Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the tumors.Therefore,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned.As carbonic anhydrase Ⅸ(CA Ⅸ)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfo-namide(ABS)as a CA Ⅸ inhibitor has inherent inhibitory activity and good targeting effect.In this study,Ag2S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bio-probe(Ag2S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation reaction.Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor im-aging by the near infrared-Ⅱ(NIR-Ⅱ)fluorescence characteristics of Ag2S QDs.PEG modification of Ag2S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal sta-bility and high photothermal conversion efficiency(PCE)of 45.17％.Under laser irradiation,Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in vitro.It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility.Therefore,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*

Objective:To analyze the efficacy of the new forest parenting programme (NFPP) for children and families with attention deficit hyperactivity disorder (ADHD) in China, and to explore the feasibility and effectiveness of the programme in China.Methods:Twenty-two children with ADHD diagnosed at the Child Psychology Development and Behavior Outpatient Clinic of the First Affiliated Hospital of Jinan University and their primary caregivers were included in the study from January 2022 to May 2023. The children with ADHD were divided into an experimental group ( n=11) and a control group ( n=11) according to the personal preference of the primary caregivers. The experimental group was provided with the NFPP intervention once a week for a period of 8 weeks. The Chinese version of Swanson Nolan and Pelham, version Ⅳ scale-parent form(SNAP-Ⅳ)and Weiss functional impairment rating scales-parent report(WFIRS-P))were used to assess the improvement of core symptoms and social function impairment in the two groups before and after the intervention. In the experimental group, the Chinese parenting sense of competence scale (C-PSOC) and the parenting styles and dimensions questionnaire (PSDQ) were used to evaluate the parenting efficiency and improvement of parenting styles of primary caregivers in ADHD families before and after NFPP intervention. A Semi-open interview was conducted with 11 primary caregivers of ADHD children in the experimental group at the end of the intervention regarding knowledge of ADHD disease diagnosis and treatment, parenting attitudes, and parenting behaviors. The data was statistically analyzed by SPSS 26.0 software.Statistical analysis of data was used by independent sample t-test, paired sample t-test, Mann Whitney U-test, and rank sum test. Results:(1) Compared with the post-intervention control group, the total score((4.01±1.05), (2.79±0.94), t=2.875, P<0.05) in the SNAP-Ⅳ, the scores of the oppositional defiance dimension((1.27±0.34), (0.70±0.33), t=4.043, P<0.05) in the SNAP-Ⅳ, the scores of the family in WFIRS-P ((0.92±0.47), (0.56±0.26), t=2.246, P<0.05), and the scores of life skills in WFIRS-P (1.1(0.9, 1.3), (0.6(0.5, 0.8), Z=-2.013, P<0.05)were significantly lower in the post-intervention experimental group ( P<0.05). After intervention, the scores of the 3 dimensions of attention deficit, impulsivity/hyperactivity, and oppositional defiance and the total score of the SNAP-Ⅳ in the experimental group were significantly lower than those before intervention (all P<0.05). (2) After intervention, the score of the parenting efficacy dimension in the C-PSOC in experimental group was significantly higher than pre-intervention ( P<0.05). After intervention, the scores of the PSDQ for authoritative parenting style in the self-assessment and other-assessment in the experimental group were significantly higher than pre-intervention (all P<0.05), and the scores of the authoritarian parenting style and the permissive parenting style were significantly lower than pre-intervention (all P<0.05). (3) The results of the semi-open interview suggested that, the primary caregivers of children with ADHD in the experimental group had a positive attitude toward the NFPP intervention and were able to participate in the entire 8-week intervention, and apply the learned parenting skills to daily life to continuously improve parenting efficiency. After the NFPP intervention, the primary caregivers of children with ADHD had a deeper understanding of the knowledge of ADHD diseases, behavioral characteristics of children with ADHD, and so on. In the intervention content, the modules such as time management, communication skills and behavioral prediction were easy to grasp and effective. Conclusion:The NFPP can significantly improve the core symptoms of Chinese children with ADHD, increase the parenting efficacy of their primary caregivers, and improve their parenting styles.

