Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

PURPOSE: Percutaneous ilio-sacral screw (ISS) insertion using conventional C-arm fluoroscopy has been a widely employed technique for pelvic posterior ring fixation, particularly in developing regions. However, this approach presents technical challenges, leading to a high malposition rate. We introduced a new method for ISS insertion without additional equipment or software and suggested whether it could reduce the malposition rate and operating time. METHODS: This is a retrospective cohort study. The study included all patients who underwent percutaneous ISS fixation between January 2020 and December 2022. Patients treated with open reduction or other types of implants were excluded. The patients were divided into 2 groups based on the screw insertion method: Group A utilized the traditional dual-plane adjustment method, while Group B received the newly introduced method. In all cases, conventional C-arm fluoroscopy was the sole guidance during the surgical procedure. Malposition rate, radiation exposure, and operating time were compared between groups. Post-operative CT scans were used to assess screw accuracy using the Smith grading method. The Student's t-test or the Mann-Whitney U test was chosen for comparing the quantitative variables based on the normality test results. The Chi-squared test was utilized for comparing qualitative variables. RESULTS: A total of 72 patients with pelvic posterior ring disruption treated with percutaneous ISS under conventional fluoroscopy guidance were included in this study. Among them, 32 patients were in Group A and 40 patients were in Group B. In Group B, the average operation duration per screw was 33 min with 29 fluoroscopy applications, which was significantly lower than that in Group A (44 min, p < 0.001, 38 times, p < 0.001, respectively). Furthermore, the post-operative CT scan revealed that only 10.7% (6/56) of screws in Group B were inappropriately positioned according to the Smith criteria. CONCLUSION The novel method introduced in this study demonstrated a reduction in both malposition rates and operating time compared to the traditional dual-plane adjustment method. Precise pre-operative CT planning in conjunction with conventional fluoroscopy could establish this method as a widely applicable technique for percutaneous ISS fixation.
Humans ; Fluoroscopy/methods* ; Retrospective Studies ; Bone Screws ; Female ; Male ; Tomography, X-Ray Computed/methods* ; Sacrum/diagnostic imaging* ; Middle Aged ; Operative Time ; Adult ; Fracture Fixation, Internal/methods* ; Ilium/diagnostic imaging* ; Aged

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective:To explore the influence of substance abuse history on anxiety and depression of male prisoners during their imprisonment, and its relationship with violent behavior.Methods:A questionnaire survey was conducted among 1 455 prisoners from October to November 2019.Self-administered personal substance abuse history questionnaires were used to collect the information on substance abuse (alcohol, tobacco, and drug use). The generalized anxiety scale (GAD-7) and patient health questionnaire (PHQ-9) were used to investigate anxiety and depression.All subjects were divided into substance abuse group ( n=871) and non substance abuse group ( n=584) according to whether they had a history of substance abuse or not.SPSS 21.0 software was used for statistical analysis.The statistical methods were t-test, chi square test and Logistic regression analysis. Results:(1)The scores of GAD-7 ((4.95±5.88) vs (3.35±5.33), t=-5.407, P<0.01) and PHQ-9 ((6.69±6.50) vs (4.48±5.73), t=-6.821, P<0.01) scales in the substance abuse group were higher than those in the no-substance abuse group.(2)Somatic disease( β=0.700, OR=2.014, 95% CI=1.599-2.538, P<0.05), history of alcohol abuse( β=0.434, OR=1.543, 95% CI=1.176-2.025, P<0.05), history of tobacco abuse( β=0.387, OR=1.473, 95% CI=1.154-1.880, P<0.05), age ≤ 45( β=0.372, OR=1.450, 95% CI=1.118-1.881, P<0.05) were the risk factors of anxiety among prisoners.Somatic disease( β=0.686, OR=1.986, 95% CI=1.581-2.496, P<0.05), history of tobacco abuse( β=0.488, OR=1.629, 95% CI=1.286-2.063, P<0.05), age ≤ 45( β=0.484, OR=1.622, 95% CI=1.260-2.089, P<0.05), history of alcohol abuse( β=0.344, OR=1.410, 95% CI=1.073-1.854, P<0.05) were the risk factors of depression among prisoners.(3) Years of education ≤ 9 years( β=0.900, OR=2.459, 95% CI=1.855-3.261, P<0.05), age ≤ 45( β=0.788, OR=2.199, 95% CI=1.690~2.860, P<0.05), unmarried( β=0.683, OR=1.980, 95% CI=1.421-2.759, P<0.05), history of alcohol abuse( β=0.308, OR=1.361, 95% CI=1.053-1.758, P<0.05), history of drug abuse( β=0.557, OR=1.745, 95% CI=1.055-2.885, P<0.05) were risk factors for violent behavior of prisoners. Conclusion:The history of substance abuse may be a risk factor for anxiety and depression of prisoners during their imprisonment.Alcohol and drug abuse are both factors influencing the occurrence of violent behavior.

