This paper systematically elaborates on the key points of diagnosis and differential diagnosis of salivary gland tumors characterized by a substantial amount of extracellular mucus as a main or prominent feature, and clarifies the core differential features. The term "mucus-rich" specifically denotes that mucus is a major component of the tumor, rather than a focal or minor one. This phenomenon is associated with distinct histogenetic mechanisms: it may result from specific genetic mutations (e.g., AKT1 E17K in mucinous adenocarcinoma) that drive ductal epithelial differentiation into mucus-secreting cells, or from myoepithelial cells secreting glycosaminoglycans that form a myxoid stroma. Salivary gland tumors with abundant extracellular mucus include mucinous cystadenoma, sialadenoma papilliferum-like intraductal papillary tumors, mucinous myoepithelioma, pleomorphic adenoma with mucin-rich stroma, mucinous adenocarcinoma, low-grade mucoepidermoid carcinoma, mucin-rich salivary duct carcinoma and intestinal-type adenocarcinoma. The diagnosis of these tumors is complicated by the dual nature of extracellular mucus: while it is a defining feature of some entities, it can also obscure key diagnostic architectural features in others, leading to histological overlap and inconspicuous diagnostic areas. Given the frequent histological morphological overlap among these tumors, immunohistochemical findings and molecular characteristics have emerged as crucial differential diagnostic criteria. Core differential diagnostic points include the following: histologically, there must be meticulous identification of typical structures obscured by mucin (such as squamoid cells in mucoepidermoid carcinoma and apocrine features in salivary duct carcinoma); in immunohistochemical staining, CK20 is useful for distinguishing intestinal-type adenocarcinoma (positive) from mucinous adenocarcinoma (negative), while androgen receptor aids in differentiating salivary duct carcinoma (positive) from mucoepidermoid carcinoma (negative); and molecular testing plays a critical role in definitive diagnosis (e.g., the AKT1 E17K mutation for mucinous adenocarcinoma, MAML2 rearrangement for mucoepidermoid carcinoma, and MEF2C::SS18 fusion for microsecretory adenocarcinoma). This paper systematically summarizes the core pathological features and differential diagnostic points of mucin-rich salivary gland tumors, aiming to provide a practical reference for clinical pathological diagnosis.

ObjectiveThis paper aims to investigate the efficacy and related actions of Guizhi Fulingwan in intervening in the mice with colitis-associated colon cancer （CAC） based on the immunosuppressive microenvironment associated with myeloid-derived suppressor cells （MDSCs）. MethodsSixty male C57BL/6 mice were randomly assigned to a blank group， a model group， an aspirin group （0.04 g·kg^-1）， and low-， medium-， and high-dose Guizhi Fulingwan groups （4.87， 9.75， and 19.50 g·kg^-1）， with ten mice per group. The CAC mouse model was established via combined induction of azoxymethane （AOM）/dextran sulphate sodium （DSS）. Drug intervention commenced in week five， with continuous intragastric administration for nine weeks. The food intake， body weight， fecal characteristics， and haematochezia were observed and recorded， and disease activity index （DAI） scores were calculated according to scoring criteria. Hematoxylin and eosin （HE） staining was used to observe the histopathological changes in the colon tissues of the mice. Immunohistochemistry was used to determine proliferating cell nuclear antigen-67 （Ki67） expression in the colon tissues， and enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） in the serum of the mice. Flow cytometry was employed to determine the proportion levels of MDSCs， CD4⁺ T cells， and CD8⁺ T cells in the spleen tissues of the mice. The mRNA expressions of MDSC-associated effector molecules， including arginase 1 （Arg1） and inducible nitric oxide synthase （iNOS）， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. After that， an in vitro co-culture model of MDSCs and CD8⁺ T cells was established， and drug-containing serum of Guizhi Fulingwan was used for intervention. The Flow cytometry was employed to assess the effects of drug-containing serum of Guizhi Fulingwan with different concentrations on the levels of reactive oxygen species （ROS） and iNOS in MDSCs and the proliferation of CD8⁺ T cells. The