ObjectiveTo evaluate a third-generation applicator template for intracavitary combined with interstitial brachytherapy （IC-ISBT） suitable for locally advanced cervical cancer， aiming to improve therapeutic outcomes. MethodsA retrospective study was conducted on patients with stage IB3-ⅣB cervical cancer treated at Sun Yat-sen University Cancer Center from January 2023 to October 2023. Magnetic resonance imaging data before and after external beam radiation therapy were collected and analyzed. According to the residual tumor after external beam radiation， high-risk clinical target volumes （HR-CTV） were delineated， based on which a third-generation IC-ISBT applicator template was designed. The dosimetric and therapeutic differences between using this applicator template （template implantation group） and traditional freehand interstitial implantation （freehand implantation group） were further compared. Statistical methods were used to analyze the data from both groups to test the efficacy and safety of the two approaches. ResultsThe third-generation applicator template could accommodate different cervical structures and optimize needle path layout. The tumor volume in the template implantation group was significantly larger than in the freehand implantation group， showing statistical differences. In terms of dosimetric coverage （V_100%）， the template implantation group exhibited significant statistical differences compared with the freehand implantation group， demonstrating superior dose coverage. Additionally， the third-generation template showed advantages in protecting the rectum and sigmoid colon by potentially reducing high-dose points， while there were no significant differences in bladder dosimetry between the two methods. The primary cervical lesion remission rates were similar between the two groups. ConclusionThe third-generation IC-ISBT applicator template is scientifically and rationally designed， especially for patients with larger tumor volumes and later stages. It is easy to operate， highly reproducible， and shows significant advantages in dose distribution and protection of surrounding critical organs. The template has the potential to be widely applied as a routine treatment option.

As a novel long-acting glucagon-like peptide-1 （GLP-1） receptor agonist， semaglutide plays a pivotal role in the treatment of obesity and related metabolic diseases. This article systematically reviews the research progress of semaglutide in the treatment of obesity and related metabolic diseases from three aspects： mechanism of action， clinical applications， and existing challenges. It is found that its mechanism of action involves multi-organ synergistic regulation and metabolic intervention. Its clinical applications encompass the treatment of obesity， diabetes， polycystic ovary syndrome， and liver-related metabolic syndromes， and it demonstrates groundbreaking value in cardiovascular and renal protection. However， it still faces multiple challenges in terms of adverse reactions， individualized treatment， economic accessibility， ethical controversies， and risks. In the future， it is essential to further accumulate long-term safety data on semaglutide， optimize combination treatment regimens， and address key issues such as individualized medication for special populations， in order to fully realize its clinical application value.

With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.

Objective:To analyze the safety and efficacy of PD-1 inhibitors versus chemotherapy or ipilimumab in advanced melanoma.Methods:PubMed,CNKI,VIP and Wanfang databases were searched to collect randomised controlled trials of PD-1 inhibi-tors in treatment of advanced melanoma.The search time was from the establishment of the database to May 1,2022.Two reviewers independently screened the literature,extracted data,and assessed risk of bias of included studies.Meta-analysis was performed using RevMan5.4 and STATA16 software.Results:A total of 7 studies were included.Meta-analysis results show that:①Safety:Compared with chemotherapy,PD-1 inhibitor treatment had fewer adverse events,especially in the blood system;compared with ipilimumab alone,PD-1 inhibitor combined with ipilimumab had more adverse events,especially liver function indicators;there was no signifi-cant difference in the incidence of total adverse events between PD-1 inhibitor monotherapy and ipilimumab monotherapy.②Efficacy:The PFS,OS and ORR of PD-1 inhibitor versus chemotherapy or ipilimumab were HR=0.54,95%CI(0.45,0.62),P<0.05,HR= 0.69,95%CI(0.58,0.80),P=0.03 and OR=3.16,95%CI(2.59,3.86),P<0.05,respectively.Conclusion:PD-1 inhibitors have good efficacy in treatment of advanced melanoma,while different combination methods and different control treatments may have different efficacy.Limited by the quantity and quality of included studies,more research evidence is needed to support this.

