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.

OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged

Object·To explore the effects of comorbid obsessive-compulsive personality disorder(OCPD)on the behavioral inhibition system(BIS)/behavioral activation system(BAS)in patients with obsessive-compulsive disorder(OCD).Methods·A total of 247 patients with unmedicated OCD diagnosed in the Mental Health Center,Shanghai Jiao Tong University School of Medicine from 2014 to 2018 were included and divided into an OCD group(n=202),and an OCD+OCPD group(n=45),and 107 healthy controls were recruited as a comparison group.Yale-Brown Obsessive-Compulsion Scale(YBOCS),BIS/BAS Scale,Hamilton Depression Scale(HAMD),and Hamilton Anxiety Scale(HAMA)were used to assess psychopathological features.Gender differences among the three groups were analyzed using the x2 test.One-way analysis of variance(ANOVA)was used to compare differences in demographic characteristics,psychopathological features,and BIS/BAS scores,followed by the least significant difference(LSD)test for pairwise comparisons.Regression analysis was conducted to explore the relationships between psychopathological features and BIS/BAS scores.Results·There were no significant differences in gender,age,and years of education among the three groups.The scores of YBOCS(t=2.925,P=0.004),HAMD(t=2.130,P=0.034)and HAMA(t=2.568,P=0.011)in the OCD+OCPD group were significantly higher than those in the OCD group.There were statistically significant differences in BIS and BAS scores among the three groups(BIS:F=39.573,P＜0.001;BAS:F=3.915,P=0.021).The results showed that for BIS,there were statistically significant differences in pairwise comparisons among the three groups(OCD+OCPD vs OCD:P=0.002;OCD+OCPD vs HC:P＜0.001;OCD vs HC:P＜0.001),and the scores were OCD+OCPD＜OCD＜HC from low to high.For BAS,the OCD group scored significantly higher than the OCD+OCPD and HC groups(OCD+OCPD vs OCD:P=0.018;OCD vs HC:P=0.043),but there was no significant difference between the OCD+OCPD and HC groups.Regression models of BIS and BAS were constructed for OCD patients with OCPD,and the results showed that the overall prediction effect of the model was significant for BIS total scores(F=2.599,P=0.013).Only the severity of OCPD symptoms can significantly predict BIS scores(t=-2.282,P=0.023).For BAS total scores,the overall prediction effect of the model was not significant(F=1.438,P=0.191).Conclusion·Comorbid OCPD may be an adverse factor for abnormal BIS and a protective factor for abnormal BAS in patients with OCD.

Object·To explore the effects of comorbid obsessive-compulsive personality disorder(OCPD)on the behavioral inhibition system(BIS)/behavioral activation system(BAS)in patients with obsessive-compulsive disorder(OCD).Methods·A total of 247 patients with unmedicated OCD diagnosed in the Mental Health Center,Shanghai Jiao Tong University School of Medicine from 2014 to 2018 were included and divided into an OCD group(n=202),and an OCD+OCPD group(n=45),and 107 healthy controls were recruited as a comparison group.Yale-Brown Obsessive-Compulsion Scale(YBOCS),BIS/BAS Scale,Hamilton Depression Scale(HAMD),and Hamilton Anxiety Scale(HAMA)were used to assess psychopathological features.Gender differences among the three groups were analyzed using the x2 test.One-way analysis of variance(ANOVA)was used to compare differences in demographic characteristics,psychopathological features,and BIS/BAS scores,followed by the least significant difference(LSD)test for pairwise comparisons.Regression analysis was conducted to explore the relationships between psychopathological features and BIS/BAS scores.Results·There were no significant differences in gender,age,and years of education among the three groups.The scores of YBOCS(t=2.925,P=0.004),HAMD(t=2.130,P=0.034)and HAMA(t=2.568,P=0.011)in the OCD+OCPD group were significantly higher than those in the OCD group.There were statistically significant differences in BIS and BAS scores among the three groups(BIS:F=39.573,P＜0.001;BAS:F=3.915,P=0.021).The results showed that for BIS,there were statistically significant differences in pairwise comparisons among the three groups(OCD+OCPD vs OCD:P=0.002;OCD+OCPD vs HC:P＜0.001;OCD vs HC:P＜0.001),and the scores were OCD+OCPD＜OCD＜HC from low to high.For BAS,the OCD group scored significantly higher than the OCD+OCPD and HC groups(OCD+OCPD vs OCD:P=0.018;OCD vs HC:P=0.043),but there was no significant difference between the OCD+OCPD and HC groups.Regression models of BIS and BAS were constructed for OCD patients with OCPD,and the results showed that the overall prediction effect of the model was significant for BIS total scores(F=2.599,P=0.013).Only the severity of OCPD symptoms can significantly predict BIS scores(t=-2.282,P=0.023).For BAS total scores,the overall prediction effect of the model was not significant(F=1.438,P=0.191).Conclusion·Comorbid OCPD may be an adverse factor for abnormal BIS and a protective factor for abnormal BAS in patients with OCD.

