RESULTS In MS1 spectra, except that impurity D mainly showed single-charge quasi-molecular ion, caspofungin and the other four impurities showed muti-charge quasi-molecular ions with high abundance; In MS2 spectra, caspofungin and its impurities that containing ethylenediamine generated fragment ions at m/z 1 033 by losing the ethylenediamine and the groups attached to it; caspofungin and its impurities produced a series of fragment ions mainly through the cleavage of peptide bonds, as well as through the loss of hydroxyl, acyl, or amino groups from amino acid residues; Impurity A and C showed characteristic fragment ions m/z 137.070 8 and m/z 77.071 1 with high abundance, respectively, which could be used to distinguish them from caspofungin and the other impurities. CONCLUSION Caspofungin and its five impurities have distict characteristics in their mass spectra. The research results can provide reference for identifying the structures of unknown impurities that may occur in the production process of caspofungin, so as to quickly discover the potential problems in the production process and reduce the quality risk of the products.