Objective　To explore the clinical characteristics and drug resistance of Elizabethkingia meningoseptica (EM) nosocomial infection, so as to provide evidence for prevention of EM nosocomial infection and guiding the rational use of antibiotics. Methods　A retrospective study was conducted of 67 patients with EM infection in a tertiary hospital from January 2021 to December 2022. The infective characteristics and drug resistance were analyzed. Results　The cohort of 67 EM-infected patients was predominantly males aged ≥60 years, with the most frequent source being the first district of the intensive care unit (ICU), followed by the respiratory medicine and emergency department (19.40%, 13/67). The specimens were mainly isolated from respiratory tract (86.57%, 58/67), of which sputum accounted for 49.25% (33/67), and alveolar lavage fluid accounted for 37.31% (25/67). The majority of EM infections occurred in patients with pre-existing respiratory conditions (49.25%, 33/67), who generally experienced prolonged hospital stays and underwent invasive procedures, such as mechanical ventilation 94.03% (63/67), urinary catheterization (95.52%, 64/67), and central venous catheterization (97.01%, 65/67). Post-treatment, the improved rate of the 67 patients was 40.30% (27/67). Susceptibility testing demonstrated a high resistance rate of EM to cefoperazone-sulbactam, 98.39% (61/62), contrasted by significant susceptibility to compound trimethoprim-sulfamethoxazole (TMP-SMX)/cotrimoxazole, doxycycline, minocycline, and piperacillin-tazobactam, with susceptibility rates exceeding 90%. Conclusions　The patients infected with EM were almost elderly men with certain underlying diseases, experienced prolonged hospital stays, and had a history of invasive operations. The specimens of EM were mainly from Intensive Care Unit and isolated from respiratory tract. The strain showed high resistance to cefoperazone-sulbactam, whereas it remained highly susceptible to cotrimoxazole, doxycycline, minocycline and piperacillin-tazobactam, which may be considered as first-line treatment options.

Objective To invesigate the feasibility of low radiation dose and low contrast dosage in triple-rule-out computed tomo-graphy angiography(TRO-CTA)on the 320-row detector CT.Methods A total of 120 patients who underwent CTA were prospec-tively selected.All patients were divided into control group(n=90)and experimental group(n=30).The control group employed standard-doses protocol of pulmonary CTA(120 kV tube voltage,45 mL contrast dosage),coronary CTA(120 kV,50-60 mL),and aortic CTA(120 kV,75 mL),while the experimental group received TRO-CTA with 100 kV and 70-80 mL.The peak time of contrast dosage at the pulmonary artery and aorta was measured by low-dose detection method in the experimental group,and the contrast examination was performed sequentially in the control group.Subjective scores and objective image quality of the pulmonary artery,coronary artery,and aorta in the experimental group and the control group were measured and compared,respectively.The effective dose(ED)between the two groups were recorded and compared.Independent samples t-test and Fisher exact probability were used to analyze the statistical differences between the above measures.Results There were no significant differences in CT values,con-trast-to-noise ratio(CNR),signal-to-noise ratio(SNR)of pulmonary artery,coronary artery and aorta between the two groups(P＞0.05).The mean subjective scores of pulmonary artery,coronary artery and aorta segments in the two groups were not less than 3 points,meeting the requirement of clinical diagnosis.There was no statistical difference in subjective scores between the two groups(P＞0.05).There was statistically significant difference in ED between the two groups(P＜0.05).The ED of pulmonary artery,coronary artery,and aorta in the experimental group were 11.49％,13.33％,and 11.46％significantly lower than those in the control group,respec-tively.Conclusion It is feasible to obtain TRO-CTA images used by the low radiation dose and low contrast dosage on the 320-row detector CT,and radiation dose and contrast dosage can be reduced reasonably without alterations of TRO-CTA images quality in clinical practice.

