Objective To investigate the heterogeneity and key molecular features of epithelial cells in triple-negative breast cancer (TNBC), identify prognostic biomarkers, and develop a robust survival prediction model. Methods Using TNBC single-cell transcriptomic data, epithelial cells were extracted, normalized, and subclustered to characterize their molecular signatures and functional differences. High-dimensional weighted gene co-expression network analysis (hdWGCNA) was applied to establish co-expression modules in epithelial cells. Multiple machine learning algorithms were integrated to select key prognostic genes and develop a risk-score model, whose performance was evaluated using receiver operating characteristic (ROC) curves and Kaplan-Meier (K-M) survival analysis. In addition, the immune microenvironment features and potential drug-response differences between the high- and low-risk groups were systematically assessed. Finally, PCR was performed to validate the expression differences of the key genes between tumor and normal tissues. Results We characterized the composition and molecular features of TNBC epithelial subpopulations and identified a TNBC-associated epithelial subset. By integrating hdWGCNA with machine learning approaches, 10 key genes were selected to construct a prognostic model, which effectively stratified patients into distinct survival-risk groups and demonstrated favorable predictive performance in ROC and K-M analyses. Immune profiling revealed the differences in the infiltration levels of seven immune cell types and immune function-related features between the high- and low-risk groups. Drug-sensitivity analysis suggested potential differential responses to eight agents across the risk groups. PCR validation further confirmed the differential expression of the ten signature genes between tumor and normal tissues. Conclusion This study reveals epithelial heterogeneity in TNBC at single-cell resolution and establishes a 10-gene prognostic model, which may facilitate the stratification of TNBC risk and the evaluation of immune characteristics and potential therapeutic strategies.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Lung cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and its treatment continues to face major challenges such as therapeutic resistance and tumor recurrence. Pyroptosis, a newly characterized form of programmed cell death, induces tumor cell death through gasdermin-mediated membrane pore formation and is accompanied by the release of inflammatory mediators, thereby playing complex roles in lung cancer initiation, progression, and modulation of the tumor microenvironment. Active components and herbal formulas derived from traditional Chinese medicine can modulate pyroptosis-related signaling pathways through multi-target mechanisms, showing potential advantages in inducing lung cancer cell death, inhibiting proliferation and migration, and reversing chemoresistance. This review systematically summarizes relevant studies from domestic and international sources, focusing on the molecular mechanisms of pyroptosis, its roles in lung cancer development and tumor microenvironment remodeling, and the current research progress on traditional Chinese medicine-based interventions targeting pyroptosis, with the aim of providing references for the prevention and treatment of lung cancer using traditional Chinese medicine.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

This paper summarizes professor LIN Yi's clinical experience in treating brain metastases of triple-negative breast cancer （TNBC）. It is believed that the pathogenesis of this disease is fundamentally based on spleen and lung qi deficiency， with the binding of phlegm， stasis， and toxins acting as the critical link for disease progression， and qi stagnation serving as a major factor in its protracted course. The core therapeutic principle of "consolidating the root and cultivating the origin， resolving phlegm and dredging collaterals" is proposed. Clinically， the disease is staged into active， stable， and convalescent phases. During the active phase， characterized by spleen and lung qi deficiency alongside hyperactivity of phlegm-toxin pathogens， the treatment focuses on supplementing qi， fortifying the spleen， resolving phlegm， and dredging collaterals， utilizing the Yiqi Jiangtan Tongluo Formula （益气降痰通络方）. During the stable phase， marked by spleen deficiency， weak qi， and residual phlegm， stasis， and toxins lingering in the collaterals， the treatment aims to fortify spleen， cultivate the origin， expel pathogens， and dredge collaterals， using modified Baihua Qiling Formula （白花芪苓方）. During the convalescent phase， characterized by depletion of healthy qi， dysfunction of zang-fu （脏腑） organs， and deep-seated residual phlegm， stasis， and toxins within the brain collaterals， the treatment focuses on regulating qi movement， protecting body fluids， and applying constitution-based treatments， mostly using mild and nourishing medicinals.

