Objective To establish a purification method using bacterial broth absorption to eliminate cross-reactivity in Neisseria meningitidis group ACYW135 antisera, and to verify its applicability for the detection of polysaccharide conjugate vaccines.Methods The New Zealand rabbits were immunized via auricular vein injection with meningococcal serogroups A, C, Y, and W135, respectively, with two rabbits for each group(one male and one female). Immunizations were administered every other day during the first week, totaling three immunizations, followed by continuous immunizations for a total of four weeks to prepare the baseline antisera. Cross-reactivity of the antisera was purified using repeated absorption with heterologous bacterial broth. The cross-reactivity rates between the purified and unpurified antisera and heterologous polysaccharides were compared via ELISA. The specificity of the antisera was further verified by rocket electrophoresis and rate-dependent turbidimetry. The established method was verified for specificity, specificity, reproducibility, robustness and stability.Results Before purification, significant cross-reactivity was observed, with a maximum rate of 16. 25%. After bacterial broth absorption, cross-reactivity rates for all serogroups were reduced to less than 2%, while high geometric mean titers(GMTs) of specific antibodies were maintained. Rocket electrophoresis and rate-dependent turbidimetry confirmed the absence of cross-reactions. The purified serum exhibited good specificity, and had no obvious cross-reaction with other groups of conjugate polysaccharide antigens. The intra-assay CVs of serum detection of each group ranged from 0. 96% to6. 10%, and the inter-assay CVs ranged from 3. 21% to 6. 18%, both less than 15%. The method showed good robustness with the relative error(RE) values less than 8% under varying antigen concentrations(5-15 μg/mL). The titers of the antisera remained stable over a 360-day monitoring period with no significant difference.Conclusion The established bacterial broth absorption method can effectively remove cross-reactivity in Neisseria meningitidis group ACYW135 antisera. The resulting antisera exhibit high specificity, good precision and stability, making them suitable key detection reagents for the quality control of meningococcal polysaccharide conjugate vaccines.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective: To investigate the incidence, characteristics, and influencing factors of resolution discrepancies within the minipool (MP) testing model across Chinese blood station laboratories in 2024. Methods: A nationwide, multicenter, cross-sectional study was conducted, including 334 blood station laboratories that reported nucleic acid reactive data among enzyme immunoassay non-reactive samples. Of these, 296 laboratories adopted the pool resolution model, with a total of 12 536 273 samples tested. Systematic analysis was performed on resolution data, focusing on the MP-NAT reactivity rate, the pool resolution concordance rate, and the resolution discrepancy rate. Subgroup analyses were conducted based on reagent types, viral targets, and Ct values. Potential causes were further explored through laboratory surveys and re-examination of raw amplification curves. Results: In 2024, the national average MP-NAT reactivity rate was 0.15%. The overall pool resolution concordance rate was 57.86%, which showed a gradual decline as Ct values increased across all reagents. The national average resolution discrepancy rate was 0.081‱(102/12 536 273), with 17.91%(53/296) of laboratories reporting at least one discrepancy. Nine reagent types were associated with these events, exhibiting reagent-specific patterns. For Reagent A2, the predominant discrepancy was HBV reactive pools resolving as HIV (36.36%); for Reagent D1, HBV pools frequently resolved as HCV (38.89%); and for Reagent E, the most common pattern was HIV pools resolving as HBV (48.00%). These resolution discrepancies were strongly associated with high Ct values: the median pool Ct for HBV exceeded 38, while those for HCV and HIV both exceeded 40. Investigations across 16 laboratories revealed that most discrepant samples exhibited “tailing” amplification curves, with some cases linked to cross-contamination or reagent batch-specific issues. Conclusion: While the incidence of resolution discrepancies in the MP-NAT model remains low in China, variations exist across different reagents and laboratories. These discrepancies are closely associated with low viral load, reagent performance, and laboratory operational practices.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

