1.Differentiation and Treatment of Coronary Heart Disease from the Perspective of "Guarding the Channel Passages" Based on Circadian Rhythm
Jingjing ZHAO ; Yuanyuan CHEN ; Lanlan LI ; Xiaoqing ZHANG ; Ran ZHAO ; Shujuan XU ; Han PENG ; Lingmei LI ; Hao GUO ; Jianhua FU
Journal of Traditional Chinese Medicine 2026;67(18):1977-1981
Coronary heart disease (CHD) has a distinct circadian rhythmicity in its onset, which is closely related to the waxing and waning of qi and blood in the channel passages of the human body. Grounded in the circadian rhythm theory of "correspondence between heaven and humankind", this paper explores the pathogenic evolution rules of qi-blood disharmony, channel obstruction, interacting as cause and effect with circadian rhythm disorders in CHD. Clinically, CHD can be observed to attack in the early morning, at night, in the afternoon, and at fixed or unfixed circadian intervals. The pathogenesis rhythms at different time nodes can correspondingly reflect the susceptibility tendencies and pathological stress responses of the human body to core pathogeneses such as yang deficiency with cold congelation, yin deficiency with yang floating, qi and yin deficiency, and liver constraint with qi stagnation under specific temporal states. Treatment should be adapted to the season and time, regulating yin and yang in accordance with biological rhythms. It is recommended to regulate qi during the daytime by promoting ascending and dispersing to unblock the channel passages, and select the appropriate timing for administration to harness natural timing. At the Mao (卯) hour, yang ascends while yin descends, and taking medication at this time conforms to the ascending of yang qi. At the Wu (午) hour, the heart meridian is active, and taking medication at this time warms the channel passages and assists heart yang, which can be treated with modified Buzhong Yiqi Decoction (补中益气汤) or Shengyang Yiwei Decoction (升阳益胃汤). At night, blood should be harmonized, when the channel passages are unblocked through nourishing, restraining, and searching, with Lianmei Decoction (连梅汤) combined with Dahuang Zhechong Pill (大黄䗪虫丸). Following the temporal rhythm, the focus is put on the transitional time of day and night and the four seasons to treat disease before it arises, resonating and corresponding with the natural rhythm.
2.Comparative Genomic Analysis of Acinetobacter Baumannii from Different Sources in a Tertiary Hospital in Guangzhou
Kang LI ; Yanxian YANG ; Changbu WU ; Li SHAO ; Lanlan ZHONG ; Dingqiang CHEN ; Guobao TIAN
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(3):518-527
ObjectiveTo compare the differences between clinical and environmental sources of Acinetobacter baumannii (AB) at a tertiary hospital in Guangzhou in terms of molecular epidemiological characteristics, antimicrobial resistance, disinfectant tolerance, virulence and the distribution of related genes, as well as plasmid epidemiological characteristics; and to assess the association between environmental and clinical strains and the potential transmission risks associated with environmental contamination. MethodsA total of 118 clinical and 102 environmental AB isolates were collected from a tertiary hospital in Guangzhou between 2024 and 2025. Species identification was performed using mass spectrometry and 16S rRNA sequencing; minimum inhibitory concentrations (MICs) for eight antimicrobial agents were determined using the agar dilution method; biofilm formation capacity was assessed using the crystal violet staining method; A Galleria mellonella infection model was used to evaluate the virulence; whole-genome sequencing was employed for multilocus sequence typing (MLST), phylogenetic analysis, and studies on the distribution of resistance, disinfectant resistance and virulence genes, and plasmid screening. ResultsA total of 38 known ST types were identified among the 220 AB strains, with ST2 and ST40 being the predominant lineages. Antimicrobial susceptibility testing revealed that the clinical infection group exhibited resistance to minocycline, imipenem and other antibiotics, as well as the tolerance levels to the disinfectants triclosan and benzalkonium bromide, were generally higher than those in the environmental group (P<0.001), and the detection rates of drug resistance genes such as blaOXA-23 and adeB all exceeded 70.0%. Statistical analysis confirmed that the MIC values of TCS and BAB were significantly positively correlated with various antibiotic resistance phenotypes (P<0.05). In biofilm experiments, the proportion of strong biofilm-forming strains in the environmental group (64.7%) was significantly higher than that in the clinical infection group (11.9%;χ²=69.06, df=2, P<0.000 1), and the mortality rate of the strains increased with enhanced biofilm-forming ability. Furthermore, a total of 41 plasmid lineages and 219 insertion sequences were detected; ISs such as IS1006 and IS1007 were frequently co-occurring with resistance and virulence genes including blaOXA-23 and katA. ConclusionsThe predominant lineages of AB in this tertiary hospital were ST2 and ST40. The clinical infection group generally exhibits higher levels of antibiotic resistance and tolerance to disinfectants compared to the environmental group, while biofilm-forming ability differs : the environmental group dominates in strong biofilm formation, and the clinical group dominates in weak to moderate biofilm formation. Plasmids and ISs may be involved in the co-occurrence and dissemination control strategies and for the molecular epidemiological surveillance of multidrug-resistant bacteria.