Objective:To evaluate the efficacy and safety of bendamustine monotherapy in Chinese patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) .Methods:This prospective, multicenter, open label, single-arm, phase Ⅱ study investigated bendamustine’s efficacy and safety in Chinese patients with R/R B-NHL. A total of 78 patients with B-NHL in 11 hospitals in China from March 2012 to December 2016 were included, and their clinical characteristics, efficacy, and survival were analyzed.Results:The median age of all patients was 58 (range, 24-76) years old, and 69 (88.4% ) patients had stage Ⅲ/Ⅳ disease. 61 (78.2% ) patients were refractory to previous treatments. Patients received a median of 4 (range, 1-10) cycles of bendamustine treatment. The overall response rate was 61.5 (95% CI 49.8-72.3) % , the median response duration was 8.3 (95% CI 5.5-14.0) months, and the complete remission (CR) rate was 5.1 (95% CI 1.4-12.6) % . In the full analysis set, median progression-free survival (PFS) and median OS were 8.7 (95% CI 6.7-13.2) months and 25.5 months (95% CI 14.2 months to not reached) , respectively, after a median follow-up of 33.6 (95% CI 17.4-38.8) months. Lymphopenia (74.4% ) , neutropenia (52.6% ) , and leukopenia (39.7% ) , thrombocytopenia (29.5% ) and anemia (15.4% ) were the most common grade 3-4 hematologic adverse events (AE) . The most frequent non-hematologic AEs included nausea (43.6% ) , vomiting (33.3% ) , and anorexia (29.5% ) . Univariate and multivariate analysis showed that <4 cycles of bendamustine treatment was a poor prognostic factor for PFS ( P=0.003) , and failure to accept fludarabine containing regimen was a poor prognostic factor for OS ( P=0.009) . Conclusion:Bendamustine monotherapy has good efficacy and safety in the treatment of patient with R/R B-NHL.

ObjectiveTo explore the effect of flipped classroom mode in the clinical probation teaching for undergraduate mental health students， so as to expand the new mode of clinical teaching in psychiatry department. MethodsA total of 85 undergraduate psychiatric students from Xinxiang Medical University in 2016 were selected. All participants were divided into experimental group （n=43） and control group （n=42） according to the random number table method. The flipped classroom clinical teaching mode was adopted to experimental group， and the traditional practice mode for control group. The probation lasted for 12 weeks. Theoretical knowledge of symptomology， psychiatric clinical skills （OSCE）， doctor-patient communication ability（SEGUE） and clinical thinking ability were assessed at the end of probation. ResultsAfter the probation， students in experimental group obtained higher scores in theoretical knowledge， clinical skills， doctor-patient communication ability and clinical thinking ability compared with control group. The differences were statistically significant ［（33.08±1.72） vs. （32.06±2.33）， （51.61±2.12） vs. （48.32±2.86）， （18.14±1.98） vs. （14.62±2.15）， （91.26±14.13） vs. （82.40±10.89）， t=2.307， 6.034， 3.230， 7.846， P<0.05 or 0.01］. ConclusionApplying the flipped classroom mode into the clinical probation teaching for mental health undergraduate students may help to improve students' theoretical knowledge level and clinical operation ability， faciliate doctor-patient communication， and have a positive impact on their clinical thinking ability.

