Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

A 56-year male patient was implanted with a third generation magnetic levitation HeartCon left ventricular assist device (LVAD) for refractory heart failure through a left antero-lateral thoracotomy. Inflow cannula of the HeartCon blood pump was inserted via the left apex and outflow tract with the artificial blood vessel was sutured to the descending aorta. The operation process was smooth, the LVAD worked stably, and results of left ventricular assist was good. Implantation of HeartCon LVAD through the left antero-lateral thoracotomy is an alternative technique with less surgical complications, less trauma and satisfactory results.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective : To investigate the effect of paederosidic acid methyl ester (PAME) on postoperative learning and memory impairment in mice and its mechanism. Methods : C57BL/6J male mice were randomly divided into Sham group , operation group , operation + PAME group ( PAME group) , operation + NADPH oxidase 4(Nox4) adeno⁃associated virus overexpression group (Nox4 overexpression group) , operation + Nox4 adeno⁃associated virus no⁃laden group ( AAV no⁃load group) , and operation + PAME + Nox4 overexpression group ( PN group) . Exploratory laparotomy was performed. PAME(20 mg/kg) was administered by continuous gavage for 7 days after operation , and adeno⁃associated virus was injected into the hippocampus 28 days before operation. Morris water maze test and conditioned fear test were used to detect the learning and memory ability of mice. The expression of Nox4 protein was observed by immunofluorescence. The protein expressions of Nox4 , long chain acyl CoA synthetase 4 (ACSL4) and glutathione peroxidase 4 (GPX4) were detected by Western blot. Reactive oxygen species (ROS) and iron content were determined by spectrophotometry. Results : Compared with the Sham group , the learning and memory ability of the operation group , the Nox4 overexpression group and the AAV no⁃load group decreased , the protein expression of Nox4 and ACSL4 increased , the protein expression of GPX4 decreased , and the ROS and iron content increased. After PAME treatment , the postoperative learning and memory ability of mice was improved , and Nox4 and ferroptosis in hippocampal neurons were alleviated. Conclusion Conclusion PAME treatment can improve the learning and memory ability of postoperative mice , which may be related to the inhibition of hippocampal Nox4⁃mediated ferroptosis.

Objective:To evaluate the applicability of the Zhang′s diagnostic criteria for atopic dermatitis (AD) in adolescents and adults from southern Jiangsu.Methods:A total of 1 769 patients were collected, who were newly diagnosed with eczema or AD in departments of dermatology of 7 hospitals in southern Jiangsu from May 2019 to May 2021. A standardized survey interview was conducted with patients by dermatologists using a self-designed questionnaire, which included patient′s personal information, relevant medical history, clinical characteristics, laboratory tests, etc. Using Hanifin-Rajka criteria as the gold standard, the sensitivity and specificity of the Williams criteria, Zhang′s criteria and Japanese Dermatological Association (JDA) criteria were evaluated, separately.Results:Among the 1 769 patients, there were 759 (42.9%) males and 1 010 (57.1%) females, aged 32.2 ± 8.2 years (range, 12 - 79 years) . Pruritus was the most common clinical feature among the AD patients (883/913, 96.7%) . When using the Hanifin-Rajka criteria as the gold standard, 913 (51.6%) subjects were diagnosed with AD; the sensitivity of Zhang′s criteria reached 92.6% (845/913) , and its specificity was 73.2% (627/856) ; the sensitivity of Williams′ criteria was 87.8% (802/913) , and its specificity was 81.3% (696/856) ; the sensitivity of JDA criteria reached 96.9% (885/913) , and its specificity was 68.9% (590/856) . The consistency in the diagnosis of AD was moderate between the Zhang′s criteria and Williams criteria (Kappa = 0.61, P = 0.009) , was relatively high between the Zhang′s criteria and JDA criteria (Kappa = 0.85, P = 0.001) , and was moderate between the Williams criteria and JDA criteria (Kappa = 0.51, P = 0.013) . Conclusions:Compared with the Hanifin-Rajka criteria, the Zhang′s criteria exhibit good sensitivity and specificity for the diagnosis of AD among adolescents and adults in southern Jiangsu. However, pruritus remains important for the diagnosis of AD.

