Malignant proliferating liver cancer cells possess the ability to detect and respond to various body signals, thereby facilitating tumor growth, invasion, and metastasis. One crucial mechanism through which hepatocellular carcinoma (HCC) cells interpret these signals is crosstalk. Within liver cancer tissues, cancer cells engage in communication with hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), and immune cells. This interaction plays a pivotal role in regulating the proliferation, invasion, and metastasis of HCC cells. Crosstalk occurs in multiple ways, each characterized by distinct functions. Its molecular mechanisms primarily involve regulating immune cell functions through the expression of specific receptors, such as CD24 and CD47, modulating cell functions by secreting cytokines like transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), and mediating cell growth and proliferation by activating pathways such as Wnt/β-catenin and Hedgehog. A comprehensive understanding of the mechanisms and interactions within crosstalk is essential for unraveling the pathogenesis of HCC. It also opens up new avenues for the development of innovative therapeutic strategies. This article reviews the relationship between crosstalk and the progression of HCC, offering insights and inspiration for future research.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Hepatic Stellate Cells/physiology* ; Disease Progression ; Signal Transduction/physiology* ; Transforming Growth Factor beta/metabolism* ; Cell Proliferation ; Hedgehog Proteins/metabolism* ; Tumor-Associated Macrophages ; Platelet-Derived Growth Factor/metabolism* ; Cell Communication/physiology*

Objective To investigate the effects of meropenem and amikacin on gut microbiota diversity and composition in a neonatal rat model of necrotizing enterocolitis(NEC).Methods Neonatal SD rats(1～2 d,weighing 5～10 g,both sexes)were subjected to establish a NEC model through artificial formula feeding,hypoxic-cold stress,and lipopolysaccharide(LPS)gavage.The rats were randomly divided into normal control group(Group C,n=12),NEC group(Group N,n=20),meropenem intervention group(Group M,n=20),and amikacin intervention group(Group A,n=20).Following modeling,Group M and Group A received intraperitoneal injections of meropenem(125 mg/kg)or amikacin(468 mg/kg),twice daily for 3 consecutive days.Groups C and N were administered an equal volume of normal saline.At the end of the intervention,colonic contents or fecal samples were collected.The gut microbiota structure was analyzed using 16S rDNA high-throughput sequencing.Bioinformatics analysis was performed using the QIIME2 platform.Alpha diversity was evaluated using Chao1,Shannon,and Simpson indices.Beta diversity was assessed based on Bray-Curtis distance through principal coordinate analysis(PCoA)and non-metric multidimensional scaling(NMDS).Venn and UpSet plots were generated to visualize the composition and overlap of operational taxonomic units(OTUs).Linear discriminant analysis effect size(LEfSe)was applied to identify differentially abundant taxa across groups.Results High-throughput 16S rDNA sequencing showed that the N group had significantly lower 3 indices of α diversity than the C group(P<0.01),that is,a Chao1 index from 230 to 40,a Shannon index from 1.65 to 0.85,and a Simpson index from 0.65 to 0.42.After antibiotic intervention,both the M group and A group obtained obvious increases in the Chao1 index than the N group(P<0.001),with a greater increase observed in the M group than in the A group(P<0.05).However,neither antibiotic group exhibited notable improvements in the Shannon index or Simpson index compared with the N group(P>0.05).Venn and UpSet analyses revealed that the M group had the highest number of unique OTUs(283),while the A group shared the most OTUs(63)with the C group.PCoA and NMDS analyses indicated that the microbial structure of the A group was closer to that of the C group,with better clustering.Taxonomic composition and LEfSe analysis demonstrated that the N group was enriched with potentially pathogenic taxa such as Escherichia coli B2 and Klebsiella under the phylum Proteobacteria,while beneficial bacteria including Lactobacillaceae and Bifidobacteriaceae(phylum Firmicutes)were significantly reduced,indicating severe dysbiosis.In contrast,the A group exhibited a significant increase in beneficial bacteria and a structural tendency toward ecological recovery.The M group,however,was enriched with various conditionally pathogenic and environmentally associated genera,displaying a microbial configuration notably deviating from a healthy state.Conclusion Meropenem and amikacin exhibit differential regulatory effects on the intestinal microbiota in the context of NEC.Amikacin demonstrates superior efficacy in restoring microbial stability and levels of beneficial bacteria,whereas meropenem,although effective for early infection control,warrants caution due to its potential long-term impact on the gut microbiome.

