Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

OBJECTIVE To compare the efficacy and safety of dupilumab versus thalidomide in the treatment of refractory prurigo nodularis （PN） in adults. METHODS A retrospective analysis was conducted on the clinical data of 123 adult patients with refractory PN admitted to Wuhan First Hospital from May 2021 to June 2024. Among them， 63 patients who received dupilumab comprised the observation group and 60 patients who received thalidomide comprised the control group. Clinical efficacy indicators [Investigator Global Assessment （IGA） score， Pruritus Numerical Rating Scale （P-NRS） score， Patient-Oriented Eczema Measure （POEM） score， and Dermatology Life Quality Index （DLQI） score]， allergic biomarkers [eosinophil （EOS） count in peripheral blood and serum total immunoglobulin E （IgE） level]， psychological scores [Hospital Anxiety and Depression Scale （HADS）] before and after treatment， as well as the occurrence of adverse drug reaction during treatment， were compared between the two groups. RESULTS Before treatment， there were no statistically significant differences between the two groups in above clinical efficacy indicators， allergic biomarkers， or psychological scores （P＞0.05）. At 4， 8， 12 and 16 weeks after treatment， both groups showed significant decreases in IGA score （except for the control group 4 weeks after treatment）， IGA activity score （except for the control group 4 weeks after treatment）， P-NRS score， POEM score， DLQI score （except for the control group 4 weeks after treatment）， serum EOS count， and serum total IgE level compared with baseline （P＜0.05）； at 12 and 16 weeks after treatment， scores on both the HADS-anxiety subscale and HADS-depression subscale were also significantly lower than baseline in both groups （P＜0.05）； the observation group was significantly lower than the control group （P＜0.05）. The overall incidence of adverse events was 12.70% in the observation group， which was significantly lower than 28.33% in the control group （P＜0.05）. CONCLUSIONS Dupilumab treatment in adults with refractory PN demonstrates superior efficacy compared with thalidomide in improving skin lesions， relieving pruritus， reducing peripheral EOS counts and serum total IgE， and improving quality of life and psychological status， while showing a more favorable safety profile.

Objective To investigate the levels of gross α and gross β activities in different water types within a 40-kilometer radius around the Zhangzhou Nuclear Power Plant prior to its operation. Methods In 2018, drinking water samples were collected from the area surrounding the nuclear power plant during both the wet and dry seasons, including source water, treated water, tap water, and well water. The gross α and gross β activity concentrations were measured using a low-background α/β counter, followed by statistical analysis. Results A total of 80 water samples from different sources around the Zhangzhou Nuclear Power Plant were collected. The average gross α and gross β activity concentrations during the wet season were (0.110 ± 0.036) Bq/L and (0.643 ± 0.028) Bq/L, respectively, while those during the dry season were (0.124 ± 0.032) Bq/L and (0.624 ± 0.026) Bq/L, respectively. There were no significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for the overall sample set (P > 0.05). However, there were statistically significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for source water and well water (Z_wet = −2.005, −2.123; Z_dry = −1.943, −3.090; P < 0.05). Conclusion The radioactivity levels in different water types within various ranges around the Zhangzhou Nuclear Power Plant before its operation were determined. The measured activity concentrations were at the same level as those from previous investigations in other regions of Fujian Province.

OBJECTIVE: To evaluate the short-term effectiveness of Ilizarov technique combined with steel needle internal fixation in treating Charcot neuroarthropathy (CN) of the foot and ankle. METHODS: Between June 2020 and December 2023, 12 patients with Eichenholtz stage Ⅲ CN of the foot and ankle were treated with Ilizarov technique and steel needle internal fixation. There were 9 males and 3 females with an average age of 48.6 years (range, 19-66 years). The disease duration ranged from 1 to 16 months (mean, 6.8 months). Ankle joint involvement predominated in 7 cases, while midfoot involvement occurred in 5 cases; 3 cases presented with skin ulceration and soft tissue infection. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 31.2±9.0, 36-Item Short-Form Health Survey (SF-36)-Physical Component Summary (PCS) score was 32.6±6.8, and Mental Component Summary (MCS) score was 47.8±8.4. Postoperative assessments included wound healing, regular X-ray film/CT evaluations of fusion status, and effectiveness via AOFAS and SF-36-PCS, MCS scores. RESULTS: All operations were successfully completed without neurovascular complication. Two patients experienced delayed wound healing requiring intervention, and the others achieved primary healing. All patients were followed up 15-43 months (mean, 23.3 months). Imaging confirmed successful joint fusion within 13-21 weeks (mean, 16.8 weeks). At last follow-up, the AOFAS score was 72.5±6.4, and the SF-36-PCS and MCS scores were 63.2±8.4 and 76.7±5.3, respectively, all of which improved compared to preoperative levels, with significant differences ( P<0.05). CONCLUSION Ilizarov technique combined with steel needle internal fixation effectively restores walking function and achieves satisfactory short-term effectiveness in CN of the foot and ankle.
