[摘 要] 目的：探讨胃肝样腺癌（HAS）的临床病理特征与免疫微环境异质性，筛选预后标志物，阐释其高侵袭性与疗效差的机制，为精准诊疗策略提供理论依据。方法:​​ 回顾性收集2013年1月至2025年5月期间海军军医大学第一附属医院与第二附属医院收治的65例HAS患者的临床信息及病理资料。采用免疫组织化学技术检测HAS​​肝样分化标志物、神经内分泌标志物​​等分子表达情况，通过Kaplan-Meier生存分析法明确与预后相关的靶点。利用多色免疫荧光技术鉴定肿瘤区域内免疫细胞亚群分布情况，以阐明其免疫微环境特征。结果：65例患者中，男性54例（83.1%），女性11例（16.9%），中位年龄68岁。肿瘤好发于贲门（40%），其次为胃窦（32.3%）和胃体（27.7%）。中位随访时间23.18个月，15例患者死亡，46例生存，4例失访。HAS的胃镜及手术标本大体观呈灰白色实性质硬肿物，镜下可见中低分化胃腺癌与肝细胞癌（HCC）样分化区交错分布。表达神经内分泌相关分子的HAS患者呈现出更多的淋巴结转移数量及更短的总生存期。免疫微环境解析显示，HAS总体缺乏免疫细胞浸润，呈现“冷肿瘤”特征；免疫细胞主要聚集于胃癌腺体周围区域，而在HCC样分化区域罕见淋巴细胞浸润。结论：HAS侵袭性强，根治性手术是主要治疗手段；神经内分泌转化提示不良预后，是个体化治疗的关键标志；免疫细胞浸润缺乏，可能是其免疫治疗响应不佳的原因。

The rabies virus(RABV)that causes rabies mainly attacks the peripheral and central nervous systems.In the later stages of infection,it is scattered in the salivary glands and transmit-ted to other susceptible animals through infectious saliva.To study dispersion of the RABV in the three pairs of salivary gland tissues,the street strain PB4 of the RABV was inoculated into 21-day-old female mice through the hind limb muscles.During the moribund stage of the mice,the sublin-gual gland,submandibular gland and parotid gland were collected,respectively.The TCID50 titer of RABV in the three kinds of glands of the mice and the copy number of the RABV N gene were de-tected,and RABV in different salivary glands was observed by immunofluorescence.The results showed that PB4 was dispersed in all three kinds of salivary glands of the mice,with the largest a-mounts in the parotid gland,followed by the submandibular gland,and the lowest amount in the sublingual gland.Three-month-old dogs were inoculated with PB4 through the cranial cavity,and saliva were collected every 12 h after inoculation.The saliva samples were detected by TCID50 and RT-qPCR.And during the moribund stage of the dogs when the disease occurred,the three pairs of salivary glands were collected.Through the determination of the TCID50 titer,RT-qPCR and immu-nofluorescence detection,it was demonstrated that among the three different salivary glands of the dogs,the largest amount of PB4 was found in the parotid gland and the lowest in the sublingual gland.Our results in mice and dogs clearly proved that the parotid gland was consistently found to exhibit the highest content of street RABV among the three major salivary glands,which could en-rich experimental data for analyzing the dispersion of RABV in the salivary glands and interpreta-tion of the intermittent secretion of saliva in clinically rabid dogs.

AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.

Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

Objective:To analyze the epidemiological characteristics of respiratory syncytial virus (RSV) infections in hospitalized children under five years of age with acute respiratory infections in Qingdao, China, from 2023 to 2025.Methods:This cross-sectional study enrolled children under five years hospitalized with acute respiratory infections between May 1, 2023, and June 30, 2025. Nucleic acid testing was performed for six respiratory pathogens. Participants were stratified into seven age groups: 0 to 28 days, 29 days to <6 months, 6 to <12 months, 1 to <2 years, 2 to <3 years, 3 to <4 years, and 4 to <5 years. Intergroup differences were analyzed using Chi-square tests, with Bonferroni correction (adjusted α=0.016 7) for peak rate comparisons across three epidemic seasons. Results:Among 16 613 children, RSV was detected in 3 280 cases (19.74%), representing the highest pathogen detection rate. Infants under one year accounted for 56.37% (1 849/3 280) of RSV-positive cases, with significantly higher positivity rates in the 0-28 days [25.22% (286/1 134)], 29 days to <6 months [26.66% (1 072/4 021)], and 6 to <12 months [24.92% (491/1 970)] groups compared to other age groups ( χ2=314.20, P<0.001). Co-infections occurred in 13.66% (448/3 280) of RSV-positive cases, primarily with rhinovirus (6.13%, 201/ 3 280), followed by adenovirus and Mycoplasma pneumoniae (3.35% each, 110/3 280). Epidemiological surveillance revealed an off-season outbreak from May to July 2023 (duration ≥14 weeks, peak positivity rate 71.15%), while both 2024 (20 weeks, peak 52.55%) and 2025 (24 weeks, peak 46.49%) exhibited typical winter-spring seasonal patterns. The 2023 peak rate significantly exceeded those of subsequent years (all pairwise P<0.016 7). Conclusion:RSV is the predominant pathogen among hospitalized children under five years with acute respiratory infections in Qingdao, with infants under one year representing the highest-risk population. The epidemiological pattern demonstrates a transition from post-pandemic off-season outbreaks to prolonged winter-spring epidemics, highlighting the need for continued surveillance and targeted prevention strategies.

Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

AIM:To investigated the mechanism of action of Yiqi tongfu xiere prescription(YTX)in treating mice with lipopolysaccharide(LPS)-in-duced acute lung injury(ALI).METHODS:According to the random number table,24 C57BL/6 mice were divided into 4 groups:control group(Control),model group(LPS),low dose group(YTX-L)and high dose group(YTX-H).Except for the control group,the mice models of acute lung injury were established by intratracheal instillation of LPS solu-tion(5 mg/kg).The low and high dose treatment groups were given intragastric administration con-tinuously for 14 days.After 24 hours,the lung tis-sue,bronchoalveolar lavage fluid(BALF)and serum of the four groups were taken for follow-up detec-tion.The degree of pulmonary edema was evaluat-ed by wet weight coefficient(wet to dry ratio,W/D)of lung tissue.The degree of alveolar inflamma-tion and pulmonary fibrosis were evaluated by HE and Masson staining,and the contents of BALF and serum inflammatory cytokines IL-1β and IL-6 were detected by ELISA.The protein expressions of α-SMA,FN,Col-Ⅰ and Col-Ⅲ were measured by West-ern blot.Determination of α-SMA,FN,Col-Ⅰ,MAPK,NF-κB mRNA expression by RT-PCR method.RE-SULTS:Compared with LPS group,the contents of BALF,IL-1β and IL-6 in serum,Wmax D ratio,lung pathology,serum α-SMA,FN,Col-Ⅰ,Col-Ⅲ protein expression and α-SMA,FN,Col-Ⅰ,MAPK,NF-κB mRNA expression in treatment group were signifi-cantly lower than those in control group.CONCLU-SION:YTX can significantly reduce the levels of pul-monary fibrosis markers such as α-SMA,FN,Col-Ⅰand Col-Ⅲ by inhibiting the activation of MAPK/NF-κB signal pathway,and improve alveolar inflamma-tion and pulmonary fibrosis in mice with lung inju-ry,suggesting that YTX can treat acute lung injury and provide a theoretical basis for the clinical use of YTX.

Objective Based on a clinical cohort study of repeated ketamine infusions for treatment-resistant depression(TRD),this study aimed to examine differences in brain-derived neurotrophic factor(BDNF)methylation among patients with varying therapeutic responses and explore its potential role in predicting treatment efficacy.Methods A retrospective analysis was conducted on peripheral plasma BDNF levels in 83 patients with TRD before and after a 2-week course of ketamine treatment(6 injections total).The Montgomery-Asberg depression rating scale(MADRS)was used to assess treatment efficacy.BDNF methylation levels were compared between responder group and non-responder group.The effect of methylation of the target CpG site on transcriptional activity was verified by using the dual luciferase reporter gene system.Results In patients with TRD who completed six repeated ketamine infusions,the responder group showed significant improvements compared to baseline levels in both MADRS scores(25.20±7.54 vs.8.10±5.32,P<0.01)and plasma BDNF concentrations[8.74(5.26,13.46)ng/mL vs.16.59(7.41,24.46)ng/mL,P<0.01].At baseline,35 CpG sites within the BDNF gene displayed significant methylation differences between response groups(P<0.05).Two CpG sites(rs1240718851 and cg06260077)located in the BDNF promoter region demonstrated a hypermethylation-low expression correlation,and dual-luciferase reporter assays confirmed that one of these sites functionally modulates BDNF expression.Conclusions The plasma BDNF concentration in TRD patients increases with the remission of depressive symptoms.The regulation of BDNF gene expression by methylation can predict the antidepressant efficacy of repeated intravenous ketamine.

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

AIM:To elucidate the intervention and mechanism of 4'-hydroxychalcone(4-HC)in colitis mice through the regulation of Th17/Treg homeostasis.METHODS:Using a dextran sodium sulfate(DSS)-induced colitis model in mice,we meticulously observed the pathological characteristics of colon tissue via HE staining.Additionally,we employed immunohistochemical analysis and Western blot techniques to assess the expression levels of proteins associated with the JAK/STAT signaling pathway,as well as the specific content of tight junction proteins such as ZO-1 and occludin.The differentiation of Th17 and Treg cells was analyzed through flow cytometry.RESULTS:Compared to the normal group,the DSS group exhibited a consistent decline in body weight,coupled with symptoms of diarrhea and hematochezia,an increase in the DAI score,and a notable reduction in colon length.In contrast,the body weight of the 4-HC group dis-played an upward trend following an initial decrease,with improvements in diarrhea and hematochezia symptoms,a reduc-tion in the DAI score,and a restoration of colon length relative to the model group.The integrity of colon tissue in the 4-HC group was significantly better than that in the DSS group,evidenced by a marked increase in the number of goblet cells and an enhancement in crypt integrity,while the average histology score showed a decrease.Western blot analysis re-vealed substantial increase in ZO-1 and occludin expression after 4-HC treatment.Flow cytometry results indicated a dra-matic decrease in the differentiation rate of Th17 cells in spleen lymphocytes and mesenteric lymph nodes,while the dif-ferentiation rate of Treg cells was significantly elevated.Immunohistochemical and Western blot analyses demonstrated that 4-HC markedly reduced the phosphorylation of STAT1 and STAT3,while up-regulating the phosphorylation of STAT6,suggesting that 4-HC modulates CD4+T cell activity through the JAK-STAT pathway.CONCLUSION:The 4-HC may enhance the course of DSS-induced colitis in mice,alleviate colonic tissue damage,and modulate the balance be-tween Th17 and Treg cells,potentially involving the JAK/STAT signaling pathway.