[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。

OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

ObjectiveTo explore the possible mechanism of Jianpi Huazhuo Tiaozhi Granule （健脾化浊调脂颗粒， JHTG） in treating atherosclerosis （AS） based on the regulation of perivascular adipose tissue （PVAT） browning via the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway. MethodsFifteen SPF male C57BL/6J mice served as control group， while 76 ApoE^-/- mice were first fed a high-fat diet for 16 weeks to establish AS model. After successful modeling， they were randomly divided into model group （n=16）， as well as the browning group， the low-， medium- and high-dose JHTG group， with 15 mice in each group. The browning group was intraperitoneally injected with β3-adrenergic receptor agonist CL 316243 at 1 mg/（kg·d） once daily. The low-， medium- and high-dose JHTG groups were treated with 4.3 g/（kg·d）， 8.6 g/（kg·d）， and 17.2 g/（kg·d） of JHTG by gavage， respectively， while the control group and the model group were given normal saline at 10 ml/（kg·d） by intragastric administration， once daily. All groups received continuous intervention for 4 weeks. The aorta was collected to assess the plaque ratio by gross oil red O staining. HE staining was used to measure the plaque area in cross-sections. Masson staining was employed to detect the proportion of collagen fibers in plaque. Transmission electron microscopy was used to observe the quantity and morphological changes of mitochondria and lipid droplets in adipocytes. The levels of serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected， as well as tumor necrosis factor α （TNF-α） and interleukin 6 （IL-6） levels in the PVAT and aorta. The protein levels of adiponectin and leptin in PVAT， and protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated phosphoinositide 3-kinase （p-PI3K）， protein kinase B （AKT）， phosphorylated protein kinase B （p-AKT）， uncoupling protein 1 （UCP1）， peroxisome proliferator-activated receptor γ coactivator 1α （PGC-1α）， and PR domain containing 16 （PRDM16） were measured. The mRNA expression levels of UCP1， PGC-1α and PRDM16 in PVAT were detected. ResultsCompared to the control group， the model group showed increased serum TG， TC， and LDL-C levels and decreased HDL-C level， elevated TNF-α and IL-6 levels in PVAT and aorta， decreased average fluorescence intensity of adiponectin， increased average fluorescence intensity of leptin， reduced p-PI3K/PI3K and p-AKT/AKT values as well as protein levels and mRNA expression levels of UCP1， PGC-1α and PRDM16 （P＜0.01）. The pathological results showed that no significant plaque formation was observed in the aortas of mice in the control group. In the model group， multiple plaques were observed in the aortas， with large numbers of foam cells， cholesterol crystals， and inflammatory cell aggregation in the plaques. Compared to the model group， the browning group and the high-dose JHTG group significantly improved the above indicators and aortic pathological changes （P＜0.05 or P＜0.01）. Three JHTG groups showed a dose-dependent effect in reducing LDL-C level and plaque ratio by gross oil red O staining， elevating the average fluorescence intensity of adiponectin， the p-AKT/AKT value， the protein level of PGC-1α， and the mRNA expression levels of UCP1 and PRDM16 （P＜0.05）. The high-dose JHTG group and the browning group showed similar efficacy in improving the pathology of the aorta. ConclusionJHTG may promote PVAT browning in AS model mice through the PI3K/AKT pathway， improve the endocrine function of PVAT， inhibit aortic inflammation， and thereby ameliorate the formation of AS plaques.

AIM: To explore the effect of Kappa angle on changes in visual quality and stereoscopic acuity after regional refractive multifocal intraocular lens(MIOL)implantation in patients with high myopia complicated by cataract.METHODS:A retrospective analysis was conducted on data from patients with normal Kappa angle and high myopia complicated by cataract treated at the hospital from January 2024 to January 2025. Patients were divided into two groups based on the median preoperative Kappa angle(0.182 mm): Group A(00.05). The actual residual astigmatism in Group A was lower than that in Group B at 7 d, 1 and 3 mo postoperatively(all P<0.001). The proportion of eyes with near stereoscopic acuity <60″ was higher in Group A than in Group B, while the proportion of eyes with near stereoscopic acuity between 400″ and 3000″ was lower in Group A than in Group B(both P<0.05). Meanwhile, the incidence of visual disturbances in Group B was higher than that in Group A(P<0.05).CONCLUSION: The Kappa angle has no significant effect on visual acuity or objective visual quality in patients with normal Kappa angle and high myopia complicated by cataract after regional refractive MIOL implantation. However, patients with a larger Kappa angle exhibit higher postoperative residual astigmatism, worse near stereoscopic acuity, and a higher incidence of vision-related adverse symptoms.