This paper summarizes professor LIN Yi's clinical experience in treating brain metastases of triple-negative breast cancer （TNBC）. It is believed that the pathogenesis of this disease is fundamentally based on spleen and lung qi deficiency， with the binding of phlegm， stasis， and toxins acting as the critical link for disease progression， and qi stagnation serving as a major factor in its protracted course. The core therapeutic principle of "consolidating the root and cultivating the origin， resolving phlegm and dredging collaterals" is proposed. Clinically， the disease is staged into active， stable， and convalescent phases. During the active phase， characterized by spleen and lung qi deficiency alongside hyperactivity of phlegm-toxin pathogens， the treatment focuses on supplementing qi， fortifying the spleen， resolving phlegm， and dredging collaterals， utilizing the Yiqi Jiangtan Tongluo Formula （益气降痰通络方）. During the stable phase， marked by spleen deficiency， weak qi， and residual phlegm， stasis， and toxins lingering in the collaterals， the treatment aims to fortify spleen， cultivate the origin， expel pathogens， and dredge collaterals， using modified Baihua Qiling Formula （白花芪苓方）. During the convalescent phase， characterized by depletion of healthy qi， dysfunction of zang-fu （脏腑） organs， and deep-seated residual phlegm， stasis， and toxins within the brain collaterals， the treatment focuses on regulating qi movement， protecting body fluids， and applying constitution-based treatments， mostly using mild and nourishing medicinals.

ObjectiveTreadmill exercise intervention was evaluated for its effects on addictive behavior, learning and memory, and hippocampal neuroinflammation in methamphetamine (MA)-addicted mice, and transcriptomic screening was performed to identify candidate molecules involved in exercise-mediated attenuation of MA-related neuronal injury. MethodsTwo-month-old male C57BL/6 mice were randomly assigned to four groups: control (C), exercise control (CE), methamphetamine (M), and methamphetamine plus exercise (ME). Mice in the M and ME groups received intraperitoneal injections of MA (1 mg/kg) once daily for 7 consecutive days to establish the addiction model, whereas mice in the C and CE groups received equal volumes of saline. Subsequently, mice in the CE and ME groups underwent treadmill exercise at 12 m/min for 60 min/d for 2 weeks. Conditioned place preference (CPP), the Y-maze, and the Morris water maze (MWM) were used to assess addictive behavior, spatial recognition memory, and spatial learning and memory, respectively. Hippocampal neuronal ultrastructure was examined by transmission electron microscopy (TEM), and microglia-related responses were evaluated by immunofluorescence staining for ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampal CA1 region. Previously generated and publicly available RNA-seq data from brain tissue of the C, M, and ME groups were reanalyzed, with three biological samples per group. Differentially expressed genes (DEGs) were re-screened using the criteria of P<0.05 and fold change>1.5 or <0.67, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. NLR family CARD domain containing 5 (Nlrc5) was further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot was used to determine the protein expression of NLRC5, nuclear factor kappa B (NF‑κB), interleukin-1β (IL-1β), postsynaptic density-95 (PSD-95), and synaptophysin. ResultsTreadmill exercise significantly attenuated MA-induced conditioned place preference and improved learning and memory performance in both the Y-maze and MWM tests. Exercise increased exploration time and distance in the novel arm of the Y-maze, shortened escape latency, and increased the number of platform crossings in the MWM. Average swimming speed during the probe trial did not differ significantly among groups, suggesting that the MWM differences were not attributable to obvious differences in swimming performance. TEM revealed that MA exposure induced mitochondrial swelling, disrupted cristae, reduced organelle abundance, and nuclear envelope abnormalities in hippocampal neurons, whereas these ultrastructural changes were alleviated after exercise. Immunofluorescence staining showed that MA increased Iba-1 fluorescence