levels of granzyme B （GZMB） and interferon-γ （IFN-γ） in cell supernatant were detected by ELISA. ResultsCompared with those in the control group， the mice in the model group exhibited significantly reduced body weight， elevated DAI scores， shortened colon length （P<0.01）， increased number of tumors and Ki67 expression （P<0.01）， and significantly elevated contents of IL-6， IL-1β， and TNF-α in the serum （P<0.01）. Significant increases in the number of MDSCs were observed in mouse spleens， alongside marked reductions in the levels of CD4⁺ T and CD8⁺ T cells （P<0.01）. Furthermore， the mRNA expressions of MDSC function-associated effector molecules Arg1 and iNOS were significantly upregulated （P<0.01）. Compared with those in the model group， the mice in the middle-dose Guizhi Fulingwan group exhibited increased body weight and significantly decreased DAI scores （P<0.05， P<0.01）. The mice in the middle- and high-dose Guizhi Fulingwan groups exhibited significantly improved colon shortening， significantly decreased number of tumors and Ki67 expression （P<0.05， P<0.01）， and significantly decreased contents of IL-6， IL-1β， and TNF-α in the serum （P<0.05， P<0.01）. Furthermore， administration of Guizhi Fulingwan markedly reduced MDSC infiltration in the spleen of the mice， with different degrees of increase in the levels of both CD4⁺ T and CD8⁺ T cells （P<0.05， P<0.01）， alongside significant decreases in the mRNA expressions of Arg1 and iNOS （P<0.05， P<0.01）. In vitro cell co-culture shows that administration of drug-containing serum of Guizhi Fulingwan significantly decreases the activity levels of ROS and iNOS in MDSCs and promotes the proliferation of CD8⁺ T cells and the secretion of GZMB and IFN-γ （P<0.05， P<0.01）. ConclusionGuizhi Fulingwan can reduce pro-inflammatory cytokine secretion and inhibit tumor proliferation in the colon tissues of CAC mice. Its potential mechanism may involve reducing MDSC infiltration， enhancing effector T cells， particularly CD8⁺ T cell response， and improving the tumor immunosuppressive microenvironment.

Objective: To investigate the incidence and influencing factors of new onset suicidal behaviors among junior and senior high school students, so as to provide evidence for early warning and intervention. Methods: Using a cluster sampling method, baseline data were collected from September to November 2023 among 2 379 adolescents selected from 2 junior high schools, 2 general senior high schools and 2 vocational senior high schools in Wuhan, Hubei Province, with follow up carried out from September to November 2024. Data were collected using the School Adaptation Scale, the Essential Resilience Scale, the Personal Social Support Scale, the Adverse Childhood Experiences Questionnaire, the Adolescent Life Events Scale, the Pittsburgh Sleep Quality Index, the Center for Epidemiologic Studies Depression Scale, and the Columbia-Suicide Severity Rating Scale. Multivariate Logistic regression analysis was used to identify factors influencing new onset suicidal behavior among junior and senior high school students. Results: Among junior and senior high school students without suicide risk at baseline, 53.55% remained stable risk free during follow up, while 13.28% developed new suicidal behavior during follow up, of which suicidal ideation, suicide plan and suicide attempts accounted for 11.69%, 8.83% and 6.52%, respectively. Multivariate Logistic regression revealed that increased depressive symptoms at follow up elevated the risk of overall new onset suicidal behaviors ( OR =4.14), ideation ( OR = 4.59), plans ( OR =4.24), and attempts ( OR =4.09); poor sleep quality also increased the risk of overall new onset suicidal behaviors ( OR =2.23), plans ( OR =2.03), and attempts ( OR =2.65) (all P <0.05). Non boarding junior and senior high school students had lower risks of overall new onset suicidal behaviors and ideation ( OR=0.70 and 0.49, respectively); secondary school students with academic performance ranking in the top 20%-30% of their class had a lower risk of new onset ideation ( OR =0.27); and those whose place of origin was outside the city had a lower risk of new onset plans ( OR =0.49) (all P <0.05). Conclusions New onset suicidal behaviors among junior and senior high school students exhibit dynamic and stage specific differences. Depressive symptoms serve as a common core risk factor across all stages, whereas sleep quality, academic performance, boarding status, and place of origin exert differential influences at distinct stages.