ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective To explore the effect of acyl-CoA synthetase short-chain family member 3(ACSS3)gene on the proliferation of human large cell lung cancer cells(NCI-H460)using CRISPR/Cas 9 gene editing technology.Methods The expression of ACSS3 was detected by Western blot.ACSS3-targeting sgRNAs were designed,and a CRISPR/Cas 9 knockout vector was constructed and transfected into NCI-H460 cells.The transfected cells were selected with puromycin based on vector-carried resistance.ACSS3-knockout monoclonal cell strains were established by limited dilution method and then expanded in culture.Knockout efficiency was confirmed by Western blot.Cell proliferation was assessed using MTT and colony formation assays.Results The expression of ACSS3 was significantly elevated in NCI-H460 cells as compared with human normal lung epithelial cells BEAS-2B(P＜0.05).No ACSS3 protein was detected in the knockout monoclonal strain,indicating successful generation of ACSS3-knockout NCI-H460 cells.Compared with the control cells transfected with empty vector,the proliferation and colo-ny formation ability were inhibited in NCI-H460 cells with ACSS3 knockout(P＜0.05).Conclusions The ACSS3-knockout NCI-H460 cell strain was successfully established,which provides a foundation for further study on the role of ACSS3 in lung cancer.

Objective To evaluate the application efficacy of structured symptom intervention program in patients with chronic kidney disease(CKD)during the peri-dialysis period.Methods A non-simultaneous control study was conducted on 151 peri-dialysis outpatients having not yet initiated dialysis and being followed up who were subjected with convenience sampling from Department of Nephrology of Second Affiliated Hospital of Army Medical University from April to September 2024.According to the time period of their visits,the patients who visited from April to June 2024 were assigned into a control group(n=75),and those from July to September 2024 into an experimental group(n=76).The control group received conventional symptom intervention(telephone symptom reporting+health education),while the experimental group received the intervention as the control group and a structured symptom intervention program covering 4 evidence-based modules:symptom identification,assessment,intervention,and outcome.The efficacy of above treatments was evaluated before and at 3 months after intervention.Dialysis symptom index was used to assess the degree of symptom distress and the number of symptoms.MOS 36-Item Short Form Health Survey(SF-36)was employed to evaluate the quality of life.The differences in clinical indicators and endpoint events were compared between the 2 groups after intervention.Results The experimental group obtained more significant reduction in the total score of symptom distress than the control group(P=0.021).After intervention,the number of symptoms was decreased in both groups(P<0.001),but no statistical difference was observed between the groups.The score of mental health dimension in SF-36 was obviously improved in the experimental group(P=0.004),which was notably better than that in the control group(P=0.033).The experimental group exhibited significantly higher prealbumin level than the control group(P=0.019),and stable albumin level,which was significantly decreased in the control group(P=0.035).The incidence of endpoint events was remarkably lower in the experimental group than the control group(P=0.028).Conclusion The structured symptom intervention program implements intervention through a closed-loop symptom module,which can effectively alleviate the symptom distress of patients during the peri-dialysis period,improve mental health and reduce the short-term risk for endpoint events.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.

Objective:To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) versus functional electrical stimulation (FES) in the treatment of post-stroke complex regional pain syndrome. Methods:The randomized controlled study included 60 patients with post-stroke complex regional pain syndrome who received treatment at the Wenzhou TCM Hospital of Zhejiang Chinese Medical University from July 2021 to February 2023. These patients were divided into an rTMS group ( n = 30) and an FES group ( n = 30) using a random number table method. Patients in the rTMS group were treated with rTMS, while those in the FES group were treated with FES. All treatments were performed once daily for 8 consecutive weeks. The clinical efficacy, total active movement score of the fingers, Fugl-Meyer assessment scale score, Activity of Daily Living score, modified Barthel Index score, shoulder joint range of motion, and safety were compared between the two groups. Results:The total response rate in the FES group was 86.7% (26/30), which was significantly higher than 83.3% (25/30) in the rTMS group ( Z = 0.09, P = 0.93). After treatment, there were no significant differences between the two groups in terms of total active movement score of the fingers and Fugl-Meyer assessment scale score ( P = 0.244, 0.262). No significant differences were found between the two groups in MBI score and ADL score (both P > 0.05). There was also no significant difference in shoulder joint range of motion between the two groups ( P > 0.05). Conclusion:Both rTMS and FES are highly effective for post-stroke complex regional pain syndrome. They can improve upper limb function, enhance daily living abilities, and remodel neurological functions of the brain.

OBJECTIVE To evaluate the comprehensive value of four first-line combination immunotherapy for unresectable hepatocellular carcinoma， and provide a reference for determining the optimal clinical treatment decision for unresectable hepatocellular carcinoma. METHODS R4.2 software was used for network meta-analysis to obtain the effect values of the efficacy and safety indicators of four combination therapies [atezolizumab combined with bevacizumab （AB）， sintilimab combined with bevacizumab biosimilars （SB）， camrelizumab combined with apatinib （CA）， durvalumab combined with tremelimumab （DT）]. Combined with the efficacy， safety and economic indicators， the categorical based evaluation technique （M-MACBETH） was used to establish the value tree. At the same time， the comprehensive value scores of four therapies were calculated， and sensitivity analysis was performed to evaluate the robustness. RESULTS In terms of prolonging median overall survival， the advantage order of the four therapies was ranked as SB， CA， AB and DT. In terms of extending median progression-free survival， the advantage order of the four therapies was CA， SB， AB and DT. In terms of safety， the order of advantages was DT， AB， SB and CA. In terms of economy， the order of advantages was CA， SB， AB and DT. The comprehensive scores of SB， CA， AB and DT were 67.11， 57.77， 52.53 and 42.59 points， respectively. The results of the sensitivity analysis showed that the ranking results of comprehensive value for four regimens were robust. CONCLUSIONS Among the four first-line immune combination therapies for unresectable hepatocellular carcinoma， SB is the optimal treatment regimen， followed by CA， AB and DT.