Objective To explore prenatal ultrasonic characteristics of fetal Currarino syndrome(CS)and methods for prenatal diagnosis of CS.Methods Two fetuses with CS confirmed by genetic examination were retrospectively analyzed,while 6 CS fetuses with complete prenatal ultrasonic data in literature were reviewed.Prenatal ultrasonic characteristics of CS fetuses and the method for prenatal diagnosis of CS were discussed.Results Among 8 CS fetuses diagnosed with prenatal ultrasound,4 were female singletons with a clear family history of CS,and MNX1 gene mutation was found in 1 fetus.The other 4 fetuses were 2 pairs of male monochorionic twins,all with MNX1 gene mutation.Among 8 CS fetuses,complete triad(sacral agenesis abnormalities,anorectal malformation and presacral mass)were displayed only in 2 fetuses,while all 8 had sacral agenesis abnormalities and 6(6/8,75.00％)were detected with prenatal ultrasound,6 had low location of conus medullaris and 2(2/6,33.33％)detected with prenatal ultrasound.Conclusion Prenatal ultrasound was the first choice for non-invasive diagnosis of fetal CS.When one of sacral agenesis abnormalities,anorectal malformation and presacral mass was found with prenatal ultrasound,the possibility of CS should be considered,and fetal MRI,genetic examination and prenatal genetic counselling should be recommended if necessary.

Diagnostics is one of the most important bridge courses for medical students from basic to clinical. Doctor-patient communication runs through the whole process of patient diagnosis and treatment. How to improve medical students' ability of doctor-patient communication? Our teaching team has carried out continuous reform and explored the scientific effective teaching mode. Recently, through the construction of "doctor-patient communication skills" quality online course, efforts have made to build an online and offline blended learning mode, which has gradually realize the integration with diagnostics teaching, and has achieved remarkable results. It also provides a scientific practical basis for the integration of doctor-patient communication and other clinical courses, which is worthy of promotion.

Objective:To explore the therapeutic effect of group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).Methods:This study used a randomized controlled trial design to compare GCBT with routine medication treatment. Unmedicated ninety-four patients who met the inclusion criteria were recruited and randomly allocated to GCBT group ( n=47) and drug treatment group ( n=47) by a simple random grouping method using the RAND function in Excel software which generated a table of random numbers to form a random grouping sequence. Both groups were treated for 12 weeks. The average reduction rate and value of Y-BOCS, HAMA 14 and HAMD 24 were compared between the two groups, t-test,chi-square (χ 2) test and variance analysis (ANOVA) were condulted to analyze data. Results:(1) There was no significant difference between two groups in Y-BOCS and HAMA 14 scores at baseline ( t=0.281, P=0.779; t=0.795, P=0.429), but HAMD 24 scores were significantly different ( t=2.316, P<0.05). Sixteen patients in GCBT group and sixteen in drug treatment group dropped out of treatment, resulted a total drop-out rate of 34%. There was no significant difference in the drop-out rate between the two groups. (2) After 12-week treatment, the Y-BOCS scores decreased compared to pre-treatment in both groups. There was no statistical difference in the mean reduction rate ((37.0±27.4)% vs. (45.5±22.9)%) and score (9.0±6.3 vs.11.0±5.8) of Y-BOCS ( F(1,62)=0.069, P=0.794; F(1,62)=0.001, P=0.975) before and after treatment between the two groups. There was no statistical difference in the effective and cure rate between the two groups (χ 2=1.653, P=0.199; χ 2=0.088, P=0.767) . (3) There was no significant difference in the mean reduction rate and score of HAMA 14 ( t=-0.922, P=0.362; t=1.082, P=0.286). (4) No significant difference was found regarding the mean reduction rate of HAMD 24 between the two groups, but the mean reduction scores of HAMD 24 in the medication group were significantly higher than those in GCBT group ( t=2.239, P=0.029). Conclusion:GCBT is equivalent to conventional medication treatment for obsessive-compulsive and anxiety symptoms for OCD patients, and medication treatment is superior to GCBT in depressive symptoms.