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Objective: To explore the assocation of the family environment and depressive symptoms among primary and middle school students, so as to provide suggestions for further maximizing the utility of family environment in the growth of primary and secondary school students, as well as prevention and intervention of depressive symptoms among children and adolescents. Methods: From June to July 2024, through a multistage cluster random sampling method, 8 800 primary and middle school students aged 10 to 18 from 36 schools in 3 cities (Datong, Lvliang, Linfen) in Shanxi Province. A self designed questionnaire was used to conduct a family environment survey, including family socioeconomic conditions, family structure, family parenting behavior, family member health behavior, etc; and the depression symptoms of primary and secondary school students were investigated by Patient Health Questionnaire-9. The χ 2 test and binary Logistic regression to method were used to analyze the association of the family environment with depressive symptoms among primary and secondary school students, and to analyze gender and urban-rural heterogeneity in this association. Results: The detection rate of depressive symptoms among primary and middle school students was 46.7% ( n = 4 111 ). Among them, the detection rates of depressive symptoms for male and female students were 45.7% and 47.7% respectively, and the detection rates for rural and urban students were 48.0% and 44.9% respectively. The results of binary Logistic regression model showed that in the family environment, factors such as the father s education level (junior high school: OR =0.84), self assessed family socio economic status (average: OR =0.78, good: OR =0.80), parental support and understanding (yes: OR = 0.55 ), family atmosphere (harmonious: OR =0.66), living arrangement (living only with father or mother: OR =1.31, living with parents and grandparents: OR =1.19), and family rearing style (combining punishment and reward: OR =1.42, punishment only: OR =1.25) were related to depressive symptoms in primary and middle school students in Shanxi Province ( P <0.05). From the perspective of gender heterogeneity, the living arrangement (living only with father or mother: OR =1.67, others: OR =1.67) had a statistically significant association with depressive symptoms in male students ( P <0.05). From the perspective of urban rural heterogeneity, the living arrangement (living only with father or mother: OR =1.38) had a statistically significant association with depressive symptoms in rural primary and middle school students ( P <0.05). Conclusions The family environment has an important impact on depressive symptoms in primary and middle school students. Family functioning should be fully exerted to prevent depressive symptoms in primary and middle school students.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To explore the characteristics of fluid flow within loaded osteons under different boundary conditions.Methods The COMSOL Multiphysics software was used to establish a three-dimensional(3D)finite element model of osteons with different boundary conditions,and the variation rules of pore pressure and flow velocity of osteons under different inner wall pulsating blood pressures and outer wall elastic constraint conditions were analyzed.Results As the pulsatile blood pressure inside the osteon increased from 0 mmHg(1 mmHg=0.133 kPa)to 300 mmHg,the peak pore pressure within the osteon correspondingly increased from 26 kPa to 68 kPa.As the elastic constraint on the outer wall of osteons changed from being completely elastic to completely constrained,the peak pore pressure within osteons increased from 15 kPa to 26 kPa,and the peak flow velocity increased from 0.04 um/s to 0.07 um/s.Conclusions This study reveals the influence laws of changes in boundary conditions such as the pulsatile blood pressure on the inner wall and the elastic constraint on the outer wall of osteons on fluid flow characteristics within loaded osteons.These findings are conducive to a deeper understanding of the mechanical response mechanisms of bone tissues in both physiological and pathological states,and provide an important theoretical basrs for further researches on bone mechanotransduction.