ObjectiveTo explore the effect of modified Ditan Decoction （涤痰汤） on chronic intermittent hypoxia cognitive function and the potential function mechanism. MethodsTwenty-four Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， and a modified Ditan Decoction group， with eight rats in each group. Rats in the modified Ditan Decoction group were administered the decoction by gavage at 14.8 ml/（kg·d）， while the normal group and the model group received the same dose of normal saline. Thirty minutes after daily gavage， the rats in all three groups were placed in an intermittent hypoxia chamber. The oxygen concentration for the model group and the modified Ditan Decoction group was adjusted daily for 8 hours using a computer program to establish the model， while the normal group was exposed to the same airflow rate of ambient air. The intervention was continued for 12 weeks to establish a chronic intermittent hypoxia rat model. The Y-maze test was used to evaluate spatial working memory in the rats. Resting-state functional magnetic resonance imaging （rs-fMRI） was performed to detect whole-brain regional homogeneity （ReHo） and seed-based functional connectivity （FC）. Brain regions showing significant differences in rs-fMRI were selected for further analysis. Immunofluorescence was used to detect β-amyloid （Aβ） deposition and the number of ionized calcium-binding adapter molecule 1 （IBA1）-positive microglial cells. Immunohistochemistry was employed to assess the expression of synaptophysin （SYP）， the excitatory synapse marker vesicular glutamate transporter 1 （Vglut1）， and the inhibitory synapse marker vesicular γ-aminobutyric acid transporter （VGAT）. ResultsCompared with the normal group， the model group showed a reduced spontaneous alternation rate in the Y-maze test. The smoothed Z-score standardized regional homogeneity （SzReHo） value in the left entorhinal cortex significantly increased， and the FC value from this seed point to the left basal forebrain significantly reduced. Additionally， the model group exhibited significantly higher Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， decreased expression of SYP， Vglut1， and VGAT， along with an increased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. Compared to the model group， the modified Ditan Decoction group demonstrated an increased spontaneous alternation rate， a significantly reduced SzReHo value in the left entorhinal cortex， and a significantly increased FC value from this region to the left basal forebrain. Furthermore， this group showed significantly lower Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， increased levels of SYP， Vglut1， and VGAT， and a decreased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. ConclusionModified Ditan Decoction can reconstruct the projection from the left basal forebrain to the entorhinal cortex in chronic intermittent hypoxia， thereby reducing Aβ aggregation and excessive microglial activation in the left entorhinal cortex. This process improves the excitation/inhibition imbalance caused by synaptic remodeling， ultimately enhancing cognitive function in rats of chronic intermittent hypoxia.

AIM: To analyze the risk factors for recurrence after pterygium excision and the influence on corneal astigmatism and tear film break-up time.METHODS:Retrospective study. A total of 110 pterygium patients(110 eyes)admitted to our hospital from January 2020 to January 2023 were selected, including 77 primary pterygium patients(77 eyes)and 33 recurrent pterygium patients(33 eyes). Pterygium excision was performed in all patients. The corneal astigmatism and tear film break-up time of patients with pterygium were measured before and after operation. The recurrence of pterygium was analyzed and the risk factors of recurrence were analyzed.RESULTS:In this study, 8 eyes with pterygium recurred after excision, and the recurrence rate was 7.3%. There was no difference in corneal astigmatism of all patients before and after surgery(2.02±0.32 vs 2.00±0.32 D, P>0.05), and there was a difference in tear film break-up time(9.55±1.24 vs 13.46±2.56 s, P<0.05). The results of multi-factor Logistics regression analysis showed that age, working environment, diabetes, pterygium nature, postoperative tear film break-up time and operation method were the factors that affected the recurrence of pterygium after excision(all P<0.05).CONCLUSION:Age, working environment, diabetes mellitus, pterygium nature, postoperative tear film break-up time and surgical method are all risk factors for postoperative recurrence of pterygium.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

