OBJECTIVE To investigate the predictive value of prognostic nutritional index(PNI) and lymphocyte-monocyte ratio(LMR) in severe radiotherapy-induced oral mucositis(RIOM) during treatment of patients with head and neck cancer,and to construct a risk prediction model and test the prediction effect. METHODS A total of 502 patients with head and neck cancer who underwent radiotherapy were recruited from September 2021 to October 2023 in Xiangya Hospital Central South University. The participants were randomly divided into training group and validation group at a ratio of 7:3. According to whether severe RIOM occurred,they were divided into severe RIOM group and non-severe RIOM group. Univariate analysis and logistic regression analysis were used to screen the risk factors of severe RIOM. The receiver operating characteristic(ROC) curve was used to evaluate its prediction effect and R4.3.2 software was used to draw nomograms and decision curve. RESULTS The risk prediction model for patients with head and neck cancer during treatment had five factors,including the number of comorbidities(OR=2.221,95％CI=1.185-4.165),surgical history(OR=2.938,95％CI=1.393-6.198),the degree of tumor differentiation(OR=1.511,95％CI=1.090-2.094),PNI(OR=0.892,95％CI=0.852-0.934),LMR(OR=0.512,95％CI=0.254-1.030). Model formula:Y=2.102+0.413×degree of differentiation+0.798×number of comorbidities+1.078×surgical history-0.114×PNI-0.669×LMR. The validation results of the prediction model showed that the area under the ROC curve of the training group was 0.847(P<0.001),the area under the curve of the validation group was 0.808(P<0.001),and the P values of the Hosmer-Lemeshow test of the modeling group and the validation group were both greater than 0.05. The decision curve was above the reference line within most of the high-risk thresholds. CONCLUSION The risk prediction model constructed in this study has good effect,which can predict the risk of severe RIOM during radiotherapy in patients with head and neck cancer,providing the reference for taking preventive intervention measures for high-risk patients.

Objective To investigate the prevalence and severity of symptoms and to construct symptom networks in head and neck cancer patients during treatment to identify core symptoms and symptom clusters.Methods 366 patients who were hospitalized in 3 tertiary hospitals in Changsha were selected using convenience sampling from March to October 2022 and asked to complete the M.D.Anderson Symptom Inventory-Head & Neck.Exploratory factors analysis was used to extract the symptom clusters,and R packages were used to construct the symptom severity network and symptom clusters network.The centrality indexes of the networks,including strength,closeness,and betweenness,were analyzed to identify core symptoms and core symptom cluster.Results The most common symptoms in head and neck cancer patients during treatment were dry mouth(93.44％),fatigue(89.07％),loss of appetite(86.34％),and difficulty swallowing or chewing(85.79％),and the most severe symptoms were dry mouth,loss of appetite,oral or pharyngeal mucus,and difficulty swallowing or chewing.4 symptom clusters were extracted,namely oral-pharyngeal,gastrointestinal,emotional-sleep,and sickness-sensing behavioral,which could explain 67.415％of the total variance.In the symptom severity network,oral or pharyngeal mucus(rs=9.60)was a symptom with the highest strength.In the symptom clusters network,oral or pharyngeal mucus(rs=1.20),nausea(rs=1.00),fatigue(rs=1.10),and drowsiness(rs=0.97)were the symptoms with the highest strength across 4 symptom clusters.Conclusion Oral or pharyngeal mucus,nausea,fatigue,and drowsiness are the core symptoms of symptom clusters in head and neck cancer patients during treatment.Oral-pharyngeal symptom cluster is the core symptom cluster.It is recommended that clinical staff should develop interventions based on the core symptoms and symptom cluster to implement precise symptom management and improve symptom management efficiency.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Abstract OBJECTIVE To analyze the inflammation-related molecular targets of Pien Tze Huang in the treatment of hepatocellular carcinoma and to preliminary explore its mechanism. METHODS Obtain the ingredients and targets of Pien Tze Huang through TCMSP and BATMAN databases. Obtain the disease targets of hepatocellular carcinoma through Genecards, OMIM and TCGA databases. Take the intersection of compound targets and disease targets to get Pien Tze Huang’s target for the treatment of hepatocellular carcinoma. Obtain the related genes of inflammation pathway from the GSEA database, and then analyze the correlation between Pien Tze Huang’s therapeutic targets for hepatocellular carcinoma and inflammation-related genes to screen out inflammation-related targets, and explore the mechanism through GO and KEGG enrichment analysis. Then, single-factor cox analysis and LASSO regression were performed to construct related prognostic models. The 10 core targets were screened out through the protein-protein interaction(PPI) network. The model gene and the core target were intersected. The core compounds were screened out through the drug-compound-target network. Perform molecular docking verification between the core compound and the target. Construct a nomogram to assess the prognosis of patients. RESULTS Obtained 162 Pien Tze Huang targets, 522 hepatocellular carcinoma targets, 20 Pien Tze Huang therapeutic targets for hepatocellular carcinoma, and 16 inflammation-related targets. The enrichment analysis of GO and KEGG showed that their effects were mainly through biological functions such as monooxygenase activity, oxidoreductase activity, and chemical carcinogenesis-receptor activation. The ROC curve of the prognosis model calculated AUC as 0.780 in 1 year, 0.688 in 3 years, and 0.642 in 5 years, indicating that the model was reliable. The prognostic model intersects with the core target of PPI to get 5 targets: PON1, IGF2, NQO1, CCNB1 and IGFBP3. The nomogram was constructed using CCNB1, NQO1, and T staging, and its c-index was 0.726, indicating the reliability of the model. The drug-compound-target network suggested that quercetin was the core compound and targets the above two genes. CONCLUSION Pien Tze Huang’s treatment of hepatocellular carcinoma mainly uses quercetin to target CCNB1 and NQO1 to exert anti-inflammatory effects, and its prognostic model can be used to predict the survival of patients.

