OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans ; ARNTL Transcription Factors/physiology* ; Neoplasms/therapy* ; CLOCK Proteins/physiology* ; Circadian Clocks/genetics* ; Animals ; Circadian Rhythm/genetics* ; Tumor Microenvironment ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic

Objective:To retrospectively analyze and compare the clinical effects of rigid neuroendoscopic hematoma removal and drilling irrigation drainage in the treatment of chronic subdural hematomas with mixed density on head CT, and explore the appropriate surgical methods for chronic subdural hematomas with mixed density.Methods:A retrospective case-control study was conducted to analyze the clinical data of 80 patients with CSDH with mixed density CT findings admitted to the Department of Neurosurgery of Guizhou Medical University Affiliated Hospital from January 2021 to November 2023. There were 57 males and 23 females. According to the surgical method, patients were divided into endoscopic group ( n=36) and drilling group ( n=44). Patients in the endoscopic group underwent hard neuroendoscopic hematoma removal surgery, while patients in the drilling group underwent drilling flushing and drainage surgery. Compared the surgical time, drainage time, hematoma clearance rate, length of hospital stay, markwalder neurological function grading, and activities of daily living (ADL) score between two groups 30 days after surgery. Followed up for 3 months to record the recurrence situation.Measurement data with a normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. Measurement data with a non-normal distribution were expressed as M( Q1, Q3), and rank sum test was used for inter-group comparison. Chi-square test or Fisher′s exact test was used for inter-group comparison of count data. Rank sum test was used for inter-group comparison of ordinal data. Results:The operation time, postoperative drainage time, 24-hour hematoma clearance rate, midline deviation distance and hospital stay in the endoscopic group respectively were (77.50±8.15) min, 1.00(1.00, 2, 00) d, (95.00±2.66)%, 1.00(0.00, 2.00) mm, (9.47±2.52) d. The drilling group were (44.77±6.56) min, 3.00(2.25, 3.00) d, (87.86±3.43)%, 3.00(2.00, 3.00) mm, (11.84±3.28) d, the difference was statistically significant between the two groups ( P<0.05). Comparison of long-term efficacy in the endoscopic group, the hematoma clearance rate at 30 days after operation, the ADL score at 30 days after operation, and the number of recurrence cases at 3 months after operation respectively were 99.00(97.25, 100.00)%, (88.06±7.86) points, and 1 case. The drilling group were 93.50(91.25, 95.75)%, (83.29±9.58) points and 10 cases, with statistical difference between the two groups( P<0.05). 30 day postoperative Markwalder neurological functional grading, there were 27 cases grades 0, 9 cases of grade I, and 0 cases of grade II in endoscopic surgery. In the drilling group, there were 24 cases, 15 cases, and 5 cases, respectively. The difference between the two groups was statistically significant ( P<0.05). Conclusions:Compared with drilling and drainage irrigation surgery, neuroendoscopic treatment of mixed density chronic subdural hematoma takes a relatively long time, but the hematoma clearance rate is higher, the hospitalization time is shorter, the postoperative recovery is faster and the recurrence rate is lower. Neuroendoscopic therapy has unique advantages and may be more suitable for the treatment of mixed density CSDH.

Objective To evaluate the clinical efficacy of electroacupuncture at acupoints distributed on conception vessel(CV)and governor vessel(GV)in treating ischemic stroke(AIS)complicated with dysphagia and explore its potential mechanism.Methods A total of 120 patients diagnosed with AIS complicated with dysphagia at Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from December 2020 to December 2023 were enrolled and randomly divided into an observation group and a control group,with 60 patients per group.The control group received conventional swallowing training,while the observation group received additional electroacupuncture at acupoints distributed on CV and GV.The treatment lasted for 4 weeks.After 1 month of treatment,clinical efficacy was assessed,and the changes in Standardized Swallowing Assessment(SSA)scores,National Institutes of Health Stroke Scale(NIHSS)scores,hyolaryngeal mobility(thyroid cartilage anterior/superior displacement,hyoid bone anterior/superior displacement),and KubotaWater Swallowing Test scores were observed.Cerebral microcirculation parameters and the Chinese version of the Eating/Drinking Quality of Life(EDQoL)questionnaire were also compared.Safety and adverse events were evaluated.Results(1)The total effective rate in the observation group was 95.00%(57/60),compared to 76.67%(46/60)in the control group,demonstrating statistically superior therapeutic efficacy in the observation group(P＜0.05).(2)After treatment,both groups showed significant improvements in SSA scores and NIHSS scores(P＜0.05),with the observation group exhibiting markedly better enhancement in both SSA and NIHSS scores compared to the control group,showing statistically significant differences(P＜0.05).(3)After intervention,significant improvements were observed in anterior displacement of thyroid cartilage,superior displacement of thyroid cartilage,anterior displacement of hyoid bone,and superior displacement of hyoid bone in both groups(P＜0.05).The observation group outperformed the control group in all these laryngeal kinematic parameters with statistically significant differences(P＜0.05).(4)Both groups demonstrated significant improvement in Kubota Water Swallowing Test scores after treatment(P＜0.05),with the observation group displaying statistically greater improvement than the control group(P＜0.05).(5)Cerebral arterial parameters including peak systolic velocity(Vs),mean velocity(Vm),and resistance index(RI)were significantly improved in both groups after treatment(P＜0.05).The observation group showed superior enhancement in these cerebrovascular hemodynamic indices compared to the control group(P＜0.05).(6)Significant improvements in EDQoL scores were observed in both groups after treatment(P＜0.05),with the observation group achieving statistically greater improvement than the control group(P＜0.05).(7)The total incidence of adverse reactions was 1.67%(1/60)in the observation group versus 11.67%(7/60)in the control group,indicating a statistically significant lower adverse event rate in the observation group(P＜0.05).Conclusion Electroacupuncture at acupoints distributed on CV and GV effectively alleviates dysphagia and neurological impairment,improves hyolaryngeal mobility and cerebral microcirculation,enhances quality of life,and reduces adverse events such as aspiration pneumonia in AIS patients complicated with dysphagia.