intensity in the hippocampal CA1 region, while treadmill exercise significantly reduced this change. Transcriptomic analysis identified 160 DEGs associated with MA exposure and 58 DEGs associated with exercise intervention, with 9 overlapping DEGs. KEGG enrichment analysis showed that MA-related DEGs were enriched in the NOD-like receptor signaling pathway. Among the overlapping DEGs, Nlrc5, which was downregulated after MA exposure and restored following exercise intervention, was selected as a candidate gene for further validation. RT-qPCR confirmed that treadmill exercise reversed the MA-induced decrease in Nlrc5 mRNA expression. Western blot analysis further showed that treadmill exercise increased NLRC5, PSD-95, and synaptophysin protein expression while reducing NF-κB and IL-1β expression. ConclusionTwo weeks of treadmill exercise attenuated MA-induced conditioned place preference and ameliorated learning and memory impairment, alleviated hippocampal neuroinflammation and neuronal ultrastructural damage, and restored the expression of synapse-related proteins. Transcriptomic screening combined with molecular validation demonstrated that exercise intervention was accompanied by restoration of NLRC5 expression, reduced NF‑κB and IL-1β expression, and increased PSD-95 and synaptophysin expression. These findings suggest that NLRC5 may represent a candidate molecule involved in exercise-mediated amelioration of MA-related neuronal injury. However, the present results mainly demonstrate coordinated changes in NLRC5 expression, inflammatory indicators, and cognitive outcomes rather than a direct causal relationship, and the specific role of NLRC5 requires further functional validation.

ObjectiveTo investigate the general situation， dietary factors， and clinical features of patients with recurrent primary common bile duct stones， and to provide a basis for effective prevention of stone recurrence. MethodsA retrospective analysis was performed for 23 730 patients who underwent cholecystectomy due to cholelithiasis in Department of Hepatobiliary， Pancreatic and Spleen Surgery， Inner Mongolia People’s Hospital， from January 2013 to December 2023， and according to the presence or absence of recurrence of primary common bile duct stones after surgery， 334 patients were divided into recurrence group. The recurrence group was further analyzed based on sex in terms of recurrence rate， recurrence cycle， recurrence age， recurrence type， and general， disease， imaging， and dietary factors. The independent-samples t test was used for comparison of continuous data between two groups， the chi-square test was used for comparison of categorical data between two groups. ResultsThere were 334 cases of recurrence of primary bile duct stones after cholecystectomy， with a recurrence rate of 1.41%， and the highest frequency of recurrence cycle was observed in 10 years after surgery， with a significant difference in recurrence cycle between the male and female patients （t=5.238， P<0.001）. There was a significant difference in the recurrence rate of stones after surgery between the patients with simple gallstones and those with gallbladder and common bile duct stones at initial diagnosis （1.23% vs 2.76%， χ²=42.104， P<0.001）. The patients with recurrence aged >60 years accounted for the highest proportion in the whole population and in both male and female populations， and 92% were Han residents； 10% of the patients with recurrence had a family history of gallstones， and as for comorbidities， the patients with hypertension accounted for the highest proportion. Among the patients with recurrence， the patients with smoking or drinking accounted for 76.7% and 10.3%， respectively. As for body weight， 63.8% of the patients with recurrence had a normal body mass index （BMI）， and 23.2% of the patients were overweight； compared with body weight at the time of the first gallbladder surgery， a reduction in body weight was observed in 60.1% of the patients with recurrence， while an increase in body weight was observed in 22.9% of the patients with recurrence. There were significant differences between the male and female patients with recurrence in age composition， ethnicity， the type of place of residence， comorbidities， smoking， drinking， BMI， and