3.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):189-207
Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
4.Effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer
Lanlan CHENG ; Jie ZHANG ; Yungai XIANG ; Lijing WAN ; Chao LIU ; Zonggang FENG ; Li TAN
Chinese Journal of Reproduction and Contraception 2025;45(7):702-708
Objective:To investigate the effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer.Methods:A retrospective cohort study was conducted to analyze 298 cycles of FET in the Department of Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University from January 2021 to June 2023. Patients were categorized into atosiban group ( n=149) and control group ( n=149) according to whether administered atosiban or not. The related indicators and clinical outcomes were compared between the two groups. Hemodynamic parameters of the uterine arteries, including bilateral uterine artery peak systolic velocity/diastolic velocity (S/D), pulsatility index (PI), resistance index (RI), and serum levels of prostaglandin F2α (PGF2α) and oxytocin were compared before and after atosiban treatment. Univariate and multivariate logistic regression analysis were applied to assess the effect of atosiban on pregnancy outcomes. The effect of atosiban on live birth rate was analyzed by age stratification. Results:The implantation rate [51.92% (135/260)], the clinical pregnancy rate [67.11% (100/149)] and the live birth rate [59.06% (88/149)] in atosiban group were significantly higher than those in control group [41.13% (102/248), P=0.015; 51.01% (76/149), P=0.005; 40.27% (60/149), P=0.001]; and the early miscarriage rate [9.00% (9/100)] was lower than that of control group [19.74% (15/76), P=0.040]. Multivariate logistic regression analysis showed that atosiban was an independent influencing factor of live birth rate ( OR=2.236, 95% CI: 1.371-3.646, P=0.001). The post-treatment right uterine artery blood flow S/D [4.61 (4.00, 5.36)], PI [1.81 (1.58, 2.05)], RI [0.79 (0.75, 0.82)], and left uterine artery blood flow S/D [4.62 (3.83, 5.61)], PI (1.84±0.38), RI [0.79 (0.74, 0.82)] were all lower than those before treatment [right S/D 4.93 (4.06, 6.04), P<0.001; PI 1.93 (1.60, 2.17), P=0.001; RI 0.80 (0.76, 0.83), P<0.001; left S/D 5.05 (4.20, 6.32), P<0.001; PI 1.95±0.43, P<0.001; RI 0.81 (0.76, 0.84), P<0.001]. Besides, the levels of PGF2α [97.01 (85.15, 109.93) ng/L] and oxytocin [41.18 (37.16, 46.78) ng/L] after treatment in atosiban group were significantly lower than those before treatment [119.71 (108.85, 129.99) ng/L, P<0.001; 51.87 (46.44, 55.54) ng/L, P<0.001). Moreover, the endometrial peristalsis waves in atosiban group were significantly less after treatment [1.00 (0.00, 2.00) times/min] than before treatment [2.00 (1.00, 3.00) times/min], and the difference was statistically significant ( P<0.001). Conclusion:Atosiban can improve uterine artery blood flow and reduce endometrial peristalsis waves in women with previous implantation failure, which increases endometrial blood perfusion. Additionally, it can also reduce the levels of PGF2α and oxytocin, and optimize the pregnancy outcome of the frozen-thawed embryo transfer.
