Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

ObjectiveTo explore the efficacy and potential neural mechanisms of individualized precision rehabilitation combining multimodal neuromodulation technologies under the guidance of multidisciplinary team (MDT)-based whole process dynamic assessment in a patient with large-area cerebral infarction who responded poorly to conventional rehabilitation. MethodsA 38-year-old male patient presented with hemiplegia and complete aphasia following large-area cerebral infarction in the left fronto-temporo-parietal lobe and basal ganglia due to arterial dissection. Under the MDT framework, the patient underwent six months of inpatient rehabilitation and one month of outpatient follow-up. Multimodal assessments were performed at multiple time points using diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), three-dimensional gait analysis and 128-channel electroencephalogram (EEG) monitoring, combined with standardized scales, such as Chinese Rehabilitation Research Center Standard Aphasia Examination (CRRCAE), Loewenstein Occupational Therapy Cognitive Assessment (LOTCA), simplified Fugl-Meyer Assessment (FMA) and modified Barthel Index (MBI). The rehabilitation protocol integrated conventional therapies with multimodal interventions, including multi-target transcranial magnetic stimulation, brain-computer interface (BCI)-driven robotic hand training and task-oriented virtual reality upper limb training. ResultsAfter intervention, the patient showed significant improvements: LOTCA score increased by 16 points, CRRCAE subscale scores improved by 60% to 90%, total FMA score increased from 20 to 54, FMA-Balance reached 12, and MBI improved from 40 to 91. DTI revealed an increase in global fiber tract count, elevated fractional anisotropy in the corpus callosum and right corticospinal tract, and significantly increased amplitude of low-frequency fluctuations and regional homogeneity in specific brain regions on fMRI. Event-related desynchronization dynamically decreased during BCI training, and three-dimensional gait parameters showed overall improvement. ConclusionFor patients with large-area stroke who respond inadequately to conventional rehabilitation, an individualized precision rehabilitation system based on MDT whole-process dynamic assessment and integrating multimodal neuromodulation with conventional therapy can effectively enhance cognitive, language, motor functions and activities of daily living. Neuroimaging and electrophysiological findings suggest that the mechanism may involve promoting neural fiber remodeling and modulating regional brain activity.

Objective:To analyze the differences in the variation characteristics of peripheral blood immune cell subsets and their mitochondrial mass between schizophrenia patients (SZ) and healthy individuals (HC).Methods:The selected subjects included 487 schizophrenic patients aged 20 to 70 (schizophrenia group), who were diagnosed and treated in Quanzhou Third Hospital from February 2021 to October 2021, and 175 healthy individuals (control group) of the same age and during the same period. Their age, gender, years of education, and years of illness were collected. The psychopathological symptoms of the patients were assessed by PANSS (Positive and Negative Syndrome Scale). The flow cytometry was used to analyze the percentage, the absolute count of T cells and their subsets in peripheral blood, the mitochondria mass (MM) and the variation in the single-cell mitochondria mass (SCMM) of these T cells. To determine whether the mitochondrial mass parameters were consistent with clinical manifestations, the test data collected from 32 first diagnosed patients were compared before and after treatment. The analysis methods involved in the study mainly include the Human Lymphocyte Mitochondrial Function Analysis System (HLMFAS) used to calibrate of the mitochondrial test results, the SPSS software used for statistical analysis, and the flowjo software used for the t-SNE dimension reduction analysis of the flow cytometry data.Results:The SCMM value of CD8 +T cells (abbreviated as CD8 +) in SZ was significantly higher than those values in HC ( P<0.001). The threshold of the ROC curve of the SCMM(CD8 +) between SZ and HC was greater than 95.84. SZ showed a significantly higher SCMM(CD8 +) value than HC across all age groups (20-70 years). For the 32 first diagnosed patients, the test data were monitored before and after treatment. The results indicated a positive linear correlation between the SCMM of CD8 + and the PNASS data ( P<0.05,ρ (Spearman)>0). Conclusion:Schizophrenic patients have abnormal mitochondrial metabolism in their peripheral immune cells with an up-regulated SCMM, indicating possible damage to the mitochondria.