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

Objective To investigate the clinical features,diagnosis,treatment and prognosis of 59 patients with thrombotic thrombocytopenic purpura (TTP),therefore to improve the ability of diagnosis and treatment.Methods The clinical data of 59 patients with TTP admitted to Peking University People's Hospital from January 2004 to October 2018 were retrospectively analyzed.All the patients were clinically diagnosed,fulfilled the triad syndrome,or quinary syndrome.Laboratory data included complete blood count,blood biochemistry,immtmology,hemolysis;some patients tested the activity of ADAMTS13.The differences between groups were compared according to the prognosis.Results Among the 59 patients with TTP,21 were male and 38 were female,with an average age of 46.8 years.Fifty-five patients had the triad syndrome and 46 patients had the quinary syndrome.The platelet count and hemoglobin decreased,the percentage of erythrocyte fragmented increased,and the value or the activity of ADAMTS13 was decreased significantly.PLASMIC scores of 57 patients were between 6 and 7.All 59 patients were treated with glucocorticoid,41 patients received plasma exchange (PEX),and 28 patients survived;18 patients did not received PEX,and only 6 patients survived.There was a significant difference of the survival between the two groups (P＜0.05).Six patients were treated with rituximab and four patients survived.Conclusion The PLASMIC score can predict the activity of ADAMTS 13 well.PEX can significantly improve the survival rate of patients with TTP.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome

Objective To investigate the clinical and CT features of basal cell adenomas (BCA)of parotid gland,and to improve the understanding of the disease.Methods Clinical and CT data of 1 8 patients with BCA of parotid gland confirmed by surgery and pathology were collected.The characteristics of age,sex,clinical symptom,lesion site,number,size,shape,density and CT dualGphase enhancement of the lesions were retrospectively analyzed.Results (1)Age and sex of onset:1 2 cases(6 6.6 7%)of age stage from 30 to 5 9,5 cases (27.78%)of the elder over 60,1 case of the younger below 29,5 cases (27.78%)for males,1 3cases (72.22%)for females,the incidence ratio of male to female being 1 ︰ 2.5.(2)Clinical manifestations:there were sporadic masses in the parotid region,3 cases were accompanied by mild pain and all patients had no facial nerve symptoms.(3)Location site,number,size:23 lesions in 18 cases, of which 15 cases (83.3%)were single and 3 cases (16.7%)had multiple lesions on one side.17 lesions (73.9%)were located in superficial lobe, and 6 lesions (26.1%)were located in the deep lobe;(4)Shape and cross section diameter:the shape of the tumor was round or ellipse with wellG defined margin,13 cases (56.5%)of the round shape,10 cases (43.5%)of the ellipse;the maximum cross section diameter was (2.49±1.3 8)cm,the superficial lobe group was (2.05 ±1.02)cm,and the deep lobe group was (3.73 ±1.59)cm.The difference between the two groups on the maximum cross section diameter was significant (P＜ 0.05).(5)Density:the density of most lesions was heterogeneous.17 lesions were accompanied by central or peripheral cystic degeneration of varying degrees,of which 10 lesions with cystic regions ＞ 50% and 2 lesions with maximum transverse diameter ＜ 0.8 cm.(6)CT dualGphase enhancement:19 lesions showed obvious homogeneous or heterogeneous enhancement on the arterial phase,and persistent enhancement on the venous phase.4 lesions showed progressive heterogeneous enhancement,and the enhancement degree of venous phase was even higher than that of arterial phase.Conclusion The BCA of the parotid gland aremainly occuring in middleGaged and older women,displaying regular shape of lesions,developing to cystic degeneration easily and presenting＂fastGelevation and sustained enhancement＂or progressive enhancement patterns in the dualGphase enhanced scans.These characteristics are helpful to make a diagnosis preoperatively.