5.Impact of umbilical cord blood mononuclear cells intrauterine perfusion on endometrial thickness and endometrial receptivity in mice with thin endometrium
Chao LIU ; Lanlan CHENG ; Li TAN
Chinese Journal of Reproduction and Contraception 2025;45(8):809-817
Objective:To investigate the therapeutic effects and underlying mechanisms of intrauterine perfusion of umbilical cord blood mononuclear cells (UCB-MNCs) on thin endometrium.Methods:SPF-grade Kunming mice aged 6-8 weeks were selected. A mouse model of thin endometrium was established by infusing 95% ethanol into the uterine cavity for a duration of 5 min. Using a completely randomized grouping method, 40 female mice with regular estrous cycles were randomly divided into four groups: untreated group (no intervention, n=10), sham-operated group (operation without modeling, n=10), experimental group (intrauterine infusion of UCB-MNCs during estrus after one estrous cycle post-modeling, n=10) and negative control group (intrauterine infusion of saline during estrus after one estrous cycle post-modeling, n=10). Following the administration of UCB-MNCs or physiological saline, all groups' uterine tissues were collected two estrous cycles later during their respective estrus phases. Hematoxylin-eosin staining was used to assess endometrial morphology, measure thickness, and count glands. Western blotting and reverse transcription real-time quantitative polymerase chain reaction were utilized to measure the relative protein and mRNA expression levels of leukemia inhibitory factor (LIF), vascular endothelial growth factor (VEGF), integrin (ITG) α V, ITG β 3 and proliferating cell nuclear antigen (PCNA) in the endometrium across different groups for intergroup comparisons. Results:The endometrial thickness and the number of glands in the untreated group [(507.32±85.66) μm, 18.67±6.66] showed no statistically significant differences compared with those in the sham-operated group [(502.78±73.26) μm, 19.33±7.73, all P>0.05]. The experimental group showed significantly increased endometrial thickness [(347.71±82.24) μm vs. (118.85±29.19) μm, P<0.001] and gland number (15.00±2.65 vs. 2.00±2.00, P=0.030) compared with the negative control group. There was no statistically significant difference in the relative protein and mRNA expression levels of LIF, VEGF, ITG α v, ITG β 3, and PCNA in the endometrium between the untreated group and the sham-operated group (all P>0.05). The relative protein and mRNA expression levels of endometrial LIF, VEGF, ITG α V, ITG β 3 and PCNA of the experimental group were all significantly higher than those in the negative control group (all P<0.05). Conclusion:Intrauterine perfusion with UCB-MNCs may promote endometrial regeneration and repair, as well as improve endometrial receptivity, through the upregulation of the expression levels of PCNA, LIF, VEGF, and ITG α V, ITGβ 3.
6.Rehabilitation effect of individual computer magnanimous therapy on patients with end-stage renal disease undergoing maintenance hemodialysis
Lanlan WU ; Junjie WANG ; Yunfang ZHANG ; Xuewei HUANG ; Yanyan SU ; Yeming LEI ; Yumin LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(8):698-705
Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.
7.Analysis of symptoms network in patients with acute type A aortic dissection and its implications in emergency triage
Mei HE ; Jie XIONG ; Sufang HUANG ; Fangfang LI ; Jin LI ; Lanlan REN ; Min CHEN
Chinese Journal of Nursing 2025;60(9):1075-1079
Objective To construct a symptom network in patients with acute type A aortic dissection(ATAAD),so as to provide theoretical basis for the screening of dissection ATAAD during emergency pre-screening triage.Methods There were 433 patients diagnosed with ATAAD during 2019 to 2023 in an emergency department of a tertiary hospital in Wuhan.Their basic information and medical records were reviewed by self-designed data questionnaire.UCINET6.0 software was used to construct a symptom network,analyze the centrality index and determine the core symptoms.Symptom distribution of patients with positive and negative blood pressure in extremities was analyzed in the further.Results The most common symptoms in patients with type A aortic dissection were chest pain(77.37%),back pain(42.96%),and sweating(29.79%).In the symptom network,chest pain had the highest degree(rs=659).The closeness of chest pain,chest tightness,shortness of breath,back pain,nausea and vomiting,limb numbness and fatigue were same(rc=93.33).Fatigue has the highest betweenness(rb=13.69).Patients with positive limbs blood pressure mainly reported chest pain(70.17%),back pain(44.96%),and nausea and vomiting(19.33%),while those with negative limb blood pressure mainly reported chest pain(63.64%),back pain(63.64%),and orosphyalgia(39.40%).Orosphyalgia had the highest degree(rs=20).Conclusion The symptoms of ATAAD are complex and varied in patients.During triage,nurses should measure the limb blood pressure when patients complained chest pain alone or when combined with other hypoperfusion symptoms,such as back pain,chest tightness,sweating,near-death sensation,and shortness of breath.Aortic dissection cannot be ruled out in patients with negative blood pressure when they had chest pain,back pain or orosphyalgia.
8.Construction and validation of nomogram model for prolonged length of stay in patients with acute cerebral infarction based on total cerebral small vessel disease burden scores
Erli ZHANG ; Lanlan HE ; Danyang LI ; Li SHEN ; Zhonghua WU ; Jun ZHANG ; Yongqiang YE
China Modern Doctor 2025;63(8):9-13
Objective To construct a nomogram model for prolonged length of stay in patients with acute cerebral infarction(ACI)based on total cerebral small vessel disease(CSVD)burden scores,and validate its effectiveness.Methods A total of 462 ACI patients admitted to the Department of Neurology of South Taihu Hospital Affiliated To Huzhou College from January 2021 to December 2023 were selected as the study subjects.According to the ratio of 7:3,patients were divided into training group of 323 cases and validation group of 139 cases.Lasso-Logistic regression was used to analyze the risk factors for prolonged length of stay in ACI patients,construct a nomogram model and validate the model using validation data.Receiver operating characteristic(ROC)curve were used to evaluate the predictive performance of the model.Results Based on the training group data,Lasso regression screened four non-zero coefficient indicators,including baseline National Institutes of Health stroke scale(NIHSS)score,age-adjusted Charlson comorbidity index(aCCI)score,neutrophil to lymphocyte ratio(NLR)and total CSVD burden score.Multivariate Logistic regression analysis showed that baseline NIHSS score,aCCI score,NLR and total CSVD burden score were independent risk factors for prolonged length of stay in ACI patients(P<0.05).Based on the above four indicators,a nomogram model was constructed.The results showed that the ROC curve area of the model predicted prolonged length of stay between training group and validation group were 0.812(95%CI:0.756-0.868)and 0.820(95%CI:0.730-0.909).Conclusion The nomogram model for prolonged length of stay in ACI patients based on total CSVD burden score has good predictive performance and can be used as a screening tool for evaluating the prolonged length of stay in ACI patients.
