OBJECTIVES: To identify immunosuppressive neutrophil subsets in patients with prostate cancer (PCa) and construct a risk prediction model for prognosis and immunotherapy response of the patients based on these neutrophil subsets. METHODS: Single-cell and transcriptome data from PCa patients were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Neutrophil subsets in PCa were identified through unsupervised clustering, and their biological functions and effects on immune regulation were analyzed by functional enrichment, cell interaction, and pseudo-time series analyses. Lasso-Cox regression was utilized to construct a prognostic risk model based on the immunosuppressive neutrophil subsets, and survival analysis and ROC curve analysis were used to compare the prognosis of PCa patients with high and low risks stratified using this model. The relationship of the prognostic risk model with PCa immune infiltration and immune response was evaluated using CIBERSORT and TIDE scores. RESULTS: PCa tissues showed a significantly greater proportion of infiltrating neutrophils than the adjacent normal tissues (P<0.05). PCa-associated neutrophils could be clustered into two independent cell subsets: Neu_1 and Neu_2. Neu_2 cells exhibited highly enriched immunoregulatory functions and were highly differentiated and mature, with upregulated immunosuppressive cytokines such as TGFB1, ITGB2, and LGALS3. Based on the genetic characteristics of Neu_2 cell subsets, the prognostic risk model was constructed. The patients in the high-risk group identified by the model had a shorter biochemical recurrence time (P<0.05) and a higher proportion of Tregs and M2-TAMs cell infiltration (P<0.05) with a higher risk of immune rejection and poorer immune response scores. CONCLUSIONS PCa-associated neutrophils are highly heterogeneous. The prognostic risk model constructed based on the immunosuppressive neutrophil Neu_2 subset can effectively predict both the survival outcomes and immune response of PCa patients.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Prognosis ; Neutrophils/immunology* ; Immunotherapy

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

OBJECTIVE: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type ⅢA and ⅢB open tibial fractures. METHODS: A retrospective study was performed on 22 patients with Gustilo type ⅢA and ⅢB open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type ⅢA fractures and 13 were type ⅢB fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. RESULTS: The wound area was 21.0-180.0 cm ² (mean, 57.82 cm ²) before operation, and it was 1.2-27.0 cm ² (mean, 6.57 cm ²) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). CONCLUSION Nice knot technique can be used in wound closure of Gustilo type ⅢA and ⅢB open tibial fractures effectively, which is easy to operate.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Cicatrix ; Retrospective Studies ; Treatment Outcome ; Tibial Fractures/surgery* ; Wound Healing ; Fracture Fixation, Internal/methods* ; Fractures, Open/surgery*

Objective Liver cancer is the second leading cause of tumor-related death.The efficacy of local thermal ablation is comparable to surgical resection for the early hepatocellular carcinoma(HCC),and the ablation technique is minimally invasive,repeatable,and has a low complication rate.However,early recurrence((2 years)is the main cause of death after HCC ablation,but there is still a lack of accurate and reliable prediction models for early recurrence.Therefore,this survey intended to construct prediction models for early recurrence of HCC after ablation by using preoperative gadoxetic acid disodium-enhanced magnetic resonance(MR)images data combined with radiomics methods,evaluate and verify their predictive efficacy.To explore the application value of contrast-enhanced MRI imaging before ablation in the prognosis assessment of HCC patients,and to provide reliable data and theoretical basis for clinical treatment decisions.Methods A retrospective study was performed on 120 patients with HCC who underwent ablation and all the patients were underwent contrast-enhanced MRI examination within 1 month.A total of 1318 radiomic features were extracted from each patient by using preoperative T2-weighted sequence(T2WI)images of contrast-enhanced MRI.After feature selection,six machine learning algorithms would be used for construction of models and comparison.Finally,Logistic regression analysis was used to establish a clinical model,a radiomics model and a combined model which included the above risk factors and radiologic features.The nomogram was constructed based the combined model to evaluate the differentiation,accuracy and clinical benefit.Results Five radiomic features most closely related to early recurrence were identified and selected for model construction.The radiomic model had effective predictive performance,with AUC of 0.80 in the training sets.Two clinical risk factors associated with early recurrence,including tumor number and peritumoral hypodensity on the hepatobiliary phase,were selected to established a clinical-radiological-radiomics(CRRM)model,with AUC as high as 0.92 in the validation sets.The nomogram of CRRM model was constructed and the calibration curves indicated the goodness of fit.Decision curve analysis further confirmed the clinical usefulness of CRRM model.Conclusion The radiomics model of preoperatively contrast-enhanced MRI-T2WI image features was identified be effective to predict HCC early recurrence.In contrast,the CRRM model could be used as a more comprehensive and superior tool to predict individual probability of early recurrence.Patients at high risk of early recurrence could be identified and the appropriate and effective preoperative treatments could also be taken,to improve the prognosis and long-term survival rate of HCC patients the individualized treatment strategies should be formulated.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective:To establish the ultra high performance liquid chromatography (UPLC) fingerprints of Mume flos at different flowering stages; To provide reference for the quality research of Mume flos.Methods:The fingerprints of Mume flos were established by UPLC method, and the common peaks were identified by high performance liquid chromatography high resolution mass spectrometry (LC-MS). Chemometrics analysis was carried out with the fingerprints' common peak area of plum blossom at different flowering stages as a variable. Semiquantitative analysis of changes in flavonoids and phenolic acids in Mume flos at different flowering stages was conduct using peak area calculation method.Results:Totally 31 common peaks were identified in the fingerprints of plum blossom medicinal materials at different flowering stages and 9 components were identified. Clustering analysis (HCA) and principal component analysis (PCA) both classified plum blossom medicinal herbs at different flowering stages into three categories. Among them, there were significant differences between the groups at the bud stage, blooming period, and final flowering period, while the differences between the groups at blooming period and final flowering period were relatively small. The orthogonal partial least squares discriminant analysis (OPLS-DA) screened 16 different components with VIP>1.0. The contents of phenolic acids in different flowering stages were as follows: bud stage>blooming period>final flowering period, while the contents of flavonoids were as follows: blooming period>final flowering period>bud stage.Conclusions:This method is simple and reliable, and can provide reference for the quality evaluation of plum blossom medicinal materials at different flowering stages.