Objective To compare the early clinical efficacy of renal transplantation between extended criteria donor (ECD) and standard criteria donor (SCD). Methods Clinical data of 85 recipients undergoing renal transplantation from donation after cardiac death (DCD) were retrospectively analyzed. According to the types of donors, all recipients were divided into the ECD group (n=31) and SCD group (n=54). The level of serum creatinine (Scr), incidence of early complications and clinical prognosis within 3 months after renal transplantation were compared between 2 groups. Results No statistical significance was observed in the levels of Scr within 1 month after renal transplantation between the ECD group and SCD group (all P>0.05). At postoperative 60 and 90 d, the level of Scr in the ECD group was (189±97) and (175± 69) μmol/L respectively, significantly higher than (142±49) and (135±41) μmol/L in the SCD group (P=0.005 and 0.002). In the ECD group and SCD group, the incidence of acute rejection (AR) was 6% and 15%, the incidence of delayed graft function (DGF) was 23% and 19%, the incidence of pulmonary infection was 10% and 6%, the incidence of other early complications was 32% and 15%, respectively, no statistical significance was identified (all P>0.05). In the ECD group and SCD group, the survival rate of the recipient was 97% and 94%, the survival rate of the renal was 84% and 91%, no statistical significance was identified (all P>0.05). Conclusions Compared with the SCD, renal transplantation from ECD can achieve equivalent early clinical efficacy. In the present condition of serious deficiency of donor kidney, the application of ECD can enlarge the supply of the donor kidney.

Objective: To investigate the levels of the Twist and Vimentin proteins in oral squamous cell carcinoma (OSCC) and analyze the clinical significance of Twist and Vimentin. Methods: Eighty-five samples of OSCC and fifteen samples of normal oral mucosa were collected. Immunohistochemistry (SP method) was used to detect the expression of proteins, including Twist and vimentin. The relationship among these proteins and clinical pathological parameters was analyzed using SPSS statistical software. Results : In the normal group, 13.3% (2/15) of samples were positive for the Twist protein; this value was significantly lower than that in OSCC group (80.0%, 66/85) (χ2=26.98, P < 0.001). The expression of Twist was associated with clinical stage (χ2=5.40, P=0.02) and lymph node metastasis (χ2=8.35, P=0.006), while no correlations were found between the expression of Twist and sex (χ2=0.23, P=0.63), age (χ2= 0.31, P=0.58), location (χ2=1.46, P=0.235) or degree of differentiation (χ2=1.52, P=0.47). Additionally, 6.7% of samples (1/15) were positive for vimentin; this value was significantly lower than that in OSCC group (74.1%, 63/85) (χ2=20.71, P < 0.001). The expression of vimentin was associated with clinical stage (χ2=4.51, P=0.034) and lymph node metastasis (χ2=6.75, P=0.009), while no correlations were found between the expression of vimentin and sex (χ2=0.40, P=0.53), age (χ2=0.17, P=0.68), location (χ2=0.74,P=0.39) or degree of differentiation (χ2=4.58, P=0.10). Spearman correlation analyses showed that Twist protein expression was positively correlated with vimentin (r=0.578, P＜0.05). Conclusion Our data demonstrate that in OSCC, Twist and vimentin levels were upregulated, and Twist protein expression was positively correlated with vimentin, which indicates that both Twist and vimentin may be involved in the occurrence of OSCC.