Objective: To explore the short-term efficacy and prognosis of palliative surgical treatment for malignant bowel obstruction (MBO) caused by peritoneal metastasis of colorectal cancer (mCRC). Methods: A retrospective cohort study was conducted. The inclusion criteria for patients were as follows: (1) primary colorectal cancer; (2) massive peritoneal metastasis; (3)obstructive site located below Treitz ligament by imaging; (4) obstruction refractory to conservative treatment; (5) estimated rese survival time more than 2 months; (6) patients and their families had strong willingness for operation; (7) surgical treatment included stoma/bypass and debulking surgery. In accordance with the above criteria, clinicopathological data of 46 patients undergoing palliative surgery at Peking University Gastrointestinal Cancer Center, Unit III from January 2016 to October 2018 were retrospectively collected. Postoperative symptomatic relief rate, morbidity of complication within 30 days, complication classification (Clavien-Dindo classification), mortality and survival after operation were analyzed. Kaplan-Meier method was used to evaluate survival and Cox regression analysis was used to identify prognostic factors. Results: Among 46 patients, 30 were male and 16 were female with median age of 63 (19-87) years; 23 patients received stoma/bypass surgery (stoma/bypass group), and 23 cases received tumor debulking surgery (debulking group). The overall symptom relief rate was 76.1% (35/46), while symptom relief rate in the debulking group was 91.3% (21/23), which was significantly higher than 60.9% (14/23) in the stoma/bypass group (χ²=4.301, P=0.038). Postoperative complications occurred in 25 patients. The complication rate was 52.2% (12/23) in the debulking group and 56.5% (13/23) in the stoma/bypass group, without statistically significant difference (χ²=0.088, P=0.767). Morbidity of complication beyond grade III was 8.7% (2/23) and 13.0% (3/23) in the debulking group and stoma/bypass group respectively, without statistically significant difference (χ²=0.224, P=0.636). Four patients died within 30 days after operation, 2 (8.7%) in each group. Twenty-four patients underwent 1-8 cycles of chemotherapy ± targeting therapy (regimens: CapeOX ± Bevacizumab, FOLFOX/FOLFIRI ± Bevacizumab/Cetuximab), including 10 cases in the stoma/bypass group and 14 cases in the debulking group. Two patients of debulking group received postoperative radiotherapy and chemotherapy (50.6 Gy/22 f, with concurrent oral capecitabine). Till the last follow up of April 2019, 34 patients died (34/46, 73.9%) with a median overall survival time of 6.4 months, and the 6-month and 1-year survival rate was 54.5% and 29.2% respectively. The median survival time in the debulking group was significantly longer than that in the stoma/bypass group (11.5 months vs. 5.2 months, χ²=5.117, P=0.024). The median survival time of the 35 patients with symptomatic relief after operation was significant longer than that of 11 patients without relief (7.1 months vs 5.1 months, χ²=3.844, P=0.050). Multivariate analysis showed stoma/bypass surgery (HR=2.917, 95%CI:1.357-6.269, P=0.006) and greater omental metastasis (HR=4.060, 95%CI:1.419-11.617, P=0.009) were independent risk factors associated with prognosis of patients with MBO caused by peritoneal mCRC. Conclusions For patients of MBO caused by peritoneal mCRC, tumor debulking surgery may achieve higher symptom relief rate and prolong survival. Greater omental metastasis indicates poor prognosis.