the change in body weight （all P<0.001）. As for the type of stone recurrence， the ratio of multiple stones， solitary stones， and muddy stones was 74∶15∶11， and the stone size of <1 cm， 1-2 cm， and >2 cm accounted for about 40.5%， 48.8%， and 10.6%， respectively. As for the surgical procedure， the patients undergoing laparotomy accounted for 66.1%， and those undergoing laparoscopy accounted for 33.9%. The patients with various types of dyslipidemia accounted for a percentage of<30%. There were significant differences between the male and female patients with recurrence in the type of stones at initial onset， the type and size of stones， and surgical procedure （all P<0.001）. Imaging data showed that 4 patients had an abnormal structure of the bile duct， manifesting as long and curve cystic ducts， and 73.1% of the patients had common bile duct dilatation after surgery. The follow-up of dietary factors showed irregular diets in 55.8% of the patients with recurrence. As for the dietary structure， meat and staple food accounted for 43.8% and 37.8%， respectively， which showed a sex difference， with meat in male patients and staple food in female patients； 64.1% of the patients with recurrence had a high-salt and high-oil diet； 59.8% of the patients had changes in diet after the first surgery for stones， among whom 80% were able to have a regular diet， and the patients with a regular diet accounted for 92%. ConclusionThere is a relatively low recurrence rate of primary common bile duct stones in this area， and there is no sex difference. The peak of recurrence is 10 years after surgery， and recurrence of stones is mainly observed in the population aged >60 years. The analysis of dietary and clinical features can help doctors and patients to further understand the characteristics of the recurrence of primary common bile duct stones and provide a basis for subsequent targeted prevention.

Objective To investigate the mechanism by which angiotensin Ⅱ type 1 receptor autoantibody(AT1-AA)promotes phenotypic switch of vascular smooth muscle cells(VSMCs)and vascular fibrosis through abnormal expression of circadian clock protein BMAL1.Methods Twelve male SD rats(6～8 weeks old,weighing 180～220 g)were randomly divided into(n=6)a control group and an AT1-AA-positive group[established by active immunization of SD rats with AT1R extracellular loop Ⅱ peptide(AT1R-ECLⅡ)].HE and Masson stainings were used to observe structural changes and fibrosis in the thoracic aorta(n=3).Western blotting was performed to detect the expression of Collagen I,phenotypic switch-related proteins(SM22,α-SMA,OPN and MMP2)in vascular tissues and primary VSMCs(n=4),as well as the expression of BMAL1 at CT0,CT4,CT8,CT12,CT16,and CT20.Transwell and scratch assays were used to assess the proliferation and migration of VSMCs(n=3).si-RNA was employed to knock down Bmal1,followed by detection of BMAL1,Collagen I,and phenotypic conversion-related protein expression(n=3).Additionally,AT1-AA-positive AT1R-knockout(AT1R-KO)rats were constructed to measure BMAL1 expression in thoracic aortic tissues(n=4).Results The AT1-AA-positive rats had significantly thickened thoracic aortic vessel wall[(140±9)%vs(120±5)%,P<0.05],badly arranged VSMCs,obvious blue Masson staining,and up-regulated Collagen I expression(P<0.05).In the thoracic aorta of AT1-AA-positive rats and AT1-AA-treated VSMCs,the expression of contractile phenotype-related proteins(α-SMA,SM22)was decreased(P<0.05),while the expression of synthetic phenotype-related proteins(OPN,MMP2)was increased(P<0.05).AT1-AA enhanced the scratch healing ability and migration ability of VSMCs.Furthermore,both mRNA and protein levels of Bmal1 were significantly up-regulated at CT12(P<0.05),and the rhythmicity of Bmal1 was lost.Knockdown of Bmal1 partially ameliorated AT1-AA-induced phenotypic switch of VSMCs.Compared with AT1-AA-positive WT rats,AT1-AA-positive AT1R-KO rats showed significantly reduced BMAL1 expression in the thoracic aorta(1.35±0.06 vs 0.86±0.07,P<0.001).At the cellular level,AT1-AA-induced phenotypic switch and high Collagen I expression in VSMCs were partially improved in AT1R-KO VSMCs.Conclusion AT1-AA promotes VSMCs phenotypic conversion and vascular fibrosis through the AT1R-Bmal1 axis.