OBJECTIVE To investigate the mechanism by which the traditional Chinese medicine formula Xibining Ⅱ modulates cold-stimulus pain sensitivity in rats with cold-damp obstruction-type knee osteoarthritis （KOA） based on the SET domain bifurcated histone lysine methyltransferase 2 （SETDB2）/histone H3 lysine 9 trimethylation （H3K9me3） signaling axis. METHODS Fifty SD rats were randomly divided into control group （intragastric administration and intrathecal injection of equal volumes of normal saline）， model group （intragastric administration and intrathecal injection of equal volumes of normal saline）， Xibining Ⅱ low- and high-dose groups （4， 8 g/kg Xibining Ⅱ， intragastric administration）， and high-dose of Xibining Ⅱ+small interfering RNA （siRNA） group （8 g/kg of Xibining Ⅱ via intragastric administration and intrathecal injection of SETDB2 siRNA at 0.2 mmol/L， 20 μL per rat）， with 10 rats in each group. Except for the control group， cold-damp obstruction-type KOA model was induced in other groups. Drug administration commenced 14 days post-modeling and continued for 28 days. Following the final administration， the following were assessed： behavioral changes in cold-stimulation pain sensitivity， histopathological changes in the articular cartilage of the knee joint， the contents of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）] and pain mediators [calcitonin gene-related peptide （CGRP）， nerve growth factor （NGF）]， as well as the expressions of SETDB2/H3K9me3 signaling axis，inflammatory factors and pain mediators related proteins and mRNAs in dorsal root ganglion （DRG） tissue. RESULTS After 28 days of drug administration， compared with the model group， Xibining Ⅱ low- and high-dose groups exhibited significantly prolonged cold-stimulus paw withdrawal latency （P＜0.05）； the number of positive responses in the acetone low-temperature test was significantly reduced （P＜0.05）； Mankin score and the Osteoarthritis Research Society International score for knee joint tissue， as well as the levels of inflammatory factors and pain mediators in the serum and their expression in DRG tissue were all significantly decreased （P＜0.05）； the protein expressions of SETDB2 and H3K9me3 in DRG tissue were significantly increased （P＜0.05）. Intrathecal injection of SETDB2 siRNA reversed the above effects of high-dose of Xibining Ⅱ （P＜0.05）. CONCLUSIONS Xibining Ⅱ may alleviate inflammatory and pain responses by activating the SETDB2/H3K9me3 signaling axis， ultimately improving cold-stimulus pain sensitivity in rats with cold-damp obstruction-type KOA.

Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

Objective: To explore the association between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms among first year junior high school students in Yunnan Province, so as to provide theoretical basis for the prevention of anxiety and depressive symptoms co-occurrence among adolescents. Methods: A random cluster sampling involving 8 500 first year junior high school students in 11 counties in Yunnan Province was conducted by a questionnaire survey from October to December 2022. The Depression Anxiety Stress Scale-21 (DASS-21) was applied to assess anxiety and depressive symptoms in first year junior high school students. Chi-square test was used to compare the anxiety-depression co-occurrence symptoms of first year junior high school students with different demographic characteristics. The association between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms of adolescents was analyzed by binary Logistic regression models. Results: The detection rate of co-occurrence of anxiety and depression symptoms among first year junior high school students in Yunnan Province was 26.92%. After controlling for demographic variables and other confounders, takeout fast foods and sugar sweetened beverage consumption( OR=1.50, 95%CI =1.27-1.77) was associated with anxiety-depression co-occurrence symptoms among first year junior high school students in Yunnan Province ( P <0.01). Stratified analysis showed that both Han ( OR=1.37, 95%CI =1.07-1.77) and ethnic minorities ( OR=1.60, 95%CI =1.29-2.00) exhibited statistically significant associations between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms(both P <0.05). Conclusions Takeout fast foods and sugar sweetened beverage consumption increases the risk of co-occurrence of anxiety and depressive symptoms among first year junior high school students in Yunnan Province. It is recommended to strengthen guidance on the consumption of such products among junior high school students to prevent co-occurrence of anxiety and depressive symptoms.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Background Both productive dust and noise are occupational hazards, and each can induce changes in blood glucose levels among workers. Objective To explore the potential interactive effects of exposure to productive dust and noise on the risk of hyperglycemia among automobile manufacturing workers. Methods Using a cluster sampling method, workers undergoing occupational health examination from three automobile manufacturing plants in Wuhan in 2022 were selected. Basic information was collected using a questionnaire designed by the Chinese Center for Disease Control and Prevention. Exposure history was obtained through occupational history interviews. Clinic indicators such as blood pressure, blood lipids, fasting blood glucose (FBG), and fatty liver status, were retrieved from examination records. Hyperglycemia was defined as FBG > 6.1 mmol·L^-1. Logistic regression models analyzed the independent effects of occupational noise and dust exposure, while additive and multiplicative interaction models assessed their interactive effects on hyperglycemia. Results The prevalence of hyperglycemia among the 1223 participants was 7.7%. Logistic regression showed that using workers without exposure as reference, the odds ratios (OR) and 95% confidence intervals (CI) for hyperglycemia among workers exposed only to dust, only to noise, and to both were 2.15 (1.90, 4.23), 2.23 (1.40, 5.08), and 3.75 (1.95, 7.24), respectively. A linear association was observed between the duration of noise exposure and blood glucose levels (P<0.05). Interaction analysis showed no multiplicative interaction or additive interaction. Conclusion Exposure to productive dust and noise are independent risk factors for hyperglycemia among workers. While both contribute to increased risk, no significant synergistic interaction is observed.

