Traditional Chinese medicine （TCM）， through its multi-target and systematic regulatory effects， has demonstrated unique advantages in the treatment of gastric precancerous lesions （GPL）. At present， TCM theoretical research on GPL is mainly reflected in three aspects， the integration of macroscopic syndrome differentiation， the inflammation-carcinoma transformation mechanism， as well as the systematization and scientization of theoretical inheritance from famous TCM practitioners. High-quality evidence-based research findings serve as the foundation for clinical practice guidelines on GPL， and TCM has gained international academic recognition in the field of GPL prevention and treatment. Research on TCM mechanisms has yielded a series of important outcomes in the aspects of signaling pathways， gene expression regulation， cellular epigenetics， histone modification， and intestinal microecology. It is proposed that future research on GPL should focus on four key directions， establishing multi-omics data， exploring targeted intervention strategies on key regulatory nodes， advancing the standardization process of integrated traditional Chinese and western medicine prevention and treatment technologies， and constructing stratified screening and intervention platforms. The in-depth integration of TCM microcosmic mechanism of action with its macroscopic syndrome differentiation and treatment system， coupled with interdisciplinary research， will provide valuable references for the clinical treatment and scientific research of GPL.

Objective: To explore the relationship between snack consumption and depressive symptoms in first year junior high school students with different left behind experiences in Yunnan Province, so as to provide a basis for improving depressive symptoms among first year junior high school students with different left behind experiences. Methods: From October to December 2022,a cluster random sampling method was used to select 8 500 first year junior high school students from 11 ethnic minority areas (Fugong County, Longling County, Longyang District, Luchun County, Mojiang County, Nanjian County, Qiaojia County, Shuangjiang County, Tengchong City, Yuanmou County, Zhenyuan County) in Yunnan Province for a questionnaire survey. The Chinese version of Depression Anxiety Stress Scale-21 was applied to assess depressive symptoms in first year junior high school students, and snack consumption was collected by employing food frequency questionnaire. The generalized linear model was used to analyze the association between first year junior high school students snack consumption and depressive symptoms, and the analysis was stratified according to left behind experience. Results: The detection rates of depressive symptoms among firstyear junior high school students with and without left behind experience were 36.25% and 26.91%, respectively. After controlling for confounding variables, the generalized linear model analysis showed that sweet snacks ( β=0.16, 95%CI =0.07-0.25), fast food ( β=0.14, 95%CI =0.04-0.23) and carbonated drinks ( β=0.09, 95%CI =0.01-0.17) of first year junior high school students with left behind experience (all P <0.05). Compared with those without such behavior, the risk of depressive symptoms was higher in consumption of fast food ( β=0.13, 95%CI =0.07-0.18) and carbonated drinks ( β=0.10, 95%CI =0.06-0.15)among first year junior high school students without left behind experience (both P <0.05). Conclusion Snack consumption among first year junior high school students in Yunnan may increase the risk of developing depressive symptoms, while first year junior high school students with left behind experience may have a greater risk of developing depressive symptoms.

Malignant tumors represent a major threat to global health. Conventional anti-tumor pharmacotherapy often encounters challenges such as drug resistance, highlighting an urgent need for the development of novel therapeutic strategies. Fatty acid synthase (FASN), the key enzyme catalyzing de novo fatty acid synthesis, is subject to precise regulation at multiple levels, including transcriptional control, various post-translational modifications such as ubiquitination and phosphorylation, as well as modulation by diverse signaling pathways. Recent studies have revealed that FASN is aberrantly overexpressed in various malignant tumors and is closely associated with tumor progression and poor patient prognosis. FASN is a homodimer composed of seven functional domains that catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to generate saturated fatty acids, primarily palmitic acid. Its stability is regulated by multiple ubiquitin ligases and deubiquitinating enzymes. Additionally, FASN is subject to upstream regulation via neural precursor cell-expressed developmentally downregulated 8 (Nedd8) modification and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, thereby establishing a metabolic-signaling positive feedback loop. As a core executor of metabolic reprogramming, FASN promotes tumorigenesis through dual mechanisms. First, its fatty acid synthesis product, palmitate, participates in membrane phospholipid synthesis, lipid raft formation, and protein palmitoylation, thereby activating several key oncogenic signaling pathways, including PI3K/AKT/mTOR, wingless-type MMTV integration site family member (Wnt)/β‑catenin, and signal transducer and activator of transcription 3 (STAT3)/matrix metalloproteinase (MMP), leading to tumor development and progression. Second, FASN plays a pivotal role in modulating the anti-tumor functions of immune cells and remodeling the tumor immune microenvironment. Specifically, FASN enhances immune checkpoint inhibition by inducing programmed death-ligand 1 (PD-L1) palmitoylation, suppresses the activation of cytotoxic T lymphocytes and natural killer cells, and promotes the polarization of M2-type macrophages, consequently facilitating tumor immune evasion and malignant progression. Precisely due to its significant overexpression in tumor cells, its critical functional role, and its differential expression compared to normal cells, FASN has emerged as a highly promising target for anti-tumor drug development. Highly selective small-molecule inhibitors, notably represented by TVB-2640, have advanced to clinical trial stages and demonstrated favorable anti-tumor activity. Furthermore, the combination of FASN inhibitors with other chemotherapeutic agents or targeted drugs can overcome the limitations of monotherapy through synergistic effects or by resensitizing tumor cells to conventional drugs, achieving a “1+1>2” therapeutic outcome. With the advancement of modern traditional Chinese medicine (TCM), numerous active ingredients derived from TCM have been confirmed to exert anti-tumor effects by modulating FASN-related pathways. This integrated approach leverages the precision of Western medicine while simultaneously harnessing the holistic regulatory benefits of TCM to alleviate the side effects of radiotherapy and chemotherapy. Despite the promising prospects of FASN-targeted therapies, challenges remain, including tumor cell metabolic plasticity, tumor context-dependent responses, and heterogeneity. This review systematically summarizes the molecular structure, physiological functions, and mechanisms of FASN in tumorigenesis, as well as recent advances in targeted therapies. Future directions—including the precise identification of responsive patient populations using spatial transcriptomics, the development of novel combination regimens, and the active exploration of integrative strategies combining traditional Chinese and Western medicine—will facilitate the clinical translation of FASN-targeted therapies and open new avenues for improving the quality of life and prognosis of cancer patients.