ObjectiveTo explore the mechanism by which the ethanol extract of Epimedium brevicornu （EEBM） intervenes in mesenchymal adipose-derived stem cells （ADSCs） to delay aging in castrated rats. MethodsForty-five 3-month-old SPF female SD rats were ovariectomized and randomly divided into model group， ADSCs treatment group， and ADSCs groups treated with low， medium， and high concentrations of EEBM （1， 50， 100 μg·L^-1）， referred to as the AE low， medium， and high concentration groups， with 9 rats in each group. After tail vein injection of 200 μL of the corresponding stem cell suspension， aging-related indicators including cyclin-dependent kinase inhibitor （p21）， tumor suppressor gene （p53）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， superoxide dismutase （SOD）， malondialdehyde （MDA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteine-aspartic acid protease-3 （Caspase-3）， and lipofuscin were measured using enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultsCompared with the model group， the IL-6 content in the AE low， medium， and high concentration groups was significantly decreased （P<0.05）. Lipofuscin， MDA， and IL-8 levels in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.01）， while SOD content was significantly increased （P<0.05， P<0.01）. Compared with the ADSCs treatment group， lipofuscin and IL-8 levels in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）. The MDA content was significantly decreased in the AE medium concentration group （P<0.01）. Compared with the model group， protein levels of p21， p53， Bax， and Caspase-3 in the ADSCs treatment group and AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， while the Bcl-2 protein level was significantly increased （P<0.01）. Compared with the ADSCs treatment group， protein levels of p21， p53， Bax， and Caspase-3 in the AE low， medium， and high concentration groups were significantly reduced （P<0.05， P<0.01）， and the Bcl-2 protein level in the AE low concentration group was significantly increased （P<0.01）. ConclusionThe results of this experiment show that EEBM-treated ADSCs or ADSCs may delay aging in castrated rats by inhibiting cell apoptosis， reducing cell cycle inhibitors and pro-inflammatory factors， enhancing antioxidant capacity， and reducing oxidative reactions. Moreover， EEBM-treated ADSCs demonstrate stronger anti-aging effects than ADSCs alone. This study provides experimental evidence supporting the clinical use of EEBM to intervene in ADSCs and delay aging.

ObjectiveTo establish fingerprint profiles and a quantitative determination method for Lycii Cortex， providing a scientific basis for the formulation of quality standards for Lycii Cortex and its roasted products. MethodsHigh performance liquid chromatography（HPLC） was developed for the quantitative method for determining kukoamine B in Lycii Cortex and its roasted products on an Alphasil XD-C₁₈ CH column（4.6 mm×250 mm， 5 μm）. HPLC fingerprint profiles were established for 10 batches of Lycii Cortex and its roasted products， and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the common peaks based on reference standards， literature and MS information. Quality evaluation indicators included yield of decoction pieces， appearance properties， content of kukoamine B， and fingerprint profiles. The temperature and time of the roasting process were investigated to select the optimal preparation process， which was then verified. Additionally， chemical pattern recognition was combined to assess the differences in the chemical composition of Lycii Cortex before and after roasting， as well as among samples from different origins. ResultsQuantitative analysis indicated that the contents of kukoamine B in Lycii Cortex and its roasted products were 0.35%-5.51% and 0.24%-4.15%， respectively. The transfer rate of kukoamine B was 58.6%-78.9% after roasting. The fingerprint profile analysis demonstrated that the method established in this study effectively separated kukoamine B from other components in the samples and distinctly differentiated it from its impurity peak， cis-N-caffeoylputrescine. The HPLC fingerprint profiles of Lycii Cortex and its roasted products showed high similarity（all above 0.95）， with 7 common peaks identified and five common components， including kukoamine B， cis-N-caffeoylputrescine， N-coumaroyl tyramine， feruloyltyramine， and glucosyringic acid， confirmed. Process optimization confirmed that baking at 110 ℃ for 20 min was a stable and feasible method for roasting Lycii Cortex. Principal component analysis and cluster analysis showed that there was little difference in the chemical composition between raw and roasted Lycii Cortex， but the quality of Lycii Cortex from different origins differed greatly. ConclusionThis study successfully established the fingerprint profiles and a quantitative method for the effective component kukoamine B in Lycii Cortex and roasted Lycii Cortex. The qualitative and quantitative analyses clarified that the impact of the roasting process on the chemical composition of Lycii Cortex was less significant than the variations due to its geographical origin. The findings of this study offer a reference for the development of quality evaluation methods and the establishment of quality standards for Lycii Cortex and its processed products.