Sarcopenia is an age-related syndrome characterized by progressive and widespread loss of skeletal muscle mass and/or decline in muscle function.Its incidence increases year by year with aging and is influenced by multiple factors,including genetic background,lifestyle,nutritional status,and chronic diseases.Recent studies have revealed a significant correlation between sarcopenia and chronic coronary syndromes(CCS),not only in terms of the frequency of occurrence but also the se-verity of the conditions.Moreover,sarcopenia and CCS share common pathogenic mechanisms,en-compassing various pathophysiological processes such as chronic inflammation,oxidative stress,apop-tosis,and insulin resistance.This article aimed to review the current research progress on comorbidity relationship between sarcopenia and CCS,explore their shared pathophysiological basis,and discuss their impacts on clinical prognosis.

Objective:To clarify the changes of intrahepatic ultrasound hemodynamics before and after hepatic artery thrombosis (HAT) after liver transplantation (LT), providing early warning and anticoagulation guidance to clinicians.Methods:The clinical data of patients who underwent liver transplantation at Zhongshan Hospital of Fudan University between June 2006 and October 2022 were retrospectively analyzed, 47 patients with a diagnosis of HAT confirmed by DSA (digital subtraction angiography) were included in the HAT group, and 71 patients without vascular complications were included in the non-HAT group. Differences in peak flow velocity (PSV), resistance index (RI), and portal vein velocity (PVV) were compared between the two groups. Logistic regression analysis was used to determine the relationship between postoperative PSV decline and HAT occurrence, while ROC curve were used to determine the critical value and evaluate the diagnostic efficacy. Patients with HAT were divided into well-treatment group and poor-treatment group according to whether the blood flow was restored after multiple surgeries or thrombolytic treatments. The changes of early intrahepatic hemodynamics after surgical or thrombolytic therapy were compared between the two groups.Results:①A decrease in PSV of the transplanted hepatic artery was measured 1 d before HAT, and PSV<0.39 m/s predicted thrombus formation with a sensitivity of 0.70, specificity of 0.86, and the AUC was 0.83. ②After treatment, PSV in the HAT group increased immediately, approaching the normal level on the 2nd day. In the well-treatment group, PSV and PVV reached normal levels on the first day after treatment, which were significantly higher than the corresponding values in the poor-treatment group ( P=0.030, 0.021). Conclusions:In the early stage after liver transplantation, a PSV<0.39 m/s is related to the occurrence of HAT thrombosis 1 d later. A significant increase in PSV on the first day after treatment indicates a good treatment response, and there is no need for further DSA re-examination or increasing the number of thrombolysis.

