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 evaluate the relationship between postoperative delirium (POD) and concentrations of phosphatidylethanolamine-binding protein 1 (PEBP1) in cerebrospinal fluid (CSF) of elderly patients undergoing total knee and hip arthroplasty.Methods:In this case-control study, 375 elderly patients of both sexes, aged ≥65 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective total knee and hip arthroplasty under combined spinal-epidural anesthesia at Haian Hospital Affiliated to Nantong University from November 2022 to June 2024, were selected. The perioperative clinical data were collected. CSF was drawn before anaesthesia for determination of the concentrations of PEBP1, Abeta 42 (Aβ 42), total tau (t-tau) and phosphorylated tau (p-tau) by enzyme-linked immunosorbent assay. The occurrence of postoperative delirium was evaluated using the Confusion Assessment Method at 1-7 days after operation. The severity of POD was assessed using a Memorial Delirium Assessment Scale. The patients were divided into POD group and non-POD group based on whether POD occurred. The influencing factors of POD were analyzed using multivariate logistic regression. Mediating effects were assessed to determine whether the levels of Aβ 42, p-tau and t-tau in CSF mediated PEBP1′s effect on POD. The accuracy of CSF PEBP1 concentration in predicting POD was evaluated using the receiver operating characteristic curve. Results:Decreased concentration of Aβ 42 in CSF, decreased ratios of Aβ 42/p-tau and Aβ 42/t-tau in CSF, and increased concentrations of PEBP1, p-tau and t-tau in CSF were independent risk factors for POD ( P<0.05). The results of mediation analysis showed that the relationship between PEBP1 and POD was partially mediated by CSF Aβ 42 (15.0%) and Aβ 42/t-tau ratio (14.9%). The receiver operating characteristic curve showed that the accuracy of CSF PEBP1 concentrations in predicting the occurrence of POD was high (AUC=0.846, P<0.001). Conclusions:Preoperative elevated CSF PEBP1 concentration is a risk factor for POD. CSF Aβ 42 concentration and Aβ 42/t-tau ratio serve as key mediators in the the association between PEBP1 and POD. PEBP1 concentration is more accurate in predicting POD.

Objective:To evaluate the relationship between postoperative delirium (POD) and concentrations of phosphatidylethanolamine-binding protein 1 (PEBP1) in cerebrospinal fluid (CSF) of elderly patients undergoing total knee and hip arthroplasty.Methods:In this case-control study, 375 elderly patients of both sexes, aged ≥65 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective total knee and hip arthroplasty under combined spinal-epidural anesthesia at Haian Hospital Affiliated to Nantong University from November 2022 to June 2024, were selected. The perioperative clinical data were collected. CSF was drawn before anaesthesia for determination of the concentrations of PEBP1, Abeta 42 (Aβ 42), total tau (t-tau) and phosphorylated tau (p-tau) by enzyme-linked immunosorbent assay. The occurrence of postoperative delirium was evaluated using the Confusion Assessment Method at 1-7 days after operation. The severity of POD was assessed using a Memorial Delirium Assessment Scale. The patients were divided into POD group and non-POD group based on whether POD occurred. The influencing factors of POD were analyzed using multivariate logistic regression. Mediating effects were assessed to determine whether the levels of Aβ 42, p-tau and t-tau in CSF mediated PEBP1′s effect on POD. The accuracy of CSF PEBP1 concentration in predicting POD was evaluated using the receiver operating characteristic curve. Results:Decreased concentration of Aβ 42 in CSF, decreased ratios of Aβ 42/p-tau and Aβ 42/t-tau in CSF, and increased concentrations of PEBP1, p-tau and t-tau in CSF were independent risk factors for POD ( P<0.05). The results of mediation analysis showed that the relationship between PEBP1 and POD was partially mediated by CSF Aβ 42 (15.0%) and Aβ 42/t-tau ratio (14.9%). The receiver operating characteristic curve showed that the accuracy of CSF PEBP1 concentrations in predicting the occurrence of POD was high (AUC=0.846, P<0.001). Conclusions:Preoperative elevated CSF PEBP1 concentration is a risk factor for POD. CSF Aβ 42 concentration and Aβ 42/t-tau ratio serve as key mediators in the the association between PEBP1 and POD. PEBP1 concentration is more accurate in predicting POD.

In public health emergencies,medical emergency response efforts face governance challenges such as complex and variable tasks,difficulties in team organization,and uncertain working areas.The establishment of temporary party organiza-tions plays a crucial role in efficiently achieving the goals of medical emergency teams and stabilizing social order.This paper an-alyzes the functional positioning,key tasks,and operational mechanisms of temporary party organizations within Guangdong's medical teams aiding in the pandemic response.The study finds that these temporary party organizations effectively address the complex challenges of public health emergencies through functions such as strengthening political leadership,mobilizing public support,coordinating organization,and serving the community.This provides important insights for advancing the construction of governance systems for public health emergencies in China.

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.

Objective:To evaluate the effect of goal-directed fluid therapy (GDFT) based on stroke volume variation (SVV) guidance on splanchnic perfusion using gastric mucosal pH (pHi) value in elderly patients undergoing lumbar spine surgery.Methods:One hundred and sixty elderly patients of either sex, aged 65-80 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective lumbar spine surgery under general anesthesia, were selected and divided into 2 groups ( n=80 each) using a random number table method: SVV-guided GDFT group (group G) and conventional fluid therapy group (group C). GDFT was performed with SVV<15% as the target in group G, while conventional fluid infusion was performed under the guidance of mean arterial pressure, central venous pressure and urine volume in group C. Intraoperative amount of crystalloid solution infused, amount of colloid solution infused, total volume of fluid infused, amount of bleeding, urine volume, use of vasoactive drugs and perioperative blood transfusion were recorded in both groups.Cardiac index, SVV, pHi, gastric intramucosal partial pressure of CO 2 (PgCO 2), PaCO 2 and results of arterial blood gas analysis were also recorded before induction of anesthesia (T 1), at 1 h after the start of surgery (T 2) and at the end of surgery (T 3). The postoperative complications, time to first flatus, time to defecation and duration of hospital stay were also recorded in both groups. Results:Compared with group C, the amount of intraoperative crystalloid solution infused, total volume of fluid infused, urine volume and requirement for vasoactive drugs were significantly decreased, the amount of colloid solution infused was increased, cardiac index and pHi value were increased at T 2, 3, and SVV, Pg-aCO 2 and arterial blood lactic acid concentrations were decreased ( P<0.05), and no significant changes were found in the intraoperative amount of bleeding, arterial blood pH value, PaCO 2 and base excess, incidence of postoperative complications, time to first flatus, time to defecation and duration of hospital stay in group G ( P>0.05). Conclusions:GDFT based on SVV guidance is superior to traditional fluid therapy in improving splanchnic perfusion in elderly patients undergoing lumbar spine surgery.

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 investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016.Methods Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation.Results A total of 1183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1124 patients were enrolled. The proportion of men was 36.48% (410/1124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: MoranI = 0.427,Z = 2.646,P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the high-high concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing.Conclusion The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.