Objective: To analyze the factors related to dual use of traditional cigarettes and e-cigarettes among middle school students in Beijing, in order to provide a scientific basis for adapting to the new situation and carrying out tobacco control among adolescents. Methods: A multi stage cluster random sampling method was used to select 15 688 and 13 607 junior and senior middle school students from 16 districts in Beijing from April to June in 2019 and 2023, respectively. Online self administered questionnaires among middle school students in Beijing were completed, including use of traditional cigarettes and e-cigarettes, exposure to second hand smoke, attitudes and perceptions towards tobacco, etc. The Chi-square test was used to compare rates, and a multiple factors Logistic regression model was used to analyze related factors of traditional cigarettes and e-cigarettes dual use among middle school students. Results: The dual use rate of traditional cigarettes and e-cigarettes in 2023 had decreased to 2.46% from 4.88% in 2019 among middle school students in Beijing. The results of the multiple Logistic regression model analysis showed that among middle school students, tobacco control anywhere at home (boys: OR =0.47, girls: OR =0.34), without anyone smoking on campus in the past month (boys: OR =0.43, girls: OR =0.26) had lower risks of dual use ( P <0.05); and middle school students strongly or slightly agreeing that smoking could bring happiness (boys: OR =4.11, 2.22, girls: OR =5.32, 3.87), believing that smoking could increase attractiveness of young people (boys: OR =3.13, girls: OR =5.81), smoking cigarettes handed over by good friends (boys: OR =4.24, girls: OR =7.21), thinking smoking in the next year (boys: OR =5.77, girls: OR =7.74) had higher risks of dual use ( P <0.05).Among boys, junior middle school students ( OR =0.50), excellent academic performance ( OR =0.36), no acceptance of free tobacco products from tobacco companies ( OR =0.38), believing that smoking couldn t refresh oneself ( OR =0.37) and smoking still could pose a health hazard though not yet addictive ( OR =0.32) had lower risks of dual use ( P <0.05);and boys with a history of secondhand smoke exposure indoor outside home ( OR =2.19), believing that quitting smoking without difficulty ( OR =2.57),smoking e-cigarettes handed over by good friends ( OR =11.27) had higher risks of dual use ( P <0.05). Among girls, no acceptance of using tobacco product labeled items ( OR =0.28) had lower risks of dual use ( P <0.05); and girls whose parents both smoke ( OR =5.53), believing that quitting smoking might not be difficult ( OR =4.44) had higher risks of dual use ( P < 0.05 ). Conclusions The dual use rate of traditional cigarettes and e-cigarettes among middle school students in Beijing has decreased. It is recommended to take the construction of smoke free families as the starting point, so as to reduce indoor second hand smoke exposure and control tobacco promotions, and promote the formation of correct tobacco control culture and moral constraints among secondary school students.

Objective To establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. Methods Patients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. Results A total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. Conclusion For patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.