"Pattern identification by formula" originates from the formula-pattern correspondence theory in traditional Chinese medicine （TCM）， with its core being the reverse inference of the pattern attributes of models through pharmacodynamic responses after formula intervention. With the advancement of TCM modernization， stable and reliable pattern models have become an important bridge connecting basic research and clinical practice， and "pattern identification by formula" has provided a feasible approach to enhance the authenticity and clinical translational value of these models. In recent years， notable progress has been achieved in its application to single-pattern models （such as phlegm-stasis pattern， Yang deficiency pattern， and spleen-Qi deficiency pattern） as well as disease-pattern combination models involving the respiratory， digestive， circulatory， and nervous systems. It has not only verified the pattern attributes of the models but also revealed the pattern differentiation regularity of "different diseases with the same pattern" and "the same pattern treated with different formulas". On this basis， this study further conducts a commonality analysis of pattern models， summarizes them into two major categories （deficiency patterns and excess patterns）， and embodies the pathological connotation of "deficiency results from essence-Qi consumption， and excess arises from pathogen abundance". This not only reveals the internal connections between different models but also provides a basis for the summary of formula-pattern rules and research on pattern standardization. However， current studies still suffer multiple problems such as non-standardized naming of patterns， lack of rationality in modeling methods， simplified design of control experiments， and insufficient description of macroscopic patterns in evaluation indicators， which affect the scientific rigor and reproducibility of the research. Future research needs to promote the unification of nomenclature and evaluation criteria of patterns， optimize modeling methods， strengthen the design of control experiments， and establish a multi-dimensional model evaluation system integrating macro- and micro-level indicators. This aims to improve the rigor and strength of evidence for "pattern identification by formula" studies， strengthen interdisciplinary integration and clinical feedback， and promote the development of TCM pattern models towards standardization and scientification. This study not only provides theoretical reference and methodological support for improving the system of TCM pattern animal models but also offers an important pathway for the experimental interpretation and modernization of TCM theories.

In recent years, with the improvement of people's awareness of physical examination and the more accurate detection equipment, the detection rate of pulmonary nodules is getting higher and higher. Surgical resection is the first choice for the treatment of malignant pulmonary nodules, but multiple pulmonary nodules, nodules in complex areas and those with surgical contraindications are not suitable for surgery. As an effective, less invasive and low-cost treatment, ablation has developed rapidly in the treatment of multiple pulmonary nodules. This article introduces the progress of several common ablation techniques (radiofrequency ablation, microwave ablation, cryoablation) in the treatment of multiple pulmonary nodules, the indications and contraindications of ablation techniques, the efficacy evaluation and complications after ablation therapy, and the prospects of ablation techniques in the treatment of multiple pulmonary nodules.

ObjectiveTo carry out a health technology assessment （HTA） of acupuncture for secondary dysmenorrhea （SD） caused by adenomyosis and endometriosis， in order to provide a reference for relevant medical decision-making. MethodsFrom the perspective of the health system， the assessment covers seven areas， including the technical characteristics， safety， effectiveness， economics， ethical fairness， organizational adaptability， and impact on patients and society. The results are reported accordingly. ResultsThe operational specifications of acupuncture are standardized， and the conditions for its use are clearly defined. Acupuncture has a lower overall incidence of adverse events. The main adverse events are localized pain， subcutaneous bleeding， and dizziness， with most symptoms being mild， all of which have corresponding standard treatments. No reports on occupational or environmental safety were found， and the safety operation specifications are available for reference. Compared with conventional Western medicine， acupuncture demonstrates higher effectiveness. Acupuncture may improve the quality of life scores of patients， though no significant difference was observed. The cost of acupuncture is higher than that of conventional Western medicine， but its overall economic value is greater. The informed consent information is relatively comprehensive. Most patients are aware of the potential benefits and risks of acupuncture and voluntarily opt for it. The treatment process fully respects patient privacy and human rights. The clinical application of acupuncture follows the current acupuncture medical service model， with no special requirements for the level of medical institutions. Patient accessibility and affordability are suitable. Patient satisfaction is high. Most patients indicated they would choose acupuncture again for SD. The main barriers to choosing acupuncture are psychological factors （such as fear of acupuncture）， cost， and transportation issues. Nearly 70% of patients receiving acupuncture treatment benefit from medical insurance reimbursement， with reimbursement rates generally above 50%， indicating strong social security support. ConclusionThe implementation of HTA for acupuncture in the treatment of SD， using the standards for traditional Chinese medicine （TCM）， is feasible. The implementation steps are clear， the data sources for each evaluation domain are adequate， the analysis methods are practical， and the evaluation results are comprehensive. Experts recommend that the findings be used as a reference for relevant medical decision-making.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.