Objective:To explore the effect of esketamine on inflammatory cytokines and myocardial injury markers in children undergoing living-donor liver transplantation (LT).Methods:Considering the inclusion criteria, 50 children with biliary atresia were selected for living donor LT. They were equally randomized into two groups of control (C) and esketamine (E) (25 cases each). Esketamine 0.5 mg/kg was administered to group E during induction and continued at a dose of 0.5 mg·kg –1·h -1 after an induction of anesthesia. Group C provided the same dose of 0.9% sodium chloride injection during induction and then continued to pumping until the end of the procedure. Basic profiles of two groups were recorded. Hemodynamic parameters, such as heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP), were monitored at 5 min of anesthesia induction (T 0), 30 min of anhepatic phase (T 1), immediately after repercussion (T 2), 30 min of neohepatic phase (T 3) and end of surgery (T 4) in both groups. Central venous blood samples were collected at T 0, T 1, T 3 and T 4. Serum levels of cardiac troponin I (cTnI), creatine kinase isoenzyme-MB (CK-MB) ,tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured. The incidence of adverse cardiac events, postoperative mechanical ventilation time, ICU stay and hospitalization length were compared. Results:As compared with T 0, mean arterial pressure (MAP) at T 2 declined markedly in group E [(48.6±12.7) mmHg (1 mmHg=0.133 kPa) vs (55.6±10.7) mmHg, P<0.001] and C [(39.3±8.0) mmHg vs (53.2±9.4) mmHg, P<0.001 ] ;As compared with T 0, the TNF-α and IL-6 spiked at T 3 in group C [169.0 (207.1) ng/L vs 43.8 (26.4) ng/L, (132.63±51.75) ng/L vs (51.79±17.83) ng/L, P<0.001] and E [78.5 (138.8) ng/L vs 43.8 (26.4) ng/L, (87.44±32.17) ng/L vs (51.79±17.83) ng/L, P<0.001 ] ; In group C, the concentration of myocardial injury markers CK-MB and cTnI rose at T 3/T 4 compared with T 0[T 3 vs T 0: 5.7 (5.4) μg/L vs 4.0 (3.5) μg/L, 0.09 (0.08) μg/L vs 0.02 (0.02) μg/L; T 4 vs T 0: 5.3 (5.0) μg/L vs 4.0 (3.5) μg/L, 0.07 (0.08) μg/L vs 0.02 (0.02) μg/L, P<0.001 ]. In group E, the levels of CK-MB and cTnI were higher at T 3/T 4 than those at T 0[T 3 vs T 0: 7.0 (5.0) μg/L vs 4.6 (2.1) μg/L, 0.06 (0.09) μg/L vs 0.03 (0.04) μg/L; T 4 vs T 0: 5.4 (4.9) μg/L vs 4.6 (2.1) μg/L, 0.03 (0.06) μg/L vs 0.03 (0.04) μg/L; P<0.001]. Compared with group C, the MAP of E rose at T 1/T 2/T 3 [(58.8±10.3) mmHg vs (53.3±8.6) mmHg, P=0.048; (48.6±12.7) mmHg vs (39.3± 8.0) mmHg, P=0.003; (55.8±7.4) mmHg vs (51.5±7.3) mmHg, P=0.044]. Compared with group C, TNF-α and IL-6 decreased in E at T 3/T 4[T 3: 78.5 (138.8) ng/L vs 169.0 (207.1) ng/L, P=0.010; (87.44±32.17) ng/L vs (132.63±51.75) ng/L, P=0.017. T 4: 62.3 (118.3) ng/L vs 141.3 (129.2) ng/L, P=0.001; (74.34±26.38) ng/L vs (100.59±30.40) ng/L, P=0.002]. Compared with group C, cTnI decreased in E at T 3/T 4[0.06 (0.09) μg/L vs 0.09 (0.08) μg/L, P=0.014; 0.03 (0.06) μg/L vs 0.07 (0.08) μg/L, P=0.003]. Compared with group C, the mechanical ventilation time in group E decreased [195 (120) min vs 315 (239) min, P<0.001]. Compared with group C, the incidence of severe hypotension [16%(4/25) vs 48% (12/25), P=0.015 ], bradycardia [12% (3/25) vs 36 % (9/25), P=0.047 ], myocardial ischemia [4 % (1 /25) vs 24 % (6/25), P=0.042 ] and premature ventricular contractions [0 vs 4 %(1/25), P=0.312 ] decreased in group E. Conclusion:Intraoperative dosing of esketamine may suppress inflammatory reactions and alleviate perioperative myocardial injury in children undergoing living-donor LT.

Esketamine is a spin isomer of ketamine,which has the triple effect of sedation,analge-sia and amnesia,and is superior to ablative ketamine in terms of efficacy,controllability.It has been widely used in anesthesia,emergency and critical care in Europe and America,and is mostly used for sedation,analgesia and antidepressant in China.Esketamine is used in cardiac surgery to maintain stable hemodynam-ics,reduce the secretion of inflammatory factors and relieve postoperative pain.Its sympathomimetic effect allows it to be used for the induction of anesthesia in patients with hemodynamic instability and acute heart attack.This paper reviews the recent advance in the clinical value and limitations of esketamine in the perio-perative period of cardiovascular surgery and provides a reference for clinicians to use esketamine in the perioperative period of cardiovascular surgery.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Acute and critical illnesses pose a serious threat to people's lives and health,causing great difficulties for doctors to rescue them.As an important part of traditional Chinese medicine(TCM)clinical medicine,emergency medicine of TCM has formed its own unique and complete theoretical system and accumulated rich clinical experience in the long-term struggle against diseases by the unremitting efforts of generations of doctors.As a well-known contemporary expert in TCM clinical emergency treatment,Professor Liu Qingquan has been deeply involved in the front line of clinical work,and creatively proposed the theory of three states and three principles differentiation,providing a rapid and effective core idea for the treatment of contemporary acute and critical patients with TCM.