Objective:To analyze the differences in the variation characteristics of peripheral blood immune cell subsets and their mitochondrial mass between schizophrenia patients (SZ) and healthy individuals (HC).Methods:The selected subjects included 487 schizophrenic patients aged 20 to 70 (schizophrenia group), who were diagnosed and treated in Quanzhou Third Hospital from February 2021 to October 2021, and 175 healthy individuals (control group) of the same age and during the same period. Their age, gender, years of education, and years of illness were collected. The psychopathological symptoms of the patients were assessed by PANSS (Positive and Negative Syndrome Scale). The flow cytometry was used to analyze the percentage, the absolute count of T cells and their subsets in peripheral blood, the mitochondria mass (MM) and the variation in the single-cell mitochondria mass (SCMM) of these T cells. To determine whether the mitochondrial mass parameters were consistent with clinical manifestations, the test data collected from 32 first diagnosed patients were compared before and after treatment. The analysis methods involved in the study mainly include the Human Lymphocyte Mitochondrial Function Analysis System (HLMFAS) used to calibrate of the mitochondrial test results, the SPSS software used for statistical analysis, and the flowjo software used for the t-SNE dimension reduction analysis of the flow cytometry data.Results:The SCMM value of CD8 +T cells (abbreviated as CD8 +) in SZ was significantly higher than those values in HC ( P<0.001). The threshold of the ROC curve of the SCMM(CD8 +) between SZ and HC was greater than 95.84. SZ showed a significantly higher SCMM(CD8 +) value than HC across all age groups (20-70 years). For the 32 first diagnosed patients, the test data were monitored before and after treatment. The results indicated a positive linear correlation between the SCMM of CD8 + and the PNASS data ( P<0.05,ρ (Spearman)>0). Conclusion:Schizophrenic patients have abnormal mitochondrial metabolism in their peripheral immune cells with an up-regulated SCMM, indicating possible damage to the mitochondria.