Objective:To explore the efficacy and safety of bortezomib or thalidomide combined with recombinant human erythropoietin(rhEPO)in the treatment of multiple myeloma(MM).Methods:A total of 80 patients with MM who were treated in the Second People's Hospital ofWuhu from January 2013 to December 2018 were selected as the research subjects,and they were divided into bortezomib group(n=40)and thalidomide group(n=40)by the simple randomization method.The bortezomib group received bortezomib regimen combined with rhEPO therapy,and the thalidomide group was given thalidomide regimen combined with rhEPO therapy,and all patients were treated for 3 courses with every 3 weeks as a course of treatment.The clinical efficacy after 3 courses of treatment,and tumor-related biochemical indicators[lactate dehydrogenase(LDH),β 2-microglobulin([3 2-MG),vascular endothelial growth factor(VEGF),apoptosis inhibitory protein Survivin],bone marrow-related indicators[serum M-protein,bone marrow plasma cells,hemoglobin(Hb)]and coagulation function indicators[activated partial thromboplastin time(APTT),prothrombin time(PT),plasminogen activator inhibitor(PAI),total circulating microparticles(TMPs)]before treatment and after 3 courses of treatment were compared between the two groups of patients.The occurrence of adverse reactions during the treatment in the two groups of patients was recorded.Results:After 3 courses of treatment,the ORR rate of 92.5％in bortezomib group was higher than 90.0％in thalidomide group,but the difference was not statistically significant(P＞0.05).The levels of LDH,[3 2-MG,VEGF,Survivin,serum M-protein,bone marrow plasma cells,APTT,PT,PAI and TMPs in the two groups after 3 courses of treatment were significantly lower or shorter than those before treatment,and the above indicators in bortezomib group were significantly lower or shorter than those in thalidomide group(P＜0.05).After 3 courses of treatment,the expression level of Hb in the two groups was significantly higher than that before treatment,and the Hb level in bortezomib group was significantly higher than that in thalidomide group(P＜0.05).During the treatment process,the incidence rates of adverse reactions in bortezomib group were significantly lower than those in thalidomide group(P＜0.05).Conclusion:Thalidomide regimen or bortezomib regimen combined with rhEPO has similar clinical efficacy on MM,but bortezomib regimen combined with rhEPO is more prominent and safer on improving tumor-related biochemical indicators,bone marrow-related indicators and coagulation status in patients with MM.

Objective To explore the anatomical basis and clinical effect of radical styloid process bone(membrance)flap pedicled with the recurrent branch of radial artery to styloid process for repairing carpal scaphoid fracture.Methods The equal lengths of the radial styloid process in 25 adult radial specimens were measured.A latex-perfused male adult upper limb specimen was dissected to observe the course and distribution of the recurrent branch of radial artery to styloid process.The clinical data of 15 patients with carpal scaphoid fracture repaired by transposition and implantation of radical styloid process bone(membrance)flap pedicled with the recurrent branch of radial artery to styloid process were retrospectively analyzed,and the therapeutic effect was analyzed.Results The length of the radial styloid process measured on 25 radial specimens was 11 to 16 mm.Dissection of the latex-perfused male adult upper limb specimens revealed:the radial artery in the snuffbox emitted a thicker dorsal carpal branch to the ulnar side at(1.2±0.2)cm below the styloid process,and then sent a branch proximally back to the styloid process.The fracture line of 15 patients disappeared after surgery,with a fracture healing rate of 100%,and a mean healing time of 12 weeks;the Krimmer wrist joint function score showed that 6 cases were excellent,7 cases were good,and 2 cases were acceptable,with excellent and good rate of 86.7%;patients had lower postoperative pain visual analogue scale scores compared with those before surgery,the difference was significant(P<0.05).Conclusion Measuring the radial styloid process of the physical specimen and observing the course and distribution of the recurrent branch of radial artery to styloid process in adult upper limb specimens can guide the formulation of surgical plan for the treatment of carpal scaphoid fractures in clinic.The transposition and implantation of radical styloid process bone(membrance)flap pedicled with the recurrent branch of radial artery to styloid process can effectively promote fracture healing,and reduce the risk of delayed healing,which has good postoperative recovery of wrist joint function and definite clinical effect in the treatment of carpal scaphoid fractures.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.
Child ; Humans ; Spinal Cord Injuries/complications* ; Spinal Cord

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans ; Dermatitis, Atopic/drug therapy* ; Quality of Life ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans ; Dermatitis, Atopic/drug therapy* ; Quality of Life ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca²⁺ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.