Objective To evaluate the clinical efficacy,safety,and potency ratio of microwave ablation(MW A)combined with percutaneous osteoplasty(POP)for the treatment of flat bone metastases.Methods A total of 57 patients with flat bone metastases complicated by intractable pain,who underwent MWA combined with POP(combination therapy)or only POP(pure POP therapy)at the Zhongshan Municipal People's Hospital of China between January 2016 and January 2023,were enrolled in this study.The combination therapy group had 36 patients and the pure POP therapy group had 21 patients.Visual analog scale(VAS),Oswestry Disability Index(ODI),quality of life assessment scale(QOL)were used to evaluate the preoperative and the postoperative different period efficacy,and the results were compared between the two groups.The procedure-related complications in both groups were recorded.Results The technical success rate in the 57 patients was 100％,and no serious postoperative complications occurred.The mean follow-up time was(4.7±1.3)months(range of 3.4-7.2 months).The preoperative and the postoperative one-day,one-week,one-month and 3-month VAS scores in the combination therapy group were(7.39±1.09)points,(6.53±1.17)points,(1.94±0.70)points,(1.11±0.66)points and(1.39±0.59)points respectively,which in the pure POP therapy group were(7.52±1.01)points,(6.81±0.66)points,(3.38±0.65)points,(2.33±0.56)points and(2.52±0.50)points respectively.One week after operation,the VAS scores in the combination therapy group and the pure POP therapy group were decreased by(5.44±1.32)points and(4.14±0.96)points respectively.The differences in the postoperative one-week(t=-7.62,P＜0.01),one-month(t=-7.28,P＜0.01)and 3-month(t=-7.58,P＜0.01)VAS scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month ODI scores in the combination therapy group were(44.33±2.91)points,(44.08±2.82)points,(15.92±3.04)points,(14.00±2.39)points and(16.08±3.61)points respectively,which in the pure POP therapy group were(45.67±3.03)points,(45.14±2.80)points,(22.38±3.09)points,(19.76±2.99)points and(22.10±3.10)points respectively.One week after operation,the ODI score in the combination therapy group was decreased by(28.42±4.23)points,which in the pure POP therapy group was decreased by(23.29±4.28)points.The differences in the postoperative one-week(t=-7.50,P＜0.01),one-month(t=-7.37,P＜0.01)and 3-month(t=-6.51,P＜0.01)ODI scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month QOL scores in the combination therapy group were(24.69±3.92)points,(26.06±3.05)points,(38.67±3.00)points,(40.25±3.42)points and(39.58±3.99)points respectively,which in the pure POP therapy group were(24.43±3.53)points,(26.76±3.05)points,(32.81±2.17)points,(33.95±2.68)points and(31.19±4.27)points respectively.One week after operation,the QOL score in the combination therapy group was increased by(13.97±4.88)points,which in the pure POP therapy group was increased by(8.38±4.50)points.The differences in the postoperative one-week(t=8.34,P＜0.01),one-month(t=7.56,P＜0.01)and 3-month(t=7.18,P＜0.01)QOL scores between the two groups were statistically significant.The mean operation cost in the combination therapy group was 10 480.43 Chinese yuan,which was higher than that in the pure POP therapy group.Conclusion For the treatment of flat bone metastases,both pure POP therapy and MWA combined with POP therapy are clinically safe and effective,which can significantly relieve pain and improve quality of life.Compared with pure POP therapy,the MWA combined with POP therapy is more effective but its medical cost is more expensive.