Objective:To explore the predictive value of the systemic immune inflammation index (SII) for the risk of bone metastases in patients with newly diagnosed prostate cancer (PCa).Methods:From Jun. 2012 to Jul. 2019, the clinical features of 308 patients were retrospectively analyzed. For the baseline clinical data of the patients with newly diagnosed PCa, the median age was 71(65-76) years, there were 59(19.2%) patients with a positive digital rectal examination (DRE). In addition, the median serum total prostate-specific antigen (tPSA), prostate volume (PV) and prostate-specific antigen density(PSAD)were 60.55(23.55-100.00) ng/ml, 39.35(28.29-56.66)ml and 1.27(0.58-2.52)ng/(ml·cm 3), respectively. There were 33(10.7%)patients with prostate biopsy Gleason score≤6, 115(37.3%)patients with a Gleason score=7 and 160(52.0%)patients with a Gleason score≥8. The T clinical stage also obtained, including 21(6.8%)diagnosed as T 1 stage, 87(28.2%)T 2 stage, 65(21.1%)T 3stage, 135(43.9%)T 4 stage. SII was calculated by the formula platelet×neutrophil/lymphocyte, and the median(interquartile range)of SII was 458.60(300.42-727.11)/L. According to the results of bone scanning, the patients were divided into bone metastasis(146, 47.4%)and a non-bone metastasis groups(162, 52.6%). The differences in the baseline clinical characteristics between the two groups were analyzed. The risk factors of bone metastasis were analyzed by univariate and multivariate logistic regression analysis. The diagnostic efficiency of the risk factors were evaluated by receiver operating characteristic(ROC)curve. Results:The median(interquartile range)of SII was 564.78/L(333.85-961.93/L)in patients with bone metastasis which were higher than those without bone metastasis 413.01(267.63-601.79)/L( P<0.001). The median(interquartile range)of tPSA were 97.79(48.20-119.10)ng/ml in bone metastasis group and 32.56(17.89-72.70)ng/ml in non-bone metastasis group ( P<0.001). The median(interquartile range)of PSAD were 1.91(0.97-3.55)ng/(ml·cm 3)and 0.90(0.45-1.77)ng/(ml·cm 3)in these two groups( P<0.001), respectively. In bone metastasis group, there were 132(90.4%)patients with a positive DRE, yet there were only 117(72.2%) patients with a positive DRE in the other group ( P<0.001). There were 7(4.8%)patients with prostate biopsy Gleason score≤6, 50(34.2%)patients with a Gleason score=7 and 89(61.0%)patients with a Gleason score≥8 in bone metastasis group. There were 26(16.1%)patients with prostate biopsy Gleason score≤6, 65(40.1%)patients with a Gleason score=7 and 71(43.8%)patients with a Gleason score≥8 in non-bone metastasis group ( P<0.001). There were statistically significant difference between the two groups in T clinical stage( P<0.001). In bone metastasis group, there were 2(1.4%)T 1 stage, and 19(13.0%)T 2 stage, 25(17.1%)T 3stage, and 100(68.5%)T 4 stage. Comparatively, there were 19(11.7%)T 1 stage, 68(42.0%)T 2 stage, 40(24.7%)T 3stage, and 35(21.6%)T 4 stage in the other group. There were no statistically significant difference between the two groups in term of age( P=0.057) and TPV( P=0.222). Univariate and multivariate logistic regression analysis showed that tPSA( P=0.003), SII( P<0.001), T clinical stage( P<0.001)could be regarded as independent risk factors of bone metastasis of PCa. Area under the curve of SII+ tPSA was 0.770, which was higher than SII(0.653)or tPSA(0.729) alone( P<0.05). When the cut-off value was 727.72/L, the sensitivity and specificity of the diagnosis of SII alone were 38.4% and 87.7%. The sensitivity and specificity of tPSA alone were 67.1%and 75.9% when the cut-off value was 73.02ng/ml. The sensitivity was 72.6% and the specificity was 71.6% when SII and tPSA was combined. Conclusions:SII is an independent predictor of bone metastasis of newly diagnosed with PCa. , and the patients were at high risk when SII exceeded 727.72/L. The combination of SII and tPSA can improve its predictive validity for the risk of bone metastasis.

BACKGROUND:Our previous studies have shown that the poly(hydroxybutyrate- co-hydroxyvalerate) - sol-gel bioactive glass (PHBV-SGBG) has good biocompatibility and promote bone tissue repair, but its specific role in periodontal tissue regeneration has not been investigated. OBJECTIVE:To investigate the periodontal regenerative effects of a PHBV-SGBG scaffold in beagle dogs. METHODS:Alveolar bone defects (5 mm×5 mm) were surgicaly created bilateraly at the buccal side of the mandibular third and fourth premolars of four beagle dogs. PHBV-SGBG scaffold was randomly filed in the defects as experimental group and nothing was put into the contralateral as control group. Histological and scanning electron microscopy observations, cone-beam CT evaluation and the Ca/P concentration ratio analysis were processed at 2, 4, 8 and 12 weeks after surgery. RESULTS AND CONCLUSION:After surgery, the height of the regenerated tissue increased with time in both groups, and the regenerated tissue height in the experiment group was higher than that in the control group (P < 0.05). At 12 weeks after surgery, the Ca/P concentration ratio of the experiment group was close to that in the normal tissue (P > 0.05), but higher than that of the control group (P < 0.05); the histological observation showed that the regenerated tissue of the experimental group was close to the normal tissue, and the regenerated tissue of the control group tended to be mature, with a smal amount of new blood vessels. Under the scanning electron microscope, no scaffold structure was visible in the experimental group with the presence of bone lacuna at 8 weeks after surgery, while in the control group, there was no bone lacuna and obvious osteoblasts; at 12 weeks after surgery, the structure of the regenerated tissue of experimental group was more regular and close to the normal tissue with no remarkable osteoblasts, and in the control group, the regenerated tissue was disordered, with several cavity. These results show that the PHBV-SGBG scaffold can enhance periodontal bone regeneration effectively.

