1.Ameliorating Effect of Yifei Tongluo Prescription on Bleomycin-induced Pulmonary Fibrosis in Rats via Regulating NLRP3/Caspase-1/GSDMD Signaling Pathway and Epithelial-mesenchymal Transition
Bowen ZHOU ; Zefeng LI ; Xian MA ; Xuannian LI ; Jingwen WANG ; Fei XU ; Huaman LIU ; Xinhua JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):150-159
ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pathway and epithelial-mesenchymal transition (EMT) in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group, a prednisone acetate group (1.17 mg·kg-1), and low- and high-dose Yifei Tongluo prescription groups (10.62 and 21.24 g·kg-1, respectively). Administration started on the 7th day after modeling, once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression of α-smooth muscle actin (α-SMA) and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome, E-cadherin (E-cad), and typeⅠ collagen (ColⅠ) in lung tissues was detected by immunofluorescence. The content of hydroxyproline (HYP), tumor necrosis factor (TNF)-α, interleukin (IL)-18, and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), IL-1β, and transforming growth factor (TGF)-β1 in rat lung tissues were determined by real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of NLRP3, GSDMD, ASC, and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group, the model group exhibited a significantly increased lung coefficient (P<0.01) and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition, the levels of α-SMA, Vimentin, E-cad, and ColⅠ in lung tissues were significantly increased (P<0.01). The levels of fibrosis- and inflammation-related factors HYP, TNF-α, IL-18, and IL-1β in serum were significantly upregulated (P<0.01). The levels of factors related to the activation of NLRP3 inflammasome in lung tissues, including NLRP3, GSDMD, ASC, Caspase-1, IL-1β, and TGF-β1, were significantly upregulated (P<0.01). Compared with the model group, the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally, the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA, Vimentin, E-cad, and ColⅠ in lung tissue was significantly decreased (P<0.01). The levels of HYP, TNF-α, IL-18, and IL-1β in serum were significantly reduced (P<0.01). The expression levels of NLRP3, GSDMD, ASC, Caspase-1, IL-1β, and TGF-β1 in lung tissue were also significantly decreased (P<0.01). ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway, down-regulate release of pro-inflammatory and pro-fibrotic cytokines, alleviate NLRP3 inflammasome-mediated pyroptosis and EMT, and thereby improve pulmonary fibrosis in rats.
2.Effect and Mechanism of Modified Sini San on Improving Intestinal Mucosal Barrier of Chronic Stress Rats via Regulating Short-chain Fatty Acid Metabolism and Inhibiting HMGB1/RAGE Signaling Pathway
Youlan KE ; Yingying YUE ; Zicheng WANG ; Yaoxue SHANG ; Xian ZHOU ; Yu CHEN ; Songlin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):31-41
ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids (SCFAs) and high mobility group protein B1 (HMGB1)/receptor of advanced glycation end products (RAGE) signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group,model group,low-dose modified Sini San group (7.34 g·kg-1·d-1),high-dose modified Sini San group (14.68 g·kg-1·d-1),and Fructo-oligosaccharides group (3.15 g·kg-1·d-1),with 10 rats in each group. Except for the control group,all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling,each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors,body weight,Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin (HE) staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry (GC-MS). Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1,Occludin,and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay (ELISA). ResultsCompared with the model group,the sucrose preference rate,total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased (P<0.05, P<0.01),and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced (P<0.05, P<0.01). Meanwhile,the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased (P<0.05). The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased,with a obviously increase in the content of acetic acid,propionic acid,butyric acid,and isovaleric acid (P<0.05, P<0.01) and the expression levels of HMGB1,RAGE,Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),tumor necrosis factor-α(TNF-α),and nuclear factor kappa-B p65(NF-κB p65) proteins in cecal tissue were significantly decreased (P<0.05, P<0.01) in low-dose group of modified Sini San. Meanwhile,the contents of ZO-1,Occludin,and Claudin-1 in the cecal tissue were obviously increased (P<0.01) in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.