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor

Objective:To analyze the clinical characteristics and short-term prognosis of patients with acute asthmatic attack and comorbid bronchiectasis.Methods:The data of patients hospitalized for acute asthmatic attack in the Department of Respiratory and Critical Care Medicine of Peking University Third Hospital from January 1, 2012 to December 31, 2021 were retrospectively collected and analyzed. According to whether or not co-existing with bronchiectasis, all the patients were divided into asthmatic with bronchiectasis group and asthmatic without bronchiectasis group. Then the general conditions, comorbidities, pulmonary function test, grades of asthma severity, laboratory examination and in-hospital short-term prognosis of two groups were analyzed.Results:A total of 580 hospitalized patients with acute asthma attack were included, of which 132 cases (22.76%) were classified into asthmatic with bronchiectasis group and 448 cases (77.24%) were classified into asthmatic without bronchiectasis group. Co-existing with obsolete pulmonary tuberculosis and anxiety/depression in asthmatic with bronchiectasis group were more common than that in asthmatic without bronchiectasis group (13.64% vs 5.36%; 7.58% vs 2.68%) (both P<0.05). The pre-bronchodilator forced vital capacity (FVC) and its percentage to the predicted value (FVC%pred), forced expiratory volume in 1 second (FEV 1) and its percentage to the predicted value (FEV 1%pred), FEV 1/FVC and post-bronchodilator FEV 1 in asthmatic with bronchiectasis group were lower than those in the asthmatic without bronchiectasis group [2.44 (1.90, 3.01) vs 2.69 (2.10, 3.68) L, 1.55 (1.13, 2.00) vs 1.78 (1.25, 2.52) L, 70.14% (67.39%, 85.92%) vs 79.63% (70.00%, 89.52%), 70.00% (54.38%, 78.11%) vs 70.00% (61.47%, 85.00%), 61.57% (56.29%, 73.03%) vs 66.67% (60.00%, 75.00%), 1.72 (1.21, 2.18) vs 1.89 (1.37, 2.55) L] (all P<0.05). In previous year, the proportion of patients receiving hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group was higher than that in asthmatic without bronchiectasis group (15.15% vs 8.93%) ( P<0.05). The peak months of hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group were April, July and October, and the peak months in asthmatic without bronchiectasis group were April and September. The length of hospital stay was longer and the proportion of patients receiving invasive ventilation was higher in asthmatic with bronchiectasis group than those in asthmatic without bronchiectasis group [10.06 (7.62, 13.94) vs 9.95 (7.15, 13.76) d; 5.30% vs 2.01%] (both P<0.05). The risk factors for invasive mechanical ventilation in asthmatic patients with acute attack during hospitalization were co-existing with bronchiectasis, smoking, high level of partial pressure of carbon dioxide in arterial blood, serum creatinine and creatine kinase. Conclusion:Asthma patients with comorbid bronchiectasis have more frequent acute attack, a longer hospitalization due to acute asthmatic attack and a higher probability of invasive ventilation during hospitalization.

Micheliolide is a kind of guaiacane sesquiterpene lactone from natural plants. It distributs in the root bark of Cephalantheropsis gracilis and Michelia compressa . Modern pharmacological studies show that ，micheliolide can play an anti-tumor role by inhibiting the proliferation of tumor cells ，regulating the apoptosis of tumor cells ，inducing autophagy of tumor cells ，and inhibiting invasion and metastasis of tumor cells. It can reduce the expression of inflammatory cytokines by regulating several related signaling pathways ，such as nuclear factor κB and phosphatidylinositol-3-hydroxykinase/protein kinase B ；it can play an immunomodulatory role by restoring the expression of immune-related factors in the body ；it can play a neuroprotective effect by reducing the accumulation of amyloid β-protein and inhibiting microglial activation ；it can play a liver protective role by reducing the inflammatory response and steatosis of hepatocytes ；its nephroprotective mechanism is related to the relief of the inflammatory response by regulating multiple pathways ；the mechanisms of its cardioprotective action include alleviating the inflammatory response and reducing the level of oxidative stress ，etc. In conclusion ，micheliolide is a compound of great development value.