The aim of this study was to investigate the improvement effect of Wenpi Pills(WPP) on non-alcoholic fatty liver disease(NAFLD). The experiment was divided into two parts, using C57BL/6 mouse models induced by a high-fat diet(HFD) and a methionine and choline deficiency diet(MCD). The HFD-induced experiment lasted for 16 weeks, while the MCD-induced experiment lasted for 6 weeks. Mice in both parts were divided into four groups: control group, model group, low-dose WPP group(3.875 g·kg~(-1), WPP＿L), and high-dose WPP group(15.5 g·kg~(-1), WPP＿H). After sample collection from the HFD-induced mice, lipid content in the serum and liver, liver function indexes in the serum, and hepatic pathology were examined. Real-time fluorescent quantitative reverse transcription PCR(qRT-PCR) was used to detect the expression of lipid-related genes. After sample collection from the MCD-induced mice, serum liver function indexes and inflammatory factors were measured, and hepatic pathology and lipid changes were analyzed by hematoxylin-eosin(HE) staining and widely targeted lipidomic profiling, respectively. The results from the HFD-induced experiment showed that, compared with the HFD group, WPP administration significantly reduced the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in the serum, with the WPP＿H group showing the most significant improvement. HE staining results indicated that, compared with the HFD group, WPP treatment improved the morphology of white adipocytes, reducing their size, and alleviated hepatic steatosis and lipid droplet accumulation. The qRT-PCR results suggested that WPP might increase the mRNA expression of liver cholesterol-converting genes, such as liver X receptor α(LXRα) and cytochrome P450 family 27 subfamily A member 1(CYP27A1), as well as lipid consumption genes like peroxisome proliferator-activated receptor α(PPARα) and adenosine mono-phosphate-activated protein kinase(AMPK). Meanwhile, WPP decreased the mRNA expression of lipid synthesis genes, including fatty acid synthetase(FAS), stearoyl-CoA desaturase 1(SCD1), and sterol regulatory element-binding protein 1c(SREBP-1c), thereby reducing liver lipid accumulation. The results from the MCD-induced experiment showed that, compared with the MCD group, WPP administration reduced the levels of ALT, AST, and inflammatory factors in the serum, thereby alleviating liver injury and the inflammatory response. HE staining of liver tissue indicated that WPP effectively improved hepatic steatosis. Non-targeted lipidomics analysis showed that WPP improved lipid metabolism disorders in the liver, mainly by affecting the metabolism of TG and cholesterol esters. In conclusion, WPP can improve hepatic lipid accumulation in NAFLD mice induced by both HFD and MCD. This beneficial effect is primarily achieved by alleviating liver injury and inflammation, as well as regulating lipid metabolism.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Lipid Metabolism/drug effects* ; Mice ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Diet, High-Fat/adverse effects* ; Liver/drug effects* ; Humans ; Disease Models, Animal ; Methionine

Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*

Osteoarthritis (OA) is the most common degenerative joint disease. Its pathological process is related to inflammatory response, chondrocyte apoptosis, and cartilage degeneration. Hippo-yes-associate protein(YAP) signaling pathway plays an important role in mediating organ size and tissue homeostasis. In recent years, the key effector protein YAP in the Hippo-YAP pathway has become a research hotspot in osteoarthritis. This article introduces the activation process of Hippo-YAP signaling pathway and the biological role of YAP. It reviews the progress of YAP in regulating osteoarthritis by influencing the proliferation and differentiation of mesenchymal stem cells and the proliferation, differentiation, and apoptosis of articular chondrocytes. It analyzed the problems encountered in YAP research in OA, introduces the research potential of YAP in other orthopedic diseases, and provides new ideas for subsequent research in Osteoarthritis.
Osteoarthritis/metabolism* ; Humans ; Signal Transduction ; Protein Serine-Threonine Kinases/physiology* ; Hippo Signaling Pathway ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/physiology* ; Animals ; Transcription Factors ; Chondrocytes/cytology* ; Cell Cycle Proteins

OBJECTIVE: To investigate the molecular mechanism of weak D phenotype in a Chinese family. METHODS: Routine Rh typing tests were performed first, and RHD exons 1-10 of the proband and his family members were sequenced by first-generation sequencing. RHD zygosity was also determined. Third-generation sequencing was used to analyze the haplotypes of the RHD gene. RESULTS: The proband showed a weak D serological phenotype. First-generation sequencing revealed a c.787G>A point mutation in exon 5. The family pedigree investigation showed that the proband and his younger sister had the same serological phenotype and molecular mechanism. His father carried this gene mutation, while his mother and younger brother were normal. Hybrid box was not detected, suggesting that all the family members did not have a haplotype with a complete deletion of the RHD gene. The results of third-generation sequencing showed that the proband and his sister inherited the weak D allele from their father and the non-functional allele RHD -CE(3-9)-D from their mother, respectively. CONCLUSION Third-generation sequencing technology enables haplotype analysis of the RHD gene and can detect complex genotypes such as genetic exchanges between RHD and RHCE combined with other mutations.
Female ; Humans ; Male ; Alleles ; Exons ; Genotype ; Haplotypes ; High-Throughput Nucleotide Sequencing ; Pedigree ; Phenotype ; Rh-Hr Blood-Group System/genetics* ; East Asian People/genetics*

An assay was established for detection of toxigenic Clostridioides difficile by combining microfluidic chip analysis with immunochromatography,and its performance was evaluated and compared with those of the Xpert C.difficile/Epi and VIDAS CD AB tests.Primer pairs were designed according to the tcdB and tpi genes in C.difficile.The specificity,limit of detection,reproducibility,and stability were evaluated.A total of 215 stool samples from patients with diarrhea were collected and tested in parallel with the Xpert C.difficile/Epi,VIDAS CDAB,and our assay.C.difficile was isolated from samples,and the tcdB gene was identified when discrepant results were obtained from the three above assays.Our assay showed no cross-reaction with other diarrhea-associated pathogens.Its reproducibility was 100％in testing of two standard plasmids containing tcdB and tpi genes at two concentrations(105 and 102 copies/μL).Two standard plasmids were detected after the PCR and immunochromatography reagents had been stored for 3,6,9,and 12 months,and all the results were posi-tive.The limit of detection was 10 copies/μL for toxigenic C.difficile.Testing of 33 samples positive for C.difficile with our assay(33/215,15.3％)yielded findings statistically coherent with those of the Xpert C.difficile/Epi test(kappa value=0.965).The sensitivity,specificity,positive predictive value,and negative predictive value of our assay,with respect to Xpert C.difficile/Epi as the standard,were 94.3％,100.0％,100.0％,and 98.9％;these values were significantly higher than those of VIDAS CDAB(60.0％,98.9％,91.3％,and 92.7％)(Kappa=0.714,OR=157.50,95％CI:62.03-847.28,P=0.013).In conclusion,our newly developed assay is specific,stable,and reproducible,and may be used for rapid and accu-rate detection of toxigenic C.difficile.The assay could be used for C.difficile infection screening in outpatient and emergen-cy,community medical service center,and epidemiological settings.

A 35-year-old female patient with advanced lung cancer was treated with paclitaxel(albumin-bound)and carboplatin chemotherapy,combined with tislelizumab immunotherapy for one cycle.After 6 days of treatment,the patient developed sagging of the right eyelid compared to the leftside,mild morning and heavy evening,systemic muscle soreness,abnormal transaminases and myocardial enzymes,and abnormal electrocardiogram.It is suspected that there may be a correlation between tislelizumab and myasthenia gravis or related myositis.After admission,patients were treated with methylprednisolone,intravenous immunoglobulin,plasma exchange,mycophenolate mofetil,temporary pacemaker installation,and tracheal intubation.After more than a month of treatment,the patient's indicators decreased,but the patient became unconscious,the patient's family requested discharge.The association between the multisystem adverse reactions and tislelizumab was evaluated using the Naranjo's Assessment Scale,the correlation score was 7 and evaluated as probably relevant.It is suggested that when using tislelizumab in clinical practice,risk factor assessment and medication monitoring should be strengthened to ensure drug safety.

Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.