3.Effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparo-scopic cholecystectomy
Zhangzhen ZHONG ; Xian ZHENG ; Ting XU ; Jie WANG ; Hui CAO ; Xinggen ZHOU ; Hui LI ; Jiacheng ZHAO ; Hui LIU ; Chao ZHANG
China Pharmacy 2026;37(2):204-209
OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group (n=100) and observation group (n=100). One minute before the initiation of anesthesia, patients in the control group received intravenous injections of Propofol emulsion injection, Sufentanil citrate injection, and Succinylcholine chloride injection. On this basis, patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared, along with their general intraoperative conditions (including sufentanil dosage, duration of pneumoperitoneum, operative time, anesthesia time, and extubation time), postoperative recovery, incidence of adverse reactions, and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure, entropy index (state entropy and response entropy), inflammatory marker levels [interleukin-6 (IL-6) and C-reactive protein (CRP)], numerical rating scale (NRS) for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration, operative time, anesthesia time,extubation time, incidence of postoperative dry mouth, entropy index or length of stay in the post-anesthesia care unit (P>0.05). Compared with the control group, the observation group showed significantly lower postoperative STAI-S scores, reduced intraoperative sufentanil consumption, decreased incidence of postoperative nausea, vomiting, and shivering, the need for dezocine rescue analgesia, as well as lower plasma IL-6 and CRP levels at 24 h after surgery, and NRS (P<0.05). The heart rate and mean arterial pressure of patients in the observation group at the start of surgery, end of surgery, and during extubation were all significantly higher than those in the control group (P<0.05). CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety, reduce intraoperative opioid consumption, suppress postoperative inflammatory response, relieve postoperative pain, and promote recovery in patients undergoing laparoscopic cholecystectomy.
4.The Neural Circuit Characteristics of Repetitive Transcranial Magnetic Stimulation Over The Dorsolateral Prefrontal Cortex for The Treatment of Migraine
Chen-Xia JIN ; Bo-Lin TAN ; Yang YE ; Ji-Qing HE ; Ling-Yan WANG ; Zhong-Ming GAO ; Yu-Jun WANG ; Hui-Li LIU ; Yong-Xing YAN ; Xian-Wei CHE
Progress in Biochemistry and Biophysics 2026;53(7):1953-1968
ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.
5.Individual monitoring results of occupational external exposure for radiation workers in Beijing pet hospital, 2022–2024
Hongfeng ZHAO ; Xian XUE ; Jiejun LI ; Yanhui GAO ; Yaning LIU ; Yiyun WANG ; Yibing TIAN ; Hui XU
Chinese Journal of Radiological Health 2026;35(3):336-342
Objective To analyze personal external exposure dose monitoring results of pet hospital radiation workers in Beijing from 2022 to 2024, and to provide scientific evidence for developing effective monitoring protocols, standardizing radiological practices in pet hospitals, and protecting the health of both workers and the public. Methods Personal dose equivalents, Hp(10), were measured using GR-200A thermoluminescent dosimeters. Monitoring included radiation workers at 286 pet hospitals across all 16 districts of Beijing from 2022 to 2024. Each monitoring cycle lasted no more than 90 days. Annual effective doses were calculated by summing the results of four consecutive quarterly cycles. Data were processed and analyzed using Access and TLPS 6.41 software. All evaluations complied with national laws, regulations, and technical standards. Results A total of 1,579 person-time measurements were recorded. Only 51.87% of workers completed the full four-cycle annual monitoring schedule. Over the study period, the mean annual effective dose was 0.29 mSv, and the median dose was 0.14 mSv. The collective effective dose was 238.34 man-mSv. Notably, 94.26% of workers had annual effective doses below 1.0 mSv, and only 0.12% had doses at or above 5 mSv. Dose levels showed a statistically significant downward trend (P<0.05). Both independent and chain-branded clinics had a median annual effective dose of 0.14 mSv. In independent clinics, the proportion of workers with doses below 1.0 mSv increased from 80.77% in 2022 to 98.82% in 2024. In chain-branded clinics, this proportion rose from 96.88% to 98.11% over the same period. Conclusion Radiation exposure among pet hospital workers in Beijing remains at low levels, well below regulatory limits, and shows an overall declining trend. The disparity in personal doses between independent and chain-branded pet hospitals has diminished over time. Nevertheless, the industry still faces challenges such as high staff turnover and low monitoring completion rates. Expanding monitoring coverage and harmonizing protection standards would provide a scientific basis for precise, nationwide regulation.