To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM.Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015. The expressions of miR-221/222 in serum and in sorted CD138 positive plasma cells were detected by qRT-PCR, and the relative expression of miR-221/222 (Δct) was compared between the groups. Serum levels of miR-221 before and after treatment were compared in both remission group (=22) and refractory group (=13) in MM patients, and its correlation with serum level of β-MG was assessed using Pearson's correlation analysis.Serum levels of miR-221/222 in MGUS and MM groups were significantly higher than those in control group (all<0.01), while miR-221/222 levels in plasma cells were significantly lower in MGUS and MM groups than those in the control group (<0.05 or<0.01). No significant difference in miR-221/222 levels in serum and plasma cells was observed between MGUS group and MM group (all>0.05). There was no correlation between miR-221/222 levels in serum and plasma cells (=0.024 and -0.127, all>0.05), but miR-221 levels were correlated with miR-222 levels in both serum and plasma cells (=0.534 and 0.552, all<0.01). Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUCs) of serum miR-221/222, plasma cell miR-221/222 in diagnosis of MGUS/MM were 0.968, 0.976, 0.801 and 0.727, respectively. There was no significant difference in serum level of miR-221 among MM patients with different paraprotein isotypes (>0.05), but serum level of miR-221 in patients with relapsed MM was higher than that in patients with newly diagnosed MM (<0.01). Compared with the patients with MGUS or MM stageⅠ and Ⅱ, patients with MM stage Ⅲ were of higher serum levels of miR-221 (<0.01). Serum level of miR-221 decreased after chemotherapy in the remission group (=51.5,<0.01), but such decrease was not observed in the refractory group (=67.5,>0.05). Serum level of β-MG was positively correlated with serum level of miR-221 (=0.524,<0.01).miR-221/222 in serum and plasma cells may be biomarkers for early diagnosis of MGUS, and are helpful for diagnosis and efficacy evaluation of MM.
Biomarkers ; analysis ; blood ; Bone Marrow ; chemistry ; Disease Progression ; Humans ; MicroRNAs ; analysis ; blood ; Monoclonal Gammopathy of Undetermined Significance ; genetics ; physiopathology ; Multiple Myeloma ; chemistry ; genetics ; physiopathology ; Myeloma Proteins ; analysis ; Paraproteinemias ; genetics ; physiopathology ; Prognosis ; Recurrence

Objective To observe clinical curative effect of the FLAG regimen combined donor lymphocyte infusion after granulocyte colony stimulating factor(G‐CSF) mobilization(G‐DLI) ,for the acute myeloid leukemia (AML) of allogeneic Peripheral blood hematopoietic stem cell trans‐plantation (allo‐HSCT) after recurrence of hematology .Methods For the patients with recur‐rence after allo‐HSCT ,giving the FLAG regimen chemotherapy when the WBC dropped to the lowest point ,followed by giving G‐DLI that infusion peripheral blood stem cell from the original donors ,to observe curative effect and survival situation .And searched the literature review through the PubMed etc .Results Through FLAG regimen combined G‐DLI ,3 cases of relapse after transplan‐tation again obtained complete remission (CR) .Case 1 :disease‐free survival (DFS) was 13 month and overall survival(OS) was 23 months after G‐DLI .The patient has been the central recurrence and remission in bone marrow ,he was dead after 23 months due to multipleorgan function failure .He occurred Ⅱ acute GVHD in Skin and Ⅰ acute GVHD in liver after G‐DLI and obtained effective control ,not chronic GVHD .Case 2 :DFS and OS were 12 months and 13 months ,as bone marrow relapse again and giving up treat‐ment ,so died a month later .Respectively ,he has limitations chronic GVHD in skin after G‐DLI .Case 3:DFS was 16 months after G‐DLI since the disease‐free survival ,had limitations GVHD in skin that was control for given small dose of immunosuppressive drugs .Conclusion Joint FLAG scheme and G‐DLI may be one of the effective treatment of postoperative recurrence of allo‐HSCT .

Objective:To explore the effects of miR-27a on the phenotype and cytokine secretion in LPS-stimulated dendritic cells.Methods:Murine bone marrow-derived dendritic cells were transfected with miR-27a mimics and negative control mimics,and then stimulated by LPS for 24 hours.Dendritic cells exposed to LPS were collected for analysis of the DC immunophenotype by flow cy-tometry and supernatants were collected to determine cytokine lever.Moreover,the capability of stimulating allogeneic CD4 T+cell prolif -eration was measured by MLR ( mixed lymphocyte reaction) .Results: The levels of MHCⅡ, CD80, and CD86 were significantly increased in LPS-stimulated dendritic cells when compared with imDC ( P<0.001).Transfection with miR-27a mimics resulted in sig-nificantly lower expression levels in levels of MHCⅡ,CD80,and CD86 (P<0.001).For cytokine secretion,transfection with miR-27a mimics enhanced IL-10 production (P<0.01) and reduced the production of IL-12 (P<0.05).For MLR,transfection with miR-27a mimics suppressed allogeneic CD4+T cell proliferation.Conclusion: MiR-27a may play critical roles in regulating the maturation process and cytokine secretion in LPS-stimulated dendritic cells.