Objective:To explore the therapeutic effect of group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).Methods:This study used a randomized controlled trial design to compare GCBT with routine medication treatment. Unmedicated ninety-four patients who met the inclusion criteria were recruited and randomly allocated to GCBT group ( n=47) and drug treatment group ( n=47) by a simple random grouping method using the RAND function in Excel software which generated a table of random numbers to form a random grouping sequence. Both groups were treated for 12 weeks. The average reduction rate and value of Y-BOCS, HAMA 14 and HAMD 24 were compared between the two groups, t-test,chi-square (χ 2) test and variance analysis (ANOVA) were condulted to analyze data. Results:(1) There was no significant difference between two groups in Y-BOCS and HAMA 14 scores at baseline ( t=0.281, P=0.779; t=0.795, P=0.429), but HAMD 24 scores were significantly different ( t=2.316, P<0.05). Sixteen patients in GCBT group and sixteen in drug treatment group dropped out of treatment, resulted a total drop-out rate of 34%. There was no significant difference in the drop-out rate between the two groups. (2) After 12-week treatment, the Y-BOCS scores decreased compared to pre-treatment in both groups. There was no statistical difference in the mean reduction rate ((37.0±27.4)% vs. (45.5±22.9)%) and score (9.0±6.3 vs.11.0±5.8) of Y-BOCS ( F(1,62)=0.069, P=0.794; F(1,62)=0.001, P=0.975) before and after treatment between the two groups. There was no statistical difference in the effective and cure rate between the two groups (χ 2=1.653, P=0.199; χ 2=0.088, P=0.767) . (3) There was no significant difference in the mean reduction rate and score of HAMA 14 ( t=-0.922, P=0.362; t=1.082, P=0.286). (4) No significant difference was found regarding the mean reduction rate of HAMD 24 between the two groups, but the mean reduction scores of HAMD 24 in the medication group were significantly higher than those in GCBT group ( t=2.239, P=0.029). Conclusion:GCBT is equivalent to conventional medication treatment for obsessive-compulsive and anxiety symptoms for OCD patients, and medication treatment is superior to GCBT in depressive symptoms.

Objective To evaluate the effect of hydrogen on mitochondrial fusion during myocardial ischemia-reperfusion (I/R) in aged rats.Methods One hundred and fifty pathogen-free healthy male Sprague-Dawley rats,aged 18 months old,weighing 400-500 g,were divided into 5 groups (n=30 each) using a random number table:control group (group C),sham operation group (group S),group I/R,normal saline group (group NS) and hydrogen-rich saline group (group H).Group C received no treatment.The anterior descending branch was only exposed but not ligated in group S.Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 rmin followed by reperfusion in I/R,NS and H groups.Hydrogen-rich saline 1 ml/100 g was injected intraperitoneally at 5 min before reperfusion in group H,while normal saline 1 ml/100 g was injected intraperitoneally at 5 min before reperfusion in group NS.The rats were sacrificed at 12 and 24 h of reperfusion,and hearts were removed for examination of the pathological changes and for determination of apoptosis in cardiomyocytes (by TUNEL) and expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues (by Western blot or real-time polymerase chain reaction).The apoptosis index was calculated.Results Compared with C and S groups,the apoptosis index of cardiomyocytes was significantly increased and the expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues was down-regulated at 12 and 24 h of reperfusion in I/R,NS and H groups (P＜0.05).Compared with NS and I/R groups,the apoptosis index of cardiomyocytes was significantly decreased and the expression of Mfn1 and Mfn2 protein and mRNA in myocardial tissues was up-regulated at 12 and 24 h of reperfusion in group H (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group H when compared with group I/R.Conclusion The mechanism by which hydrogen attenuates myocardial I/R injury is related to promoting mitochondrial fusion and inhibiting apoptosis in cardiomyocytes of aged rats.

Objective To explore the association between impulsively aggressive behavior and rs6922753 single nucleotide polymorphism of glutamate receptor 6 (GluR6) gene in Xinjiang Uygur and Han patients with bipolar disorder.Methods The techniques of polymerase chain reaction (PCR) and DNA sequencing technique were conducted to detect rs6922753 single nucleotide polymorphism of GluR6 gene in 240 patients with bipolar disorder.The association between the polymorphisms and impulsively aggressive behavior was analyzed with SPSS 17.0 software.Results No statistical difference was observed between the impulsively aggressive behavior group and the no impulsively aggressive behavior group of Xinjiang Han and Uygur patients with bipolar disorder in the genotype and allele frequencies for the investigated rs6922753 polymorphisms (P ＞ 0.05).Conclusions No association was found between the impulsively aggressive behavior and rs6922753 single nucleotide polymorphism of GluR6 gene in Xinjiang Uygur and Han patients with bipolar disorder.