OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

Replantation of traumatic amputation in children has its own characteristics. This consensus primarily focuses on the issues related to the treatment of traumatically amputated limb injuries in children. Organised along a timeline, the consensus summarises domestic and international clinical experiences in emergency care and injury assessment of traumatic limb amputation limbs, indications and contraindications for replantation surgery, principles and procedures of replantation surgery, postoperative medication and management, as well as rehabilitation in children. The aim of this consensus is to propose standardise the treatment protocols for limb replantation for children therefore to serve as a reference for clinical practitioners in medical practices, and further improve the treatment and care for the traumatic limb amputations in children.

Objective:To investigate the value of conventional ultrasound features and contrast-enhanced ultrasound parameters combined with serum levels of anti-thyroglobulin antibody (TgAb) and thyroid stimulating hormone (TSH) in predicting central lymph node metastasis of papillary thyroid carcinoma (PTC).Methods:A retrospective case series study was conducted. The clinical data of 123 patients diagnosed with PTC by postoperative pathology at Shanxi Province Cancer Hospital from January 2020 to August 2023 were analyzed. According to the pathological results of cervical lymph nodes, the patients were divided into lymph node metastasis group (58 cases) and lymph node non-metastasis group (65 cases). The nodules were observed using conventional ultrasound and the signs of PTC nodules were recorded, and whether there was metastasis in the cervical lymph nodes was observed; the enhancement patterns of the target nodules were recorded using contrast-enhanced ultrasound technology, and the peak intensity (PI), time to peak (TTP) and mean transition time (MTT) were calculated; the serum TSH and TgAb levels were detected using radioimmunoassay. The results of logistic regression analysis were used to build formulas for predicting the metastasis of central lymph nodes in PTC based on conventional ultrasound features, contrast-enhanced ultrasound parameters, serum TSH level, serum TgAb level, and a combination of the 4 indicators. Using pathological results as the gold standard, receiver operating characteristic (ROC) curves of the indicators for predicting the metastasis of central lymph nodes in PTC were plotted to analyze the predictive performance of each indicator.Results:There were no statistically significant differences in baseline data between the lymph node metastasis group and the lymph node non-metastasis group (all P > 0.05). There were statistically significant differences in the proportions of patients with capsule contact, uniform echo texture, calcification and longest diameter of nodules between the two groups (all P < 0.05). The serum TSH and TgAb levels in patients of lymph node metastasis group were higher than those in patients of non-metastasis group, and the differences were statistically significant (both P < 0.05); the nodule contrast-enhanced ultrasound parameters PI, MTT and TTP in lymph node metastasis group were lower than those in non-metastasis group, and the differences were sttistically significant (all P < 0.05). Logistic regression analysis yielded the predictive formulas, conventional ultrasound features: logit ( P) = 1.017×capsule contact-1.079×calcification focus+0.899×longest diameter of nodule; contrast-enhanced ultrasound parameters: logit ( P) = 0.053×PI+0.034×MTT+0.080×TTP; contrast-enhanced ultrasound parameters combined with TSH and TgAb: logit( P)=0.062×PI+0.034×MTT+0.093×TTP-0.080×TSH-0.450×TgAb; a combination of the 4 indicators: logit( P) = 1.259×capsule contact-0.921×calcification focus+0.955×longest diameter of nodule+0.054×PI+0.016×MTT+0.099×TTP-0.300×TSH-0.516×TgAb. The area under the curve (AUC) for predicting central lymph node metastasis in PTC using conventional ultrasound features was 0.74, the AUC of contrast-enhanced ultrasound parameters was 0.76, the AUC of contrast-enhanced ultrasound parameters combined with TSH and TgAb was 0.64, the AUC of a combination of the 4 indicators was 0.87. Conclusions:The combination of conventional ultrasound features, contrast-enhanced ultrasound parameters and serum TgAb and TSH levels has good predictive value for central lymph node metastasis in PTC.

Objective:To explore the diagnostic value of ultrasound combined with tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) for peritoneal metastasis of gastrointestinal adenocarcinoma.Methods:A retrospective case series study was conducted. A total of 140 patients with gastrointestinal adenocarcinoma who were admitted to Shanxi Province Cancer Hospital from August 2021 to January 2023 were collected. Preoperative diagnosis of peritoneal metastasis was performed using tumor markers CEA and CA199 (tumor marker method) and ultrasound combined with CEA and CA199 (combined method). Using postoperative pathological results as the gold standard, the detection rate and diagnostic efficacy of the two methods for peritoneal metastasis in patients were compared.Results:Among 140 patients, there were 78 males and 62 females; the age was (59±5) years old; there were 40 cases of gastric cancer and 100 cases of colorectal cancer; pathological staging: 4 cases in stage Ⅰ, 36 cases in stage Ⅱ, 52 cases in stage Ⅲ, and 48 cases in stage Ⅳ. All patients underwent radical resection surgery, and postoperative pathological results showed that 32 cases (22.86%) had peritoneal metastasis. The detection rate of combined method for peritoneal metastasis of gastrointestinal adenocarcinoma was higher than that of tumor marker method [96.88% (31/32) vs. 78.13% (25/32)], but the difference was not statistically significant ( χ2 = 5.14, P = 0.059). The sensitivity of tumor marker method for diagnosing peritoneal metastasis of gastrointestinal adenocarcinoma was 64.00%, the specificity was 86.09%, the positive predictive value was 50.00%, the negative predictive value was 91.67%, the Kappa value was 0.379, and the area under the curve (AUC) was 0.793. The sensitivity of combined method for diagnosing peritoneal metastasis of gastrointestinal adenocarcinoma was 77.42%, the specificity was 92.66%, the positive predictive value was 75.00%, the negative predictive value was 93.52%, the Kappa value was 0.905, and the AUC was 0.985. The sensitivity and positive predictive value of combined method for diagnosing peritoneal metastasis of gastrointestinal adenocarcinoma were higher than those of tumor marker method, and the differences were statistically significant ( χ2 values were 4.06 and 13.33, both P < 0.05). Conclusions:Ultrasound combined with serum tumor markers CEA and CA199 has high diagnostic value for peritoneal metastasis of gastrointestinal adenocarcinoma.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]