6.The role and application of intestinal microecology in immune regulation of tuberculosis
Gaofeng PAN ; Hongdan LIU ; Xian ZHENG ; Hua YANG ; Maoying FU
Journal of Clinical Medicine in Practice 2025;29(17):120-125
Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis,pri-marily transmitted through respiratory droplets,and poses a significant global public health challenge.Despite the availability of vaccines and chemotherapy regimens,the emergence of drug resistance and high incidence rates continue to render the prevention and control situation severe.The intestinal mi-crobiota modulates host immunity through metabolites such as short-chain fatty acids,influencing macrophage function,T-cell differentiation,and inflammatory responses,thereby regulating tubercu-losis susceptibility,disease progression,and treatment responses.This review systematically summa-rized the role of intestinal microecology in immune regulation of tuberculosis and its potential applica-tion strategies,delved into the possible immune regulatory mechanisms,proposed that the interaction between intestinal microbiota and immune checkpoint inhibitors may serve as a warning for the clinical risk of tuberculosis reactivation,and analyzed the potential of intestinal microecology as a therapeutic target for tuberculosis.
7.Clinical characteristics analysis of secondary systemic capillary leak syndrome induced by acute organophosphorus pesticide poisoning
Yihong YANG ; Tengfei MA ; Qiqi LIU ; Hongbo LIU ; Xian WANG ; Yecheng LIU
Chinese Journal of Emergency Medicine 2025;34(4):582-587
Objective:To investigate the clinical characteristics and risk factors associated with secondary systemic capillary leak syndrome (SSCLS) induced by acute organophosphorus pesticide poisoning (AOPP). The goal is to enhance clinical understanding of this complication and provide a theoretical foundation for the early identification of high-risk patients and the optimization of individualized treatment strategies.Methods:Clinical data were collected from patients admitted to the Emergency Department of Fuyang People’s Hospital Affiliated to Anhui Medical University between October 2019 and October 2024, who were diagnosed with acute dichlorvos poisoning. The clinical features of SSCLS were described, and patients were categorized into SSCLS and non-SSCLS groups. Binary multivariate logistic regression analysis was conducted on statistically significant indicators to identify independent risk factors for SSCLS. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of these factors.Results:Among the 96 patients studied, 37 (38.5%) developed SSCLS. The median time from toxin ingestion to the onset of SSCLS was 3.0 (2.0-5.0) hours. In the 14 SSCLS survivors, the median duration of SSCLS was 50.0 (24-72) hours, whereas in the 23 non-survivors, it was 24.0 (12.0-35.0) hours. The mortality rate in the SSCLS group (62.16%, 23/37) was significantly higher than that in the non-SSCLS group (1.69%, 1/59) ( χ2=44.343, P<0.001). Blood toxin analysis detected trichlorfon components in 92 patients (95.83%). Binary multivariate logistic regression identified APACHE Ⅱ score and trichlorfon concentration (≥706.35 ng/mL) as independent risk factors for SSCLS ( P<0.05). ROC analysis revealed that the combination of these two factors had a higher predictive value ( P<0.05). Conclusions:In the diagnosis and treatment of acute dichlorvos (organophosphorus pesticide) poisoning, particular attention should be given to the combined toxic effects of dichlorvos and trichlorfon, which can lead to SSCLS. The onset and progression of SSCLS are rapid, and the condition is associated with a high mortality rate. Both APACHE Ⅱ scores and trichlorfon concentrations (≥706.35 ng/mL) are independent risk factors for the development of SSCLS, and their combined use enhances predictive accuracy. Early identification of high-risk patients and timely administration of individualized treatment are critical for reducing mortality rates. This revised abstract maintains the original meaning while improving clarity, flow, and readability. It ensures that the key points are presented in a structured and professional manner, suitable for a clinical audience.