OBJECTIVE To investigate the mechanism of Qushi huoxue decoction in improving metabolic-associated fatty liver disease （MAFLD） based on the AMP-activated protein kinase/mammalian target of rapamycin/UNC-51-like kinase 1 （AMPK/mTOR/ULK1） autophagy signaling pathway.METHODS Male C57BL/6J mice were randomly divided into normal group， model group， and low-， medium-， and high-dose Qushi huoxue decoction groups [4.10， 8.20， 16.40 mg/（g·d）]， with 10 mice in each group. Except for the normal group， mice in the other groups were fed a high-fat diet for 12 weeks to establish the MAFLD model. Starting 24 hours after modeling， mice in each group were administered the drug solution or normal saline once daily for 6 consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， alanine transaminase （ALT）， aspartate transferase （AST）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected according to the kit instructions. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe pathological changes in mouse liver tissue. Western blot and immunofluorescence staining were used to detect the expression and positive protein expression related to the AMPK/mTOR/ULK1 autophagy signaling pathway.RESULTS Compared with the normal group， the serum levels of TC， TG， ALT， AST， and LDL-C in the model group were significantly increased， while the HDL-C level was significantly decreased （ P ＜0.01）. HE staining showed obvious steatosis in hepatocytes of the model group， and oil red O staining showed a large amount of lipid droplet accumulation in liver tissue. Western blot and immunofluorescence staining results showed that the expression levels of p-mTOR/mTOR and p62 proteins， as well as the relative fluorescence intensities of p-mTOR and p62 proteins in liver tissue of the model group， were significantly increased/enhanced （ P ＜0.01）， while the expression levels of p-AMPK/AMPK， ULK1， and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） proteins， as well as the relative fluorescence intensities of p-AMPK and LC3 proteins， were significantly decreased/weakened （ P ＜0.01）. After intervention with Qushi huoxue decoction， the above pathological changes and abnormal indicators in liver tissue of mice in the low-， medium-， and high-dose groups were significantly reversed， with most indicators showing statistically significant differences （ P ＜0.05 or P ＜0.01）.CONCLUSIONS Qushi huoxue decoction can significantly improve liver pathology， blood lipid levels， and liver function in MAFLD model mice； this improvement may be achieved through the activation of the AMPK/mTOR/ULK1 autophagy signaling pathway.

TCM monomer and its compound preparation have significant effect in the treatment of breast cancer, with unique advantages of multi molecule, multi targeting, less adverse reactions, etc. TCM components such as Carthamus tinctorius polysaccharides, peimine, andrographolide, and Bupleurum saponin D can inhibit the malignant progression of breast cancer by modulating signaling pathways including PI3K/Akt, MAPK, Wnt, and JAK/STAT.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.

Objective To observe the clinical efficacy of therapy focusing on regulating spleen and stomach for the treatment of acoustic hypersensitivity(AH),which also named as auditory hyperaesthesia,and to explore the relevant factors influencing the efficacy.Methods From January 2018 to December 2023,the patients admitted to the outpatient department of otolaryngology-head and neck surgery of the First Affiliated Hospital of Guangzhou University of Chinese Medicine and diagnosed as AH with complete medical data were included as study subjects.Follow-up through telephone or network was carried out for those patients who with uncertain prognosis.The changes in the pre-and post-treatment scores of Indicators of Acoustic Hypersensitivity Severity(IAHS)were used as the reference index for efficacy evaluation,and the cure rate and effective rate were used as the efficacy analysis indexes for statistical analysis.And then the efficacy of traditional Chinese medicine(TCM)medical care combined with health care focusing on regulating spleen and stomach for the treatment of AH was evaluated.Furthermore,multivariate logistic regression was used to explore the relevant factors influencing the efficacy of AH.Results A total of 298 cases of AH patients meeting the inclusion criteria were collected,among which 151 cases(50.67%)were cured,22 cases(7.38%)were markedly effective,75 cases(25.17%)were effective,and 50 cases(16.78%)were ineffective,with a total effective rate of 83.22%(248/298).The univariate analysis results showed that eight factors(including post-treatment lifestyle score,range of lifestyle adjustment,severity of AH,duration of the disease,presence of tinnitus,presence of hearing drop,presence of vertigo,and age)had an influence on the efficacy,and the differences were statistically significant(P<0.05 or P<0.01).However,the factors of gender,occupation,education level,and history of noise exposure had no influence on the efficacy(P>0.05).The multivariate binary logistic regression analysis showed that five factors,namely post-treatment lifestyle score,range of lifestyle adjustment,severity of AH,presence of vertigo and duration of the disease,had a significant correlation with the cure rate of AH(P<0.05 or P<0.01),and four factors,namely post-treatment lifestyle score,severity of AH,range of lifestyle adjustment and age,had a significant correlation with the effective rate of AH(P<0.05 or P<0.01).Conclusion The method of TCM medical care and health care focusing on regulating spleen and stomach exerts a better efficacy for AH patients.And the lifestyle,severity of AH,duration of the disease,age,and presence of vertigo are the relevant factors affecting the outcomes,which is worthy of further in-depth study.

Tinnitus is a refractory condition in otology.It is widely accepted that patients with tinnitus can only adapt to it,for there is no universally recognized effective pharmacotherapy till now.Through the interpretation of classical Chinese medical texts and after decades of clinical practice,Professor Liu Peng proposes that the primary pathogenesis of tinnitus is due to spleen-stomach dysfunction,largely caused by unhealthy life styles.Based on the holistic perspective of traditional Chinese medicine(TCM),he developed the Yishi therapy for tinnitus management.Yishi therapy emphasizes the integration of medical treatment and self-care via prioritizing mentorship and assisting with medical techniques.The mentorship is embodied by identifying and correcting patients' unhealthy living habits,guiding the patients to maintain dietary moderation,regular living,and emotional regulation,thereby activating their self-recuperative powers and promoting tinnitus.Medical techniques refer to the utilization of oral use of herbal medicine and external therapies on the basis of adjustment of lifestyle,aiming to restore the spleen-stomach function of ascending of lucidity and descending of turbidity,thereby alleviating tinnitus.Oral use of herbal medicine is performed with Guzhong Decoction(mainly composed of Astragali Radix,Codonopsis Radix,Cinnamomi Ramulus,Zingiberis Rhizoma,Atractylodis Macrocephalae Rhizoma,Pinelliae Rhizoma Praeparatum,Amomi Fructus,Acori Tatarinowii Rhizoma,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle)as the basic formula,through modified use based on syndrome differentiation.External treatment mainly refers to auricular acupoint pressing and occipital-knocking therapy.By combining the medical treatment and self-care,Yishi therapy exerts reliable efficacy for the treatment of tinnitus through regulating spleen-stomach function and activating the self-recuperative powers,and will provide a novel therapeutic approach to tinnitus.