OBJECTIVE: To discuss the clinical characteristics of bilateral bronchial foreign body in children, increase the curative rate and reduce the complications. METHOD: The clinical data of 35 cases with bilateral bronchial foreign body in children were retrospectively analysed, including surgery, key surgery points, and postoperative combined therapy. RESULT: The foreign bodies of all cases were removed under intravenous general and tropical anesthesia without complications. CONCLUSION The bilateral bronchial foreign body is a serious case, the timely and effective treatment can lower the mortality rate and postoperative complications. The children lack of oxygen for a long time before and in operation should be give comprehensive therapy, for example: sedation and hyperbaric oxygen.
Anesthesia ; Bronchi ; pathology ; Bronchoscopy ; Child ; Foreign Bodies ; diagnosis ; surgery ; Humans ; Oxygen ; Postoperative Period ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To compare the postoperative nutritional status and the incidence of postoperative infection between post-laryngectomy patients with early eternal nutrition and those with normal liquid diet. METHOD: The observational group were given eternal nutrition while the control group were given normal liquid diet. Nutrition indicators (total protein, albumin, globulin, prealbumin, hemoglobin, body weight) and immune parameters (lymphocyte count) were measured at preoperative day 3 and postoperative day 3, 7 and 10. The incidence of complications and postoperative hospitalization days were compared and analyzed. RESULT: Compared with the control group, the total protein, albumin and globulin of observational group had no statistic significance at postoperative day 3, the total protein, albumin,globulin of observational group were higher (P<0. 05) at postoperative day 7 and 10: The body weight had no satisic significance at postoperative day 3 and 7, while observation group higher at postoperative day 10, while the hemoglobin of observational group had no statistic significance: The prealbumin and lymphocyte count had no statistic significance. The postoperative hospitalization days of the observational group was lower (P<0. 05) than the control group. CONCLUSION The early eternal nutrition for post-laryngectomy patients are conducive to improve of nutritional status and reduce the rate of post-operative complications.
Blood Proteins ; chemistry ; Enteral Nutrition ; Humans ; Laryngectomy ; Lymphocyte Count ; Nutritional Status ; Postoperative Complications ; prevention & control ; Postoperative Period

The changes of serum malondialdehyde, myeloperoxidase, total antioxidant capacity, superoxide dismutase activity, and glutathione peroxidase were observed in patients with Graves′ disease. The myeloperoxidase level increased in patients with Graves′ disease. The balance between oxidation and antioxidative defense was disrupted in patients with newly-onset Graves′ disease. Oxidative stress seems to be related to hyperthyroidism.

Objective To investigate the indications and clinical effect of the low-big hole choledochoduodenostomy. Methods Two hundred and ninty-eight patients, had bile duct stone accompanied with common bile duct lower segment stenosis, were prospectively enrolled into the study and randomly divided into the low-big hole choledochoduodenostomy (improved CD ) group (n = 148 ) and the Roux-en-Y choledochojejunostomy (CJ) group (n = 150). Their perioperative period and long term effect indices were recorded and compared. Results Perioperative period indices:The time of cholangio-jejunostomy was much shorter in improved CD group than the CJ group ([31.0±10.5] min vs [53.0±12.3] min, P＜0.001);The anastomotic leakage was significantly less in improved CD group than the CJ group (2 vs 9, P ＜ 0. 001 ). The long term effect indices: The occurrence of peptic ulcer (3 vs 15 ) and the bile duct cecum or blind loop syndrome (5 vs 158) were significantly lower in group improved CD group than CJ group (Ps＜0.01);The occurrence of bile duct backflow (70 vs 42) was significantly higher in improved CD group than CJ group (P＜0. 0l). Conclusion The clinical effect of the low-big hole choledochoduodenostomy gastrointestinal had excellent effect for bile duct stone accompanied with common bile duct lower segment stenosis, especially for old,weak and critical patients,and it can not be replaced by the Roux-en-Y choledochojejunostomy.