8.Proteomics-based Investigation of Therapeutic Effect and Mechanism of Verbenalin on Lung Injury in Mice Infected with Human Coronavirus-229E
Qiyue SUN ; Shanshan GUO ; Shuangrong GAO ; Lei BAO ; Zihan GENG ; Shuran LI ; Ronghua ZHAO ; Jingsheng ZHANG ; Xian LIU ; Rui XIE ; Xiaolan CUI ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):69-78
ObjectiveTo evaluate the pharmacological effects of verbenalin on both in vitro and in vivo infection models of human coronavirus 229E (HCoV-229E) and to preliminarily explore the antiviral mechanism of verbenalin through proteomic analysis. MethodsIn vitro, the cell counting kit-8 (CCK-8) for cell proliferation and viability assessment was used to establish a model of HCoV-229E-induced injury in human lung adenocarcinoma cells(A549). A549 cells were divided into five groups: normal group, model group, and three verbenalin treatment groups (125, 62.5, and 31.25 μmol·L-1). The cell protective activity of verbenalin was evaluated through cell viability assay and immunofluorescence staining. In vivo, 30 BALB/c mice were randomly divided into normal group, model group, chloroquine group, and high-dose, low-dose verbenalin groups (40 and 20 mg·kg-1), with six mice per group. An HCoV-229E-induced mouse lung injury model was established to evaluate the therapeutic effects of verbenalin. Lung injury was assessed by detecting the lung index and lung inhibition rate. The severity of pulmonary inflammation cytokines was measured by enzyme-linked immunosorbent assay (ELISA), while the lung morphology and structure were analyzed by micro-computed tomography (Micro-CT). Hematoxylin and eosin (HE) staining was used to assess histopathological changes in lung tissue. Additionally, four-dimensional data-independent acquisition (4D-DIA) proteomics was employed to preliminarily explore the potential mechanisms of verbenalin in treating HCoV-229E-induced lung injury in mice, through differential protein expression screening, functional annotation, enrichment analysis, and protein-protein interaction network analysis. ResultsThe A549 cells were infected with HCoV-229E at the original viral titer for 36 hours to establish an in vitro infection model. The maximum non-toxic concentration of verbenalin was 125 μmol·L-1, and the half-maximal cytotoxic concentration (CC50) was 288.8 μmol·L-1. Compared with the normal group, the model group showed a significant decrease in cell viability (P<0.01), a significant increase in the proportion of dead cells (P<0.01), mitochondrial damage, and a significant reduction in mitochondrial membrane potential (P<0.01). After treatment with different concentrations of verbenalin (125, 62.5, and 31.25 μmol·L-1), cell viability was significantly increased (P<0.01), and the proportion of dead cells was reduced (P<0.01), with mitochondrial membrane potential restored (P<0.01). In vivo experiments further confirmed the therapeutic effect of verbenalin on HCoV-229E-infected mice. Compared to the normal group, the model group showed a significant increase in the lung index (P<0.01), severe lung tissue injury, lung volume enlargement, and a significant increase in the expression of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (P<0.01). In contrast, in the verbenalin treatment groups, these pathological changes were significantly improved, with a reduction in the lung index (P<0.01), alleviation of lung tissue injury, reduced lung volume enlargement, and a significant decrease in inflammatory cytokine expression (P<0.01). Proteomics analysis revealed that, compared to the normal group, the model group showed enrichment in several antiviral immune-related signaling pathways, including the nuclear factor-κB (NF-κB) signaling pathway (P<0.05). Compared to the model group, the verbenalin treatment group showed enrichment in several signaling pathways related to inflammatory response and autophagy (P<0.05), suggesting that verbenalin may exert its antiviral and anti-inflammatory effects by regulating these pathways. ConclusionVerbenalin demonstrates significant therapeutic effects in both in vitro and in vivo HCoV-229E infection models, with its mechanism likely related to the NOD-like receptor protein 3 (NLRP3) inflammasome pathway and mitochondrial autophagy.