[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

ObjectiveTo explore the mechanism by which modified Guishenwan alleviates inflammation in the rat model of polycystic ovary syndrome （PCOS） by regulating the mitogen-activated protein kinase （MAPK）/nuclear factor kappa B （NF-κB） pathway. MethodsAccording to the random number table method， 60 SPF female SD rats were randomized into a normal group （n=10） and a modeling group （n=50）. The normal group received routine feeding， while the modeling group was administrated with letrozole （1 mg·kg^-1·d^-1） by gavage for 21 days for the modeling of PCOS. The successfully modeled rats were randomized into model， diane-35 （0.2 g·kg^-1·d^-1）， high- （16.04 g·kg^-1·d^-1）， medium- （8.02 g·kg^-1·d^-1）， low- （4.01 g·kg^-1·d^-1） dose modified Guishenwan groups. The drug intervention groups were administrated with modified Guishenwan at corresponding doses by gavage， and the normal group and model group were given equal volumes of normal saline. All the groups were continuously treated for 28 days. After treatment， Gram staining of vaginal smears was employed to observe the estrous cycle in each group. Enzyme-linked immunosorbent assay was employed to determine the levels of follicle-stimulating hormone （FSH）， estradiol （E₂）， luteinizing hormone （LH）， testosterone （T）， and progesterone （PROG） in the plasma， as well as interleukin-1 beta （IL-1β）， tumor necrosis factor-alpha （TNF-α）， and interleukin-10 （IL-10） in the plasma and ovarian tissue. The LH/FSH ratio was calculated. The morphological changes in the ovarian tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the protein levels of extracellular-regulated protein kinase （ERK）， c-Jun N-terminal kinase （JNK）， p38 MAPK， NF-κB p65， IκBα， p-JNK， p-ERK， p-p38 MAPK， p-NF-κB p65， and p-IκBα in the ovarian tissue. Real-time quantitative polymerase chain reaction was used to determine the mRNA levels of ERK， JNK， p38 MAPK， NF-κB p65， and IκBα in the ovarian tissue. ResultsCompared with the normal group， the model group was in the estrus phase， with an increase in the number of ovarian vesicles and decreases in granulosa cells and corpus luteum formation （P<0.05）， and lowered levels of FSH and E₂ and elevated levels of LH， T， and LH/FSH in the plasma （P<0.05）. Compared with the model group， high-， medium-， and low-dose modified Guishenwan recovered the estrous cycle， increased the generation of granulosa cells and corpus luteum， reduced the number of vesicles， elevated the levels of FSH and E₂， and lowered the levels LH， T， and LH/FSH （P<0.05， P<0.01） in a dose-dependent manner. High-dose modified Guishenwan demonstrated the best therapeutic effect. Therefore， subsequent experiments for exploring the treatment mechanism were conducted in the normal group， model group， and high-dose modified Guishenwan group. The results showed that compared with the model group， high-dose modified Guishenwan lowered the levels of IL-1β， TNF-α， and IL-10 and elevated the level of IL-10 in the plasma and ovarian tissue （P<0.05， P<0.01）， down-regulated the protein levels of p-ERK， p-JNK， p-p38 MAPK， p-NF-κB p65， and p-IκBα， while up-regulating the protein level of IκBα （P<0.01）. At the same time， the mRNA levels of ERK， JNK， p38 MAPK， and NF-κB p65 in the high-dose modified Guishenwan group were down-regulated （P<0.05， P<0.01）. ConclusionModified Guishenwan can improve the ovarian function in rat model of PCOS induced by letrozole and has anti-inflammatory effects， which may be related to inhibition of the MAPK/NF-κB pathway.

ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， the chemical constituents of Qili Qiangxin capsules was identified， and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules， as well as the serum， brain， heart， lung， spleen， liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software， the compound information database was constructed， and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time， accurate relative molecular mass and fragments， the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds， including 70 terpenoids， 60 flavonoids， 23 organic acids， 17 alkaloids， 20 steroids， 7 coumarins and 36 others， were identified or predicted from Qili Qiangxin capsules， 73 of which were identified matching with standard substances. Tissue distribution results showed that 71， 17， 38， 33， 32， 58 and 43 migrating components were detected in blood， brain， heart， lung， spleen， liver and kidney， respectively. Thirty-seven components were absorbed into the blood and heart， including quinic acid， benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues， including calycosin， methylnissolin， formononetin， alisol B， alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them， astragaloside Ⅳ， salvianolic acid B， ginsenoside Rb₁， ginsenoside Rb₃， ginsenoside Rd， ginsenoside Rg₃， calycosin-7-glucoside， and sinapine may be the important components for the treatment of heart failure， which can provide useful reference for its quality control and research on pharmacodynamic material basis.