OBJECTIVE:To evaluate the efficacy and safety of different immunosorbent columns in the treatment of rheumatoid arthritis through a network meta-analysis,and provide evidence-based basis for clinical diagnosis and treatment.METHODS:By computer,the databases of VIP,WanFang,CNKI,PubMed,CBM,CochraneLibrary,and Web of Science were searched for published cohort studies of immunosorbent column for the treatment of rheumatoid arthritis,with a time limit until August 2024.The quality of the included randomized controlled trials was assessed using the Cochrane5.4 manual.The quality of retrospective cohort studies were evaluated via the Newcastle-Ottawa Scale(NOS).Bayesian network meta-analysis was performed using R4.1.1 software.RESULTS:A total of 13 studies were included,with a total sample size of 891 cases,and 4 immunosorbent columns were included.The results of the network meta-analysis showed that the top three orders that reduce C-reactive protein level:HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional Western medicine＞A protein adsorption column;the top three orders that reduce erythrocyte sedimentation rates:leukocyte adsorption column＞HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional western medicine;the top three orders that reduce swollen joint count:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 type adsorption column+conventional Western medicine;the top three orders that reduce tenderness joint counts:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 adsorption column+conventional Western medicine;the top three orders that reduce patients' disease activity evaluation:PH-350 adsorption column+conventional western medicine＞leukocyte adsorption column＞A protein adsorption column;the top three orders that reduce visual analogue scale scores:PH-350 adsorption column+conventional Western medicine＞A protein adsorption column＞leukocyte adsorption column;the top three orders that reduce physician's disease activity assessment:PH-350 adsorption column+conventional Western medicine＞leukocyte adsorption column＞conventional Western medicine.CONCLUSION:Based on the 13 articles,in terms of reducing C-reactive protein level,HA280 adsorption column and conventional Western medicine are the preferred choice.In terms of reducing erythrocyte sedimentation rate,swollen joint count,and tender joint count,leukocyte adsorption column is the preferred choice.In terms of reducing patient's disease activity evaluation,physician's disease activity evaluation and visual analogue scale scores,PH-350 adsorption column and conventional Western medicine are the first choice.Different immunosorbent columns can be reasonably and accurately selected according to the patient's specific conditions.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

OBJECTIVE:To evaluate the efficacy and safety of different immunosorbent columns in the treatment of rheumatoid arthritis through a network meta-analysis,and provide evidence-based basis for clinical diagnosis and treatment.METHODS:By computer,the databases of VIP,WanFang,CNKI,PubMed,CBM,CochraneLibrary,and Web of Science were searched for published cohort studies of immunosorbent column for the treatment of rheumatoid arthritis,with a time limit until August 2024.The quality of the included randomized controlled trials was assessed using the Cochrane5.4 manual.The quality of retrospective cohort studies were evaluated via the Newcastle-Ottawa Scale(NOS).Bayesian network meta-analysis was performed using R4.1.1 software.RESULTS:A total of 13 studies were included,with a total sample size of 891 cases,and 4 immunosorbent columns were included.The results of the network meta-analysis showed that the top three orders that reduce C-reactive protein level:HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional Western medicine＞A protein adsorption column;the top three orders that reduce erythrocyte sedimentation rates:leukocyte adsorption column＞HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional western medicine;the top three orders that reduce swollen joint count:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 type adsorption column+conventional Western medicine;the top three orders that reduce tenderness joint counts:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 adsorption column+conventional Western medicine;the top three orders that reduce patients' disease activity evaluation:PH-350 adsorption column+conventional western medicine＞leukocyte adsorption column＞A protein adsorption column;the top three orders that reduce visual analogue scale scores:PH-350 adsorption column+conventional Western medicine＞A protein adsorption column＞leukocyte adsorption column;the top three orders that reduce physician's disease activity assessment:PH-350 adsorption column+conventional Western medicine＞leukocyte adsorption column＞conventional Western medicine.CONCLUSION:Based on the 13 articles,in terms of reducing C-reactive protein level,HA280 adsorption column and conventional Western medicine are the preferred choice.In terms of reducing erythrocyte sedimentation rate,swollen joint count,and tender joint count,leukocyte adsorption column is the preferred choice.In terms of reducing patient's disease activity evaluation,physician's disease activity evaluation and visual analogue scale scores,PH-350 adsorption column and conventional Western medicine are the first choice.Different immunosorbent columns can be reasonably and accurately selected according to the patient's specific conditions.