9.Construction of milk donation of self-efficacy scale and test of reliability and validity for lost newborns based on COSMIN
Ronghua XIAN ; Ju YANG ; Li LIU ; Mei HE ; Yuan ZHANG ; Biao SHANG
Chinese Journal of Practical Nursing 2025;41(20):1581-1587
Objective:To develop a self-efficacy scale of milk donation and test its reliability and validity, in order to provide a scientific evaluation tool for the corresponding study.Methods:According to Bandura′s self-efficacy theory and consensus-based standards for the selection of health measurement instruments, the scale was developed by means of literature search, article pool establishment and expert letter consultation. A pre-survey was conducted on 30 newborn bereaved women, a formal investigation was conducted on 231 newborn bereaved women, and 115 newborn bereaved women were selected for exploratory factor analysis. Confirmatory factor analysis was performed on 116 parturients with neonatal loss to determine the reliability and validity of the scale.Results:The final scale includes 3 dimensions and 13 items. Three common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 77.962%. A scale with three dimensions, included breast milk donation resilience, breast milk donation cognition and breast milk donation motivation, and 13 items was determined. Confirmatory factor analysis showed that the model fit of the scale was good ( χ2/ df = 1.390, RMSEA = 0.063, RMR = 0.046, NFI = 0.924, NNFI = 0.971, GFI = 0.924, CFI = 0.977). The content validity index was 0.835. Cronbach′s α coefficient of the total volume table was 0.919, and the coefficients of each dimension were 0.892, 0.905 and 0.844, respectively. The broken half reliability of the scale was 0.893, and the broken half reliability of each dimension was 0.857, 0.881 and 0.711, respectively. The retest reliability of the scale was 0.814, and the retest reliability of each dimension was 0.803, 0.825 and 0.767, respectively. Conclusions:The scale has good reliability and validity, and can be used to evaluate the self-efficacy of milk donation in lost newborns.
10.Impact of KRAS,NRAS,and BRAF gene mutations on the efficacy of neoadjuvant therapy and postoperative hepatic metastasis occurrence in patients with stage Ⅱ-Ⅲ mid-low rectal cancer
Li-dan LUO ; Ping-ping LIU ; Xian-yin CHEN ; Da-chao CHEN
Chinese Journal of Current Advances in General Surgery 2025;28(6):451-456
Objective:To investigate the effect of KRAS,NRAS and BRAF gene mutations on the efficacy of pre-operative short-course radiotherapy combined with chemotherapy and postoperative liver metastasis in patients with stage Ⅱ~Ⅲ mid-low rectal cancer.Methods:The clinical data of 149 patients with stage Ⅱ~Ⅲ low rectal cancer admitted to Dongnan Hospital of Xiamen University from January 2017 to June 2020 were retrospectively analyzed.All patients received neoadjuvant therapy with preoperative short-course radiotherapy combined with chemotherapy and radical surgery,and were followed up until June 30,2023.The mutations of KRAS,NRAS and BRAF genes were de-tected by pathological tissue before surgery.The effect of neoadjuvant therapy was evaluated according to tumor re-gression grade(TRG).The risk factors of postoperative liver metastasis were analyzed by Logistic multivariate analysis.Results:There were 44 cases of KRAS,10 cases of NRAS and 12 cases of BRAF gene mutation in 149 patients with stage Ⅱ~Ⅲ low rectal cancer,and the mutation rates were 29.53%,6.71%and 8.05%.The incidence of positive vas-cular invasion in patients with KRAS gene mutation was higher than negative(P<0.05).In NRAS mutation patients,the incidence of positive lymph node metastasis was higher than negative(P<0.05),and the incidence of maximum tumor diameter≥5 cm was higher than that of maximum tumor diameter<5 cm(P<0.05).The clinical stage of BRAF muta-tion was higher in stage Ⅲ than in stage Ⅱ(P<0.05),and the incidence of positive lymph node metastasis was higher than negative(P<0.05).During the follow-up period,liver metastasis occurred in 42 patients,and the liver metastasis rate was 28.18%.The KRAS,NRAS and BRAF gene mutations in the effective group were 25.81%,2.15%and 3.23%,lower than those in the ineffective group(35.71%,14.29%and 17.07%,P<0.05).Multiple factors found clinical stage Ⅲ(OR=10.620,95%CI:2.645~22.575),lymph node metastasis was positive(OR=8.774,95%CI:1.878~19.645),neoadju-vant therapy failed(OR=3.373,95%CI:1.014~11.218),KRAS gene mutation(OR=6.245,95%CI:1.876~20.789),BRAF gene mutation(OR=9.497,95%CI:1.754~19.335)were independent risk factors for postoperative liver metastasis of stage Ⅱ~Ⅲ mid-low rectal cancer.Conclusion:Mutations in the KRAS and BRAF genes of middle are associated with poorer efficacy of neoadjuvant therapy in patients with stage Ⅱ~Ⅲ mid-low rectal cancer and are also indepen-dent risk factors for postoperative liver metastasis.

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