Humans ; Middle Aged ; Male ; Female ; Adult ; Ilizarov Technique ; Arthropathy, Neurogenic/surgery* ; Aged ; Ankle Joint/surgery* ; Treatment Outcome ; Needles ; Fracture Fixation, Internal/instrumentation* ; Steel ; Young Adult ; Foot Joints/surgery*

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective To explore the efficacy of endoscopic therapy for esophageal and gastric variceal bleeding(EGVB),investigate the risk factors for rebleeding within 1 year,and establish a predictive model accordingly.Methods A retrospective study was conducted using the clinical and follow-up data of 120 EGVB patients who underwent endoscopy at our hospital between January 2021 and December 2022.The efficacy of endoscopic therapy was analyzed,and the patients were divided into a bleeding group and a non-bleeding group based on whether rebleeding occurred within 1 year after treatment.The factors influencing rebleeding within 1 year after treatment were analyzed,and a predictive model was established using logistic regression analysis.The model's goodness of fit was evaluated using the Hosmer-Lemeshow test,and its clinical value was analyzed using the receiver operating characteristic(ROC)curve.Results The hemostasis success rate within 72 hours after endoscopic therapy was 100％in all 120 patients.Four weeks after endoscopic treatment,endoscopic reexamination showed that the complete and partial disappearance rate of varices was 75.83％(91/120),with rebleeding occurring in 10 cases(8.33％).There were 34 cases(28.33％)of cumulative rebleeding at 6 months and 63 cases(52.50％)at 1 year after endoscopic therapy.Nine patients(7.50％)died within 1 year after endoscopic therapy,all of whom were rebleeding cases.A total of 63 patients with rebleeding were included in the bleeding group,and 57 patients without rebleeding were included in the non-bleeding group.Serum sodium＜135 mmol/L(odds ratio[OR]=3.837,95％confidence interval[CI]:1.095-13.445),Child-Pugh grade C(OR=3.835,95％CI:1.137-12.935),esophageal varices degree G3(OR=5.113,95％CI:1.565-16.707),and main portal vein diameter＞12 mm(OR=5.964,95％CI:2.295-15.497)were identified as risk factors of rebleeding within 1 year after endoscopic therapy in EGVB patients(P＜0.05).The risk prediction model for rebleeding within 1 year after endoscopic therapy in EGVB patients was shown as P=1/{1+e[-(-3.815+1.345×serum sodium+1.344×Child-Pugh grade+1.786×main portal vein diameter+1.632×esophageal varices degree)]}.The Hosmer-Lemeshow x2 was 3.158(P=0.856).The area under the curve(AUC)for predicting rebleeding within 1 year after endoscopic therapy in EGVB patients was 0.815,indicating good predictive performance.Clinical validation showed that the model had an accuracy of 82.30％,with sensitivity and specificity being 81.03％and 83.63％,respectively.Conclusion Endoscopic therapy for EGVB achieves a high rate of acute bleeding control,but patients remain at risk of rebleeding.Rebleeding is associated with serum sodium＜135 mmol/L,Child-Pugh grade C,main portal vein diameter＞12 mm,and esophageal varices degree G3.The logistic regression model can effectively predict the probability of rebleeding within 1 year after endoscopic therapy.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective:To investigate the relationship between intracerebral high-density foci and progressive stroke (PS) morbidity by using dual-energy CT, which can quantify the intracerebral high-density foci of patients with acute ischemic stroke after endovascular treatment.Methods:Ninety-two patients with acute ischemic stroke who received interventional treatment in Gaozhou People′s Hospital from May 2019 to August 2020, and underwent dual-energy CT scan immediately after intervention, were analyzed. The patients were divided into PS group ( n=35) and non-PS