9.Clinical value of 18F-PSMA-1007 PET/CT combined with serum total prostate specific antigen in predicting International Society of Urological Pathology pathological grading of prostate cancer
Yunfeng BO ; Rongrong TIAN ; Lanlan BAO ; Ming ZHAO ; Jie ZHOU ; He LI ; Hailong HAO ; Enwei XU
Chinese Journal of Oncology 2025;47(2):175-182
Objective:To discuss the correlation of International Society of Urological Pathology (ISUP) pathological grading with 18F-prostate specific membrane antigen (PSMA)-1007 positron emission tomography-computed tomography (PET/CT) parameters and serum total prostate specific antigen (tPSA) in prostate cancer, and assess the clinical value of PET/CT combined with tPSA in predicting the ISUP pathological grade of prostate cancer. Methods:The correlation of ISUP pathological grade with primary parameters of PET/CT images and serum tPSA of 117 patients diagnosed with prostate cancer at Shanxi Cancer Hospital from August 2018 to February 2023 and taken 18F-PSMA-1007 PET/CT imaging were retrospectively analyzed. Univariate and multivariate logistic regressions were used to identify the independent influencing factors for ISUP pathological grading of prostate cancer. The receiver operating characteristic (ROC) curves were used to predict the efficacy between the high and low ISUP grades for prostate cancer. Results:Of the 117 patients, 20 were in ISUP Group 1, 25 in Group 2, 18 in Group 3, 32 in Group 4, and 22 in Group 5. Of these, 63 were in the low-grade group (Groups 1-3) and 54 were in the high-grade group (Groups 4-5). The tumor long diameter was 3.10 (2.05, 4.25) cm, the prostate volume was 40.11 (33.13, 51.85) cm 3, the serum tPSA was 19.71 (12.25, 42.83) ng/ml, the prostate specific antigen density (PSAD) was 0.51 (0.31, 1.01) ng·ml -1·cm -3, the maximum standard uptake value of the lesion (SUVmax) was 15.24 (10.87, 22.03), and the tumor/spleen uptake ratio (TSR) was 1.61 (1.08, 2.15) in the 117 patients. The correlation analysis displayed that the SUVmax, TSR, and tPSA were positively correlated with ISUP groups ( r=0.640, 0.619, and 0.500, P<0.01). The differences among SUVmax, TSR, long diameter, tPSA, and PSAD were statistically significant when compared among the five ISUP groups ( H=48.98, 45.63, 26.82, 33.95, and 23.81, P<0.001). The differencesin serum tPSA ( z=5.19), PSAD ( z=4.64), long diameter ( z=3.19), SUVmax ( z=5.57), and TSR ( z=5.53) of the patients between the low-grade group and the high-grade group were statistically significant ( P<0.01). In multivariate analysis, TSR ( OR=4.172, 95% CI: 2.095-8.308, P<0.001) and the serum tPSA ( OR=1.042, 95% CI: 1.014-1.070, P<0.01) were independent influencing factors for ISUP grades. ROC analysis revealed that the area under the curve for the 18F-PSMA-1007 PET/CT parameters SUVmax and TSR to predict low- or high-grade ISUP for prostate cancer was 0.800 (95% CI: 0.717-0.883) and 0.797 (95% CI: 0.713-0.881), respectively. Among the 70 patients who underwent radical prostatectomy, the postoperative recurrence rate of high-grade ISUP patients was higher than that of low-grade patients (54.8% and 25.6%, χ 2=6.21, P<0.05). Conclusions:18F-PSMA-1007 PET/CT has good application in predicting ISUP grading of prostate cancer. TSR and the serum tPSA are independent predictors for the pathological grade.
10.Role of necroptosis in paclitaxel-induced cognitive dysfunction in mice
Lanlan LIU ; Jiaxin LIU ; Zhao LI ; Mingjie WANG ; Tianyi HE ; Jinru LI ; Xin LIU ; Shuang ZHAO ; Peng LIU ; Xiuli WANG
Chinese Journal of Anesthesiology 2025;45(8):953-958
Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

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