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.

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.
Humans ; Lysosomes/physiology* ; Autophagy/physiology* ; Nanomedicine/methods* ; Neurodegenerative Diseases/therapy* ; Animals ; Nanostructures ; Lysosomal Storage Diseases/therapy*

BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective　To investigate the contamination status of Bacillus cereus in food, the profile of virulence factors carried, and drug sensitivity characteristics in Liaoning Province. Methods　A total of 620 samples were isolated from 15 monitoring sites, covering four major sample types of food products in Liaoning Province between 2021 and 2022. Bacillus cereus was isolated and identified by GB4789.14—2014, and its virulence was assessed using PCR detection of the groEL and gyrB genes specific to the bacterial group, as well as 11 other virulence genes. Broth microdilution method was used to detect the antibiotic sensitivity of the strain. Results　All 79 Bacillus cereus strains were found to carry virulence genes. The detection rates of non-hemolytic enterotoxin genes nheC, nheA, and nheB were 100% (79/79), 93.3% (74/79), and 83.5% (66/79), respectively. The detection rate of enterotoxin entFM gene was 98.7% (78/79). The 79 strains of Bacillus cereus carried 19 types of virulence gene patterns, with IX and XVII gene patterns being the most prevalent, each accounted for 16.5% (13/79). The resistance rates of 79 strains of Bacillus cereus to 10 antibacterial drugs were 100% for both ampicillin and penicillin. The resistance rates to cotrimoxazole, imipenem, erythromycin, clindamycin, ciprofloxacin, and tetracycline 65.8% (52/79), 10.1% (8/79), 73.4% (58/79), 60.8% (48/79), 75.9% (60/79), and 70.9% (56/79) respectively. The resistance rates to chloramphenicol and gentamicin were both 0%. Conclusion　Food from catering services in Liaoning Province shows contamination by Bacillus cereus, with isolated strains carrying at least four kinds of virulence genes. About 100% of the isolates were resistant to ampicillin and penicillin, whereas high sensitivity was observed to chloramphenicol and gentamicin. Active monitoring, timely targeted prevention and control interventions should be strengthened to provide a theoretical basis for future traceability studies.

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.

Ophthalmic drug-device combination products are a new method of ophthalmic disease treatment,which is characterized by high bioavailability,strong targeting and good compliance.However,it is difficult for products to be developed and regulated due to the complexity of the human eye structure,drug-device interactions,and other factors.To provide a basis for guaranteeing the safety and efficacy of products development and management,the related regulations,current research,and evaluation of the quality of products are summarized in this paper.

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.

Objective:To investigate the effect of prenatal dexamethasone on short-term outcomes and long-term neurological development in late preterm infants with twin pregnancy.Methods:A total of 315 pregnant women with twin pregnancy and their preterm infants who delivered in Peking University Third Hospital from January 2019 to December 2022 were retrospectively analyzed. The clinical data of pregnant women and preterm infants were collected. They were divided into non-medication group (93 pregnant women and 186 preterm infants), medication after 34 weeks group (123 pregnant women and 246 preterm infants), and medication before 34 weeks group (99 pregnant women and 198 preterm infants). Short-term outcomes of preterm infants were analyzed, including the incidence of neonatal respiratory distress syndrome (NRDS), wet lung, hypoglycemia, neonatal septicemia, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and neonatal necrotizing enterocolitis (NEC). "Ages and Stages Questionnaire-Third Edition (ASQ-3) scale" was used to follow up the late neurological development of preterm infants at the corrected age of 6-54 months, and the level of neurological development was compared.Results:(1) General conditions: the gestational age at delivery in the non-medication group [36.1 weeks (35.6, 36.6 weeks)] was later than that in the medication after 34 weeks group [36.1 weeks (35.2, 36.4 weeks)] and medication before 34 weeks group [35.2 weeks (34.2, 36.2 weeks)] groups, and the differences were statistically significant (all P<0.05). After correcting for gestational age, there was no significant difference in birth weight among the three groups ( H=3.808, P=0.149). There were no significant differences in gender and the proportion of small for gestational age among the three groups (all P>0.05). (2) Short-term outcome: the incidence of wet lung was 7.0% (13/186), 11.0% (27/246) and 16.2% (32/198) in the non-medication group, medication after 34 weeks group and medication before 34 weeks group, respectively, and the difference was statistically significant ( P=0.018). There were no significant differences in the incidence rates of NRDS, hypoglycemia, sepsis, IVH, BPD, and NEC among the three groups (all P>0.05). Logistic regression analysis with gestational age and newborn birth weight as confounding factors showed that early gestational age ( OR=0.884, 95% CI: 0.837-0.933, P<0.001) and increased incidence of selective intrauterine growth restriction type I ( OR=2.967, 95% CI: 1.153-7.639, P=0.024) could both lead to an increased incidence of wet lung. (3) Long-term outcomes: a total of 109 pregnant women completed the follow-up, and 218 preterm infants with a corrected age of 6-54 months at the end of follow-up were enrolled, including 86 cases in the non-medication group, 66 cases in the medication after 34 weeks group, and 66 cases in the medication before 34 weeks group. There were no significant differences in the scores of communication, gross motor, fine motor, problem solving and personal-social among the three groups (all P>0.05). Conclusion:Prenatal administration of a single course of dexamethasone does not affect the neonatal birth weight and short-term outcomes of twin late preterm infants, and has no adverse effect on the neurological development of twin late preterm infants with a corrected age of 6-54 months.

Objective:Analyze the impact of smoking on the mortality and life expectancy of residents in Tianjin in 2019.Methods:Use mortality case-control study method to collect all cause of death cases of residents in Tianjin in 2019 for analysis. After adjusting for the 5-years-old age group, education level, and marital status, the smoking attributed deaths from different diseases of different genders, smoking attributed deaths in different age groups, and their impact on life expectancy were analyzed.Results:The total number of deaths in 2019 was 75 254, with 42 201 males (56.1%). Among male deaths, 3 215 (9.9%) were attributed to smoking, of which 2 157 (50.2%) lung cancer deaths were attributed to smoking; The risk of lung cancer death among smokers was 3.075 times higher than that of non-smokers (95% CI: 2.812-3.364); Among the 33 053 female deaths (43.9%), 1 396 (5.8%) were caused by smoking, with 744 (29.1%) lung cancer deaths attributed to smoking. The age group with the highest number of deaths attributed to smoking for women was the 75-<80 years old age group, followed by the 70-<75 and 80-<85 years old age groups. The age group with the highest proportion of deaths attributed to smoking for men was the 55-<60 years old age group. In addition, smoking accounts for more than 60% of deaths in the 60-<65, 45-<50, 55-<60, and 65-<70 years old age groups. In 2019, the loss of life expectancy attributed to smoking deaths among all residents in Tianjin was 1.13 years, with a loss of 1.15 years for males and 0.57 years for females. The expected life expectancy excluding deaths caused by smoking was 82.92 years, 80.77 years for males and 84.61 years for females. Conclusions:Smoking remains one of the important risk factors for death among residents. Promoting effective measures to reduce smoking rates is an effective way to increase life expectancy.