Objective: To examine the impacts of chemotherapy/radiotherapy, targeted therapy, and combined treatment on the quality of life in patients with intermediate and advanced lung cancer. Methods: The patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy, targeted therapy, and combined treatment for the first time were recruited from a tertiary hospital in Weifang City, Shandong Province, using a quota sampling method in September 2023. Basic information was collected using a general information questionnaire, and the quality of life was assessed using the Chinese version of Functional Assessment of Cancer Therapy-General. The investigation started on the 7th day of treatment, and the follow-ups were conducted at 3 and 6 months. The quality of life in patients with different treatment regimens and at different treatment time were compared using repeated measure analysis of variance. Results: There were 26 chemotherapy/radiotherapy patients, 32 targeted therapy patients, and 95 combination therapy patients. There were no significant differences in age, gender, place of residence, education level, self-rated economic status, medical insurance, pathological type and disease stage among the three treatment regimens (all P>0.05). The repeated measure analysis of variance showed an interaction effect between time and group among patients receiving the three treatment regimens (P<0.05). The quality of life scores of patients receiving combination therapy decreased with extended treatment time (all P<0.05). The quality of life scores of patients receiving targeted therapy at 3 and 6 months were lower than those treated for 7 days (both P<0.05). No significant differences were observed in quality of life scores among chemotherapy/radiotherapy patients with different treatment durations (all P>0.05). At 3 and 6 months, patients receiving combination therapy had lower quality of life scores compared to those receiving chemotherapy/radiotherapy or targeted therapy (all P<0.05). Conclusion The decline in quality of life for patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy and targeted therapy is less than that for patients receiving combined therapy.

[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ²=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.

Chronic heart failure （CHF） is a complex clinical syndrome that the cardiac output is not enough to meet the metabolic needs of the body， or depends on the increase of filling pressure to compensate. Its high morbidity and mortality pose a serious threat to human health， necessitating attention and active intervention. At present， western medicine treatment of CHF is mainly based on diuretics， intravenous vasodilators， intravenous positive inotropic drugs， etc.， which， however， have problems such as long medication cycles， serious side effects， and limited applicable population. Recent studies have shown that traditional Chinese medicine can act in a multi-pathway， multi-component， and multi-target manner， showing unique advantages in the prevention and treatment of CHF. Buyang Huanwutang has the effects of tonifying Qi， activating blood， and dredging collaterals. Clinical and mechanism studies have confirmed that this prescription is effective in treating CHF and its syndromes. The clinical studies can be classified into two categories. Studies of the first category use simple modern medical diagnostic criteria as the inclusion criteria for CHF patients， which can improve the scientificity and objectivity. Studies of the second category uses modern medicine combined with traditional Chinese medicine disease diagnostic criteria for the screening of CHF patients， which helps to improve the accuracy of efficacy evaluation. However， there are problems such as the lack of unified research standards and the insufficiency of mechanism research. In addition， the available studies remain to be classified or summarized. This study systematically sorted out the clinical and mechanism studies of Buyang Huanwutang in the treatment of CHF in recent years to review the research status. In clinical treatment， Buyang Huanwutang can be used alone， or modified， or combined with other prescriptions or Western medicine. The mechanism studies predict that Buyang Huanwutang can ameliorate CHF by regulating the calcium balance， protecting the mitochondrial structure and function， and regulating intestinal flora. This review aims to provide a theoretical basis and practical guidance for the clinical application and optimization and subsequent in-depth study of Buyang Huanwutang in the treatment of CHF.

Objective To explore the mediating effect of sleep quality between somatic symptoms and severity of depression in patients with depression. Methods A total of 384 drug-naive patients diagnosed with depression were recruited from the Department of Psychological Medicine of Zhongshan Hospital, Fudan University, during the period from February to August 2024. The severity of depression, somatic symptoms, and sleep quality were assessed using Patient Health Qusetionaire (PHQ)-9, PHQ-15, and Pittsburgh sleep quality index (PSQI), respectively. Based on the PHQ-15 scores, all participants were stratified into two groups: a mild somatic symptoms group（＜10 points, n＝136）and a moderate-to-severe somatic symptoms group（≥10 points, n＝248）. Comparisons of sleep quality between the two groups were conducted, and partial correlation analysis was performed to examine the correlation between sleep quality and somatic symptoms. Additionally, linear regression and mediation analyses were conducted to investigate the mediating effect of sleep quality between somatic symptoms and severity of depression. Results The PSQI scores in moderate-to-severe somatic symptoms group were significantly higher than those in mild somatic symptoms group (P＜0.001). Partial correlation analysis indicated that, after controlling for depression severity, the positive correlation between PSQI and PHQ-15 scores remained significant in both groups (P＜0.01). Regression analysis identified both sleep quality and somatic symptoms as predictors of severity of depression (P＜0.001). Additionally, mediation analysis demonstrated that sleep quality partially mediated the relationship between somatic symptoms and severity of depression, accounting for 26.63% (0.090/0.338) of the total effect. Conclusions In patients with depression, sleep quality is associated with somatic symptoms, and both contribute to an increased risk of the severity of depression. Moreover, sleep quality plays a partial mediating effect between somatic symptoms and severity of depression, highlighting the importance of addressing sleep-related issues in the management of depression.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Objective:To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).Methods:Clinical data of three children diagnosed with late-onset MADD at the Children′s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.Results:The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c. 1211T>C (p.M404T) and a maternal c. 488-22T>G variant in child 1, a paternal c. 1717C>T (p.Q573X) and a maternal c. 250G>A (p.A84T) variant in child 2, and a paternal c. 1285+ 1G>A and maternal c. 629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q 10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. Conclusion:The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

Objective To identify epidemiological characteristics and pathogen distribution of hand,foot,and mouth disease(HFMD)in Hebei Children's Hospital in order to support prevention and treatment of HFMD.Methods A total of 1 698 cases throat swab samples from children diagnosed as HFMD from 2016 to 2023 were collected.Real-time PCR was used to detect the specific classification of HFMD.Statistical analysis was performed according to the year,season,age,and sex and enterovirus type of HFMD in the children.Results From 2016 to 2023,the ratio of male to female patients among the 1 698 children admitted to Hebei Children's Hospital was 1.72∶1.Among them,the highest incidence rate in summer was 778 cases,accounting for 45.8%of all cases,followed by autumn,with a total of 614 cases,accounting for 36.2%of cases.The highest incidence was recorded in age group of 1-3 years,with a total of 1 032 cases(60.8%).The lowest incidence was 38 cases in age group＞6 years old(2.2%);There were 988 cases of HFM(58.2%)caused by different strains of enterovirus undefined(EVU)except enterovirus 71(EV71)and coxsackievirus A16(CA16).Conclusions HFMD found in Hebei Children's Hospital from 2016 to 2023 are mainly caused by enteroviruses except EV 71 and coxsackievirus A16.High morbid-ity is found in children aged 1-3 years,and summer and autumn are the main epidemic seasons.This result may facilitate and support decision making and strategy development in disease prevention and control as well as to strengthen public health resources.

Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.