Objective:To compare with video-fluoroscopic swallowing function test(VFSS),so as to evaluate the application value of ultrasonography in the test of dysphagia after stroke.Methods:A total of seventy-two patients with dysphagia after stroke who admitted to The Second Affiliated Hospital of Hainan Medical University from January 2022 to July 2023 were selected as cases group,and a total of 45 healthy aged with normal swallowing function were selected as healthy control group at the same time.All of them underwent video X-ray fluoroscopic examination of swallowing function and quantitative assessment of ultrasound.Quantitative assessment of ultrasound was performed by twice to compare the internal consistency of ultrasound test.Meanwhile,the correlation between ultrasound and VFSS results was tested to verify the validity of ultrasound quantitative assessment.The VFSS was used as gold standard to analyze the sensitivity and specificity of ultrasound assessment.The differences of abnormal grade of Geniohyoid muscle;movement time,movement distance and the change of tongue muscle thickness of semi quantitative description of ultrasound between two groups were compared.Results:The intra group correlation coefficient(ICC),movement time,movement distance and movement speed of grade description of muscle abnormalities of cases group were respectively 0.90,(1.743±0.235)s,(6.323±0.823)mm and(3.826±0.778)mm/s,which intra reliabilities were high correlation(ICC=0.90,0.82,0.87,0.85,P＜0.01),which inter reliabilities of these indicators were high correlation(ICC=0.86,0.85,0.88,0.87,P＜0.01),respectively.The positive results of ultrasound test highly correlated with the results of VFSS examination(r=0.91,P＜0.01).The movement distance,the average movement speed and the changes of the thickness of tongue muscle in patients of cases group were significantly smaller than those of healthy control group,but the movement time was larger than that of healthy control group(t=9.03,30.49,-7.02,22.69,P＜0.05),respectively.The results of the ultrasound on the muscles of all patients in cases group existed abnormality.Conclusion:Ultrasound technique can quantitatively assess dysphagia after stroke.Compared with VFSS technique,ultrasonography can measure and determine the related data of the movement of swallowing muscle,and dynamically record movement parameters of geniohyoid muscle and the changes of the thickness of tongue muscle.At the same time,it can detect the grade of muscle abnormalities of patients with dysphagia,which will contribute to further explore the potential pathological mechanism about muscle,and promote the healthy management for patients with dysphagia.

Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca²⁺ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.
Mice ; Animals ; Reproducibility of Results ; Neurons ; Sensation ; Perception

BackgroundThe treatment of patients with depressive disorders is short of targeted outcome assessment. As a secondary outcome that is guided by patient values， quality of life is thus of relatively high evaluative value. In China， there exists a lack of large sample prospective cohort studies evaluating the effect of different treatment protocols on quality of life in patients with acute depressive disorder. ObjectiveTo explore the effects of monotherapy and combination therapy on the quality of life of patients with depressive disorder in acute phase， so as to provide references for optimizing the outcome of treatment for such patients. MethodsA prospective follow-up cohort study from August 24， 2020 to November 29， 2021 was conducted， including 1 330 patients from 22 hospitals across 18 cities in China. All these patients met the diagnostic criteria for depressive episodes， recurrent depressive disorder from the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Patients were divided into monotherapy group （n=969） and combination therapy group （n=361） according to the acute phase treatment protocol. At baseline， the end of the first half month as well as the 1^st， 2^nd， 3^rd， 6^th， 9^th and 12^th months of treatment， patients were assessed with Inventory of Depressive Symptomatology Self-report （IDS-SR30）， Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form （Q-LES-Q-SF）， Concise Health Risk Tracking Scale （CHRT） and Siehan Disability Scale （SDS）. Frequency， Intensity， and Burden of Side Effects Rating （FIBSER） was adopted for assessment at each visit time point of treatment. Spearman correlation analysis was adopted to examine the correlation of quality of life with suicide risk， adverse reactions and impaired social functioning among patients. ResultsAt the end of three months of treatment， the Q-LES-Q-SF score of monotherapy group was higher than that of combination therapy group， and the difference was statistically significant （Z=2.008， P<0.05）. The time effects of both treatment protocols possessed statistical significance （F=111.393， P<0.01）. At the end of three months of treatment， the Q-LES-Q-SF score was negatively correlated with CHRT and SDS scores， respectively， in both monotherapy group and combination treatment group （r=-0.660， -0.712， -0.634， -0.718， P<0.01）. ConclusionBoth monotherapy and combination therapy can facilitate the improvement of the life quality of patients with acute depressive disorder， but monotherapy may achieve better than the combination therapy in this aspect. ［Funded by The National Key Research and Development Program of China "Research on the Prevention and Control of Major Chronic Non-communicable Diseases" （number， 2017YFC1311101）］

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*