Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Human milk is universally recognized as the optimal and most natural source of nutrition for newborns, offering benefits that extend far beyond basic energy and macronutrient provision. Among its complex constituents, human milk oligosaccharides (HMOs) represent the third most abundant solid component, surpassed only by lactose and lipids. HMOs are distinguished by their exceptionally high structural diversity—over 200 distinct structures have been identified to date. This structural complexity underlies the extensive biological functions HMOs perform within the infant’s body. HMOs play a pivotal role in promoting healthy growth, development, and overall well-being in infants and young children, functioning as indispensable bioactive molecules. Their key physiological activities include: immunomodulation and allergy prevention by promoting immune tolerance and reducing the risk of allergic diseases; potent anti-inflammatory and antioxidant effects that protect vulnerable infant tissues; support for brain development and cognitive enhancement through multiple mechanisms; anti-pathogenic properties, acting as soluble receptor analogs or “decoy” molecules to competitively block viral, bacterial, and other pathogen adhesion, thereby preventing colonization and infection in the gastrointestinal tract; and functioning as blood group substances. At the translational and application level, HMO research is actively driving cross-disciplinary innovation. Building on a deep understanding of their immunological and neurodevelopmental benefits, certain structurally defined HMOs have been successfully incorporated into infant formula. These HMO-supplemented formulas have received regulatory approval and are now commercially available worldwide, providing a nutritional alternative that more closely resembles human milk for infants who are not exclusively breastfed. This represents a significant step toward narrowing the compositional gap between formula and breast milk. Simultaneously, research into the symbiotic relationship between HMOs and the gut microbiota—particularly their role as selective prebiotic substrates promoting the growth of beneficial bacteria—has catalyzed the development of novel functional foods, dietary supplements, and microbiome-targeted therapies. These include advanced synbiotic formulations that combine specific probiotic strains with HMOs to synergistically optimize gut health and function. Furthermore, the intrinsic qualities of HMOs—including their natural origin, safety profile, biocompatibility, and proven antioxidant properties—have attracted growing interest in the emerging field of high-performance cosmetics. They are increasingly being explored as innovative functional ingredients in skincare products aimed at reducing oxidative stress and supporting skin health. This review aims to systematically synthesize recent advancements in HMO research, offering a comprehensive analysis centered on their complex composition and structural diversity; the molecular and cellular mechanisms underlying their diverse biological functions; their translational potential across sectors such as nutrition, medicine, and consumer care (including cosmetics); and the major challenges that persist in the field. It critically examines both foundational discoveries and recent breakthroughs. By integrating these interconnected themes, the review provides a holistic and up-to-date perspective on the scientific landscape of HMOs, highlighting their essential role in early-life nutrition and their expanding relevance across health and wellness applications. It also outlines promising directions for future research, with the goal of advancing evidence-based innovation in infant health and beyond.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

This study was aimed at providing basic data for the control and prevention of Yersinia enterocolitica(Ye)infections.Ye isolates from stool samples collected from patients with diarrhea in a Beijing district between January 2019 and June 2024 were studied.Basic patient information and stool samples were collected,and quantitative polymerase chain reaction(qPCR)was applied to enriched cultures.Further analyses included virulence gene detection,whole-genome sequencing,and drug resistance detection.The detection rate of Ye was 0.76%(11/1 439),according to culture methods,thus yielding 12 Ye strains from distinct patients:11 isolated during the study period and 1 from 2017.The 12 Ye positive patients were 6-41 years of age,and their clinical presentations predominantly featured watery stools(66.67%,8/12)and loose stools(33.33%,4/12).The frequencies of nausea,vomiting,and fever were 41.67%(5/12),41.67%(5/12),and 8.33%(1/12),respectively.The drug resistance rates of Ye to TET,AMP,and NAL were 50.00%(6/12),33.33%(4/12),and 25.00%(3/12),respectively.One Ye strain exhibited multidrug resistance to ETP,MEM,TET,CIP,NAL,and AMP.According to qPCR detection of five common virulence genes,two Ye strains were identified as ystA+/ystB-type(ystA+/ystB-/ail+/yadA+/virF+),whereas ten strains were identified as ystA-/ystB+type(ystA-/ystB+/ail-/yadA-/virF-).VFDB database analysis based on genome sequences indicated that 12 Ye strains carried an average of 11 key virulence genes associated with adhesion,invasion,protease activity,and flagellar movement,and predicted 106 virulence genes and 12 virulence gene profiles.Only the two ystA+/ystB-Ye strains contained elements related to the TTSS and ABC transporter function.Detection of ystA-/ystB+Ye in stool isolation and culture of diarrhea cases might potentially have been missed in some cases,thus highlighting the importance of fluorescence PCR screening of fecal growth solutions to enhance isolation efficiency.Moreover,our findings revealed the genetic diversity of Ye isolated from diarrhea cases,thereby indicating the presence of multiple types of virulence genes within this pathogen.

Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.

Objective:To assess the presence of chemotherapy-induced abnormal myocardial perfusion using SPECT myocardial perfusion imaging (MPI) in patients with malignant hematologic diseases before hematopoietic stem cell transplantation (HSCT), and to explore its predictive value for mid-to-long-term mortality risk after transplantation.Methods:From March 2016 to August 2022, 139 patients with malignant hematologic diseases (80 males, 59 females; age (45.7±13.0) years) who underwent resting MPI to assess the presence of chemotherapy-induced abnormal myocardial perfusion before HSCT at the First People′s Hospital of Changzhou were prospectively included. Baseline-data were collected and patients were followed up for mid-to-long-term (≥100d) adverse outcomes after transplantation. Overall survival (OS) of each patient was recorded. The χ2 test and independent-sample t test were used for data analysis. Cox regression analysis was utilized to identify independent risk factors affecting OS. Kaplan-Meier method and log-rank test were used for survival analysis. Results:The median follow-up time of 139 patients was 41.6(19.5, 65.6) months, with all-cause mortality of 28.8%(40/139), and the cardiovascular mortality was 42.5%(17/40). The prior cardiotoxic therapies rate (anthracycline dose ≥250mg/m 2) was higher in the death group compared to that in the survival group (15.0% (6/40) vs 5.1% (5/99); χ2=3.87, P=0.049). Pre-transplant abnormal myocardial perfusion rate was also higher in the death group compared to that in the survival group (55.0%(22/40) vs 22.2%(22/99); χ2=15.19, P<0.001). But pre-transplant left ventricular ejection fraction (LVEF) was lower in the death group compared to that in the survival group ((60.4±5.2)% vs (62.9±3.9)%; t=-3.07, P=0.003). Cox multivariate regression analysis showed that the abnormal myocardial perfusion indicated by MPI before transplantation was an independent risk factor affecting OS after HSCT in patients with malignant hematologic diseases (hazard rate ( HR)=2.70, 95% CI: 1.33-5.46, P=0.006). Kaplan-Meier analysis showed the 1-, 2-, 5-year OS rates of patients with the abnormal myocardial perfusion and the normal myocardial perfusion were 73.5%, 69.1%, 49.2% and 94.6%, 89.9%, 81.6%, respectively, with significant difference ( χ2=17.01, P<0.001). Conclusions:Patients with abnormal myocardial perfusion detected by MPI before HSCT for malignant hematologic diseases have a poorer prognosis, characterized by lower post-transplantation OS rates. The utilization of MPI for assessing abnormal myocardial perfusion before transplantation in patients with malignant hematologic diseases can aid in predicting the mid-to-long-term mortality risk after transplantation.