Objective:To evaluate the efficacy and safety of recombinant human tumor necrosis factor-α receptorⅡ: IgG Fc fusion protein (rhTNFR:Fc) in the treatment of drug-induced toxic epidermal necrolysis (TEN) .Methods:From 2009 to 2018, 22 patients with TEN were enrolled from 8 centers such as the Second Affiliated Hospital of Soochow University, including 10 males and 12 females, whose age ranged from 22 to 75 years. These patients were subcutaneously injected with rhTNFR:Fc at a dose of 25 mg once every 3 days for 6 - 8 consecutive sessions, and the initial dose was doubled. The drug eruption area and severity index (DASI) score and DASI improvement indices (DASI50, DASI75 and DASI90) were assessed before treatment and on days 4, 7, 10, 13, 16, 19, 22 and 25 after treatment; cytometric bead array (CBA) technology was used to detect the level of tumor necrosis factor (TNF) -α in peripheral blood and blister fluid samples. During the treatment, body temperature, rash changes, liver and kidney function of patients were monitored, and adverse reactions were recorded. Statistical analysis was carried out by using repeated measures analysis of variance, paired t test and Pearson correlation analysis. Results:Of the 22 patients, the temperature stopped rising in 20 patients without infections 24 - 72 hours after the first treatment, and returned to normal after 48 - 120 hours. Among the 22 patients, new blisters stopped appearing 24 - 48 hours after the first treatment, the skin color changed from bright red to dark purple after 48 - 96 hours, and most skin lesions subsided after 2 weeks. After 2 - 4 weeks of treatment, levels of alanine aminotransferase and aspartate aminotransferase returned to normal in 19 patients with abnormal liver function. After 4 - 13 days of treatment, levels of creatinine and urea nitrogen stopped rising in 7 patients with abnormal renal function. During the treatment, the DASI score of the 22 patients gradually decreased ( F = 532.81, P < 0.01) , from 53.64 ± 8.67 before treatment to 2.05 ± 1.21 on day 25 after treatment ( t = 26.60, P < 0.001) . On day 10 after treatment, 22 patients (100%) achieved DASI50; on day 19, 22 (100%) achieved DASI75; on day 25, 20 (90.90%) achieved DASI90. The level of TNF-α in peripheral blood of the 22 patients gradually decreased along with the extension of treatment duration, from 33.95 ± 27.90 ng/L before treatment to 2.38 ± 0.79 ng/L on day 25. Before treatment, the level of TNF-α in blister fluid of 15 patients was 111.99 ± 99.41 ng/L, and the ratio of blister-fluid TNF-α level to peripheral blood TNF-α level was 1.83 - 28.21. Before treatment, no correlation was observed between the serum level of TNF-α and DASI score in the 22 patients ( P = 0.10) , while the blister-fluid TNF-α level was positively correlated with DASI score in the 15 patients ( r = 0.59, P = 0.02) . No acute adverse reactions were observed during the treatment. All the 22 patients completed the treatment and were discharged with complete recovery. During 6 months of follow-up after discharge, no recurrence or any complication was observed. Conclusion:rhTNFR:Fc is effective and safe for the treatment of drug-induced TEN.

Objective:To investigate the safety, efficacy and survival of brentuximab vedotin (BV) monotherapy and BV combined with chemotherapy for relapsed or refractory lymphoma.Methods:A total of 47 patients with relapsed or refractory Hodgkin's lymphoma (HL) in First Medical Center of PLA general Hospital and Fourth Medical Center of PLA General Hospital from October 2011 to December 2018 were admitted, including 35 cases (BV monotherapy group) and 12 cases (BV combined with chemotherapy group); there were 8 cases of relapsed or refractory anaplastic large cell lymphoma (ALCL), 4 cases in BV monotherapy group and 4 cases in BV combined with chemotherapy group. The safety, clinical efficacy and survival of two neoplasms in different groups were compared.Results:For relapsed or refractory HL, the objective remission rate (ORR) and complete remission rate (CRR) was 67.7% (21/31) and 16.1% (5/31), and the median progressive-free survival (PFS) time was 3.5 months (1.5-24.0 months) in BV monotherapy group; ORR and CRR was 81.8% (9/11) and 27.3% (3/11), and median PFS time was 5.5 months (2.0 - 24.0 months) in BV combined with chemotherapy group; there was no statistical difference in ORR and CRR between the both groups (χ 2 = 0.788, P = 0.375; χ 2 = 0.654, P = 0.419). There were 4 cases in BV monotherapy group for ALCL, of which 3 could be evaluated for efficacy, including 1 case of complete remission (CR) and 1 case of partial remission (PR); there were 4 cases in BV combined with chemotherapy group for ALCL, of which 4 could be evaluated for efficacy, including 2 cases of CR and 2 cases of PR. The common adverse events in BV monotherapy group were anemia, leukopenia, thrombocytopenia, fever, elevated transaminase, fatigue, nausea, peripheral neuritis and cough. Grade ≥3 adverse events were mainly anemia, thrombocytopenia and leukopenia. The common adverse events of BV combined with chemotherapy group were similar to those of BV monotherapy group, and there were significant differences in bone marrow suppression (thrombocytopenia, leukopenia) between the two groups (all P < 0.05). Conclusions:The clinical efficacy of BV combined with chemotherapy is better than that of BV monotherapy in treatment of relapsed or refractory lymphoma, and the survival time is prolonged. The adverse reaction of BV combined with chemotherapy is mainly manifested in bone marrow suppression, and the safety and tolerability of patients are acceptable.