Objective To develop and validate a nomogram incorporating postoperative blood pressure and other multifactorial predictors for the risk of delayed cerebral ischemia(DCI)following surgical clipping in patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods This retrospective cohort study consecutively enrolled 272 aSAH patients who underwent aneurysm clipping at the Department of Neurosurgery,Second Affiliated Hospital of Chongqing Medical University from January 2018 to January 2022.Demographic,clinical,and imaging data were collected.Predictors were screened using LASSO regression,and a multifactorial logistic regression-based nomogram was constructed.The dataset was randomly divided into training(n=190)and validation(n=82)sets at a 7∶3 ratio.Model discrimination,calibration,and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA),respectively.Results Among 272 enrolled patients,98(36%)developed DCI.Multivariate analysis identified age(OR=0.97;95%CI:0.94～0.99;P=0.036),World Federation of Neurological Surgeons(WFNS)grade(OR=1.36;95%CI:1.02～1.82;P=0.038),Fisher grade(OR=1.44;95%CI:1.01～2.05;P=0.048),and mean arterial pressure on postoperative day 2(OR=1.06;95%CI:1.03～1.09;P<0.001)as independent risk factors for DCI.The model achieved C-indices of 0.739(95%CI:0.668～0.810)in the training set and 0.760(95%CI:0.647～0.872)in the validation set.Calibration curves demonstrated high agreement between predicted and observed probabilities(mean absolute error=0.027),while DCA confirmed significant net clinical benefit at threshold probabilities of 15%～65%.Conclusion We successfully developed a predictive model incorporating age,WFNS grade,Fisher grade,and postoperative day 2 mean arterial pressure,with elevated postoperative blood pressure identified as an early critical indicator for DCI development.

Background/Aims: Gastric neuroendocrine tumors (GNETs), once rare, have become more prevalent due to the increased use of endoscopy and increased physician awareness. The clinical characteristics and long-term outcomes of GNET management were explored in this study. Methods: The clinical data of 69 patients who treated at Seoul National University Hospital between January 2013 and October 2023 were retrospectively studied. Baseline characteristics, recurrence rates, associated factors, and overall survival rates were analyzed. Results: Of the tumors, 71.0% were grade 1, 24.6% were grade 2, 1.4% were grade 3, and 2.9% were poorly differentiated. In terms of tumor type, 69.6% were type I, 1.4% were type II, and 29.0% were type III. A significant proportion of patients with grade 1 tumors received more endoscopic treatment, whereas a significant proportion of patients with grade 2 tumors underwent surgery or chemotherapy (p=0.015). The overall 5-year survival and recurrence rates were 93.8% and 7.25% (5/69), respectively. Among five patients who experienced recurrence, three had metachronous recurrence, all of which were type I; the remaining two patients exhibited distant hepatic metastasis, encompassing types I and III. The time to recurrence was 1 to 9.8 years.Margin positivity (p=0.002) and invasion deeper than the submucosal layer (p=0.007) were associated with higher recurrence rates. However, there was no significant association between recurrence and intestinal metaplasia, atrophic gastritis, or Helicobacter pylori infection. Conclusions Most patients with GNETs in this study had grade I and type I tumors, and the overall prognosis was favorable. Patients with risk factors for recurrence warrant further investigation. Those presenting margin positivity or deep invasion after resection should be closely monitored and undergo follow-up examinations, as necessary.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.