group ( n=57) according to the National Institutes of Health Stroke Scale (NIHSS) score, and the patients whose NIHSS score increased≥4 points within 72 hours of stroke were included in the PS group, while the patients whose NIHSS score increased<4 points were included in the non-PS group. The clinical data, volume of high-density foci and CT values were compared between the 2 groups. Logistic regression analysis was used to adjust for confounding factors and screen for risk factors. The correlations of the admission NIHSS score, presence and volume of high-density lesions, maximum CT (CTmax) value and average CT (CTave) value with the onset of PS were analyzed, and the receiver operating characteristic curve was used to screen predictive indicators of PS. Results:In the PS group, the NIHSS score (18.80±8.50 vs 14.40±9.58, t=2.229, P=0.028), proportion of high-density foci [29/35(82.9%) vs 32/57 (56.1%), χ 2=6.928, P=0.008], high-density focal volume [13.23 (39.33) cm 3vs 0.76 (9.82) cm 3, U=1 440.000, P<0.001], CTmax value [80.00 (92.00) HU vs 65.00 (87.50) HU, U=1 337.000, P=0.005] and CTave value [53.48 (23.79) HU vs 45.94 (55.11) HU, U=1 345.000, P=0.004] were higher than those in the non-PS group. The NIHSS score ( OR=1.054, 95% CI 1.004-1.106, P=0.033; rs=0.255, 95% CI 0.051-0.447, P=0.014), presence of high-density foci ( OR=3.776, 95% CI 1.358-10.503, P=0.011; rs=0.274, 95% CI 0.093-0.460, P=0.008), high-density focal volume ( OR=1.026, 95% CI 1.003-1.049, P=0.027; rs=0.381, 95% CI 0.183-0.560, P<0.001), CTmax value ( OR=1.006, 95% CI 1.001-1.011, P=0.014; rs=0.292, 95% CI 0.088-0.475, P=0.005) and CTave value ( OR=1.021, 95% CI 1.007-1.035, P=0.004; rs=0.299, 95% CI 0.092-0.484, P=0.004) were all risk factors affecting PS morbidity and were positively correlated with PS morbidity. The area under the receiver operating characteristic curve of NIHSS score, high-density lesion volume, CTmax value, and CTave value to predict the onset of PS was 0.652, 0.722, 0.670 and 0.674, respectively. The volume of high-density lesions had moderate predictive value for the onset of PS. Conclusions:For AIS patients, CT examination should be performed immediately after interventional operation. The volume, CTmax value and CTave value of high-density lesions newly appeared in the ischemic area are positively correlated with the onset of PS. Quantifying the volume of high-density lesions can help to predict the onset of PS.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective This study aimed to evaluate the application of digital impression and resin model technology in removable partial dentures(RPD)for Kennedy classⅠandⅡdentition defects.Methods Patients with Kennedy classⅠorⅡdental defect were selected and grouped in accordance with the following denture production processes:digital impression/resin model/cast cobalt-chromium alloy framework group(group A),digital impression/resin model/laser printed titanium framework group(group B),alginate impression/plaster model/cast cobalt-chromium alloy framework group(group C),and alginate impression/plaster model/laser printed titanium framework group(group D),with 40 cases in each group.The final RPD was examined in place in the mouth,and the evaluation indicators included the retention force of clamp ring,the tightness of connector and base,and the accuracy of occlusion.The evaluation scores of each in-dex were used for analysis on the Kruskal-Wallis rank-sum test.Results No statistically significant difference in the score of each index was found among the four groups in RPD.Conclusion The cast cobalt-chromium alloy and laser-printed titanium framework RPD using digital impression and resin model can meet the clinical restoration requirements of patients with Kennedy classⅠandⅡdentition defects.