Objective To investigate whether Wnt/β-catenin signaling pathway mediating the neuroprotection of isoflurane post-conditioning in hippocampal neurons damage induced by ischemia/reperfusion injury in rats.Methods According to the randomized principle, 60 male Sprague-Dawley rats were randomly divided into five groups (12 rats in each group):sham group (group S), model group (group M), ISO+model group (group MI), ISO+model+DKK-1 group (group MDI) and model+DKK-1 group (group MD).A rat model of middle cerebral artery occlusion (MCAO) was established with 90 min ischemia followed by 24 hreperfusion.Group S was only exposed to one side of the internal carotid artery without fishing line.Isoflurane post-conditioning groups (group MI, MDI) were immediately treated with 1.5％isoflurane for 60 min at the onset of reperfusion.DKK-1 (5μg/kg) was injected intracerebroventricularly 30 min before the model established in group MDI and group MD.After reperfusion for 24 h, Longa score method was used for neurological deficit score.HE staining and Tunel fluorescence was employed to observe the morphological changes of neurons.Immunohistochemistry and Western Blot were applied to detect the expression of target protein in CA1 region.Results Compared with group S, the neurobehavioral score, the number of apoptosis and the expression of Bax and GSK-3βprotein in group M all increased (P<0.05), while the expression ofβ-catenin and Bcl-2/Bax ratio decreased (P<0.05) ;Compared with group M, the neurobehavioral score, the number of apoptosis and the expression of Bax protein were significantly decreased (P<0.05), while the expression of Bcl-2, β-catenin protein and the Bcl-2/Bax ratio were significantly increased (P<0.05) in group MI.Compared with group MI, the neurobehavioral score, the number of apoptosis, Bax and GSK-3βprotein in group MDI were significantly increased (P<0.05), while the Bcl-2, β-catenin protein expression, and Bcl-2/Bax ratio were significantly decreased (P<0.05).Conclusion Isoflurane post-conditioning may protect the hippocampus neurons against cerebral ischemic reperfusion-induced damage via the way that the Wnt/β-catenin signaling pathway regulates the expression levels of Bcl-2 and Bax proteins in rats.

Objective To provide anatomic evidence for chock-block technique used for acromioplasty.Methods Thirty cadaveric specimens of intact shoulder fixed by formaldehyde solution were used for this anatomic study.They were chosen from 15 males and 15 females and from 17 left and 13 right sides.First the specimens were dissected for observation of general morphology of the acromion.According to the Bigliani's classification,the acromions were sorted in morphology as type Ⅰ (flat),type Ⅱ (curved) and type Ⅲ (hooked).The shortest distance from the acromion to the humeral head (A-H) was measured.Then the location of subacromial impingement was observed and the thickness of the anterolateral angle was measured preoperatively.At last,acromioplasty using the chock-block technique was performed in the acromions of types Ⅱ and Ⅲ.Postoperatively,the distance A-H and the thickness of the anterolateral angle were measured again for comparison with the preoperative values.Results According to the Bigliani's classification,7 acromions were type Ⅰ,13 type Ⅱ and 10 type Ⅲ.Subacromial impact occurred only in the anterior acromions of types Ⅱ and Ⅲ.The distance A-H was 0.670 ± 0.035 cm in type Ⅰ acromions,significantly longer than the preoperative values of type Ⅱ (0.506 ±0.029 cm) and type Ⅲ (0.334 ±0.023 cm) (P ＜ 0.05),but showed no significant differences from the postoperative values of type Ⅱ (0.692 ±0.025 cm) and type Ⅲ (0.699 ±0.024 cm) (P ＞ 0.05).The anterolateral angular thickness of type Ⅰ acromions was O.413 ± 0.015 cm,significantly thinner than the preoperative values of type Ⅱ (0.607 ±0.014 cm) and type Ⅲ (0.623 ±0.025 cm) (P ＜ 0.05),but showed no significant differences from the postoperative values of type Ⅱ (0.414±0.035 cm) and type Ⅲ (0.412±0.033 cm) (P＞ 0.05).Conclusion The chock-block technique used for acromioplasty is effective because it can enlarge the supraspinatus outlet and deter impingement.