It is clear that organoids are useful for studying the structure as well as the functions of organs and tissues; they are able to simulate cell-to-cell interactions, symmetrical and asymmetric division, proliferation, and migration of different cell groups. Some progress has been made using brain organoids to elucidate the genetic basis of certain neurodevelopmental disorders. Such as Parkinson's disease and Alzheimer's disease. However, research on organoids in early neural development has received insufficient attention, especially that focusing on neural tube precursors. In this review, we focus on the recent research progress on neural tube organoids and discuss both their challenges and potential solutions.
Humans ; Organoids ; Neural Tube ; Neurodevelopmental Disorders/genetics* ; Brain ; Alzheimer Disease

Objective:To explore the independent risk factors that predict 10-year mortality in patients with stable chronic obstructive pulmonary disease(COPD).Methods:The baseline data from a prospective cohort study were analyzed and long-term follow-up were performed. Patients with confirmed diagnosis of stable COPD were consecutively enrolled in the outpatient clinic from January 2010 to December 2010, and were followed up until December 31, 2020. Cox regression analysis was used to determine the independent risk factors for all-cause mortality and mortality from respiratory causes in stable COPD patients.Results:A total of 182 stable COPD patients were enrolled and followed up for a median of 89 months. The 10-year mortality was 51.1%(93/182), and 9 patients died within one year. The leading cause of death was respiratory disorder, followed by cardiovascular and cerebrovascular diseases. The risk factors independently associated with all-cause mortality included old age( HR=1.936,95% CI: 1.610~2.328, P<0.01), increased baseline COPD Assessment Test(CAT)( HR=1.331,95% CI: 1.049-1.689, P=0.02) and the increased CAT in one year( HR=1.314,95% CI: 1.197-1.420, P<0.01). The risk factors independently associated with respiratory cause mortality included increased baseline CAT( HR=1.719,95% CI: 1.026-2.880, P=0.04), emphysema index(LAA%)( HR=1.062,95% CI: 1.007-1.120, P=0.03), and one year inecreased CAT( HR=1.342,95% CI: 1.198-1.505, P<0.01)was a protective factor. Conclusions:Old age, baseline CAT, one year increased in CAT and LAA% were independent influencing factors for 10-year mortality of stable COPD patients.

Objective:To preliminarily observe the clinical efficacy of microwave hyperthermia combined with intensity-modulated radiotherapy (IMRT) and chemotherapy for patients with locally advanced gastric cancer.Methods:Forty patients who could not been operated or refused operation were enrolled in this clinical trial, who were confirmed as locally advanced proximal or distal gastric cancer by gastroscopy pathology and imaging. Radiotherapy was delivered by IMRT technology for 5 times per week with a total dose of 46 to 56 Gy (median dose of 50 Gy) in 25 to 28 fractions. Synchronous hyperthermia was given at 42 to 44℃ twice a week, 45 min/time. S-1 or capecitabine-based synchronous chemotherapy was performed, d1-14/3 weeks. The symptom remission rate, adverse reactions, objective remission rate (complete and partial remission) and survival were observed.Results:A total of 40 patients, aged between 56 and 83 years (median age of 71 years), were enrolled in this study. The male-to-female ratio was 7: 1. Among them, 38 cases (95%) showed symptom remission. The most common adverse reactions were grade 1-2 gastrointestinal reactions and leukopenia. The objective remission rate was 87.5%, the 2-year progression-free survival and overall survival rates were 68.6% and 70.5%, respectively.Conclusion:Preliminary findings demonstrate that microwave hyperthermia combined with chemoradiotherapy achieve satisfactory outcomes and yield tolerable toxicity in patients with locally advanced gastric cancer.