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 discuss the effect of temperature-controlled shrinkage polytrimethylene carbonate(PTMC)/polyvinylpyrrolidone(PVP)nanofiber membrane on the biological behavior of mouse fibroblasts and the repairment effect on full-thickness skin defects in the rats,and to clarify the potential mechanism.Methods:The murine L929 fibroblast cells were used in the in vitro experiments and were divided into control group and experimental group(treated with PTMC/PVP nanofiber membranes).The proliferation activities of the cells in two groups were detected by CCK-8 assay;the numbers of live/dead cells in two groups were observed by live/dead cell staining;the morphology of the cells was observed by cytoskeletal staining.A total of 12 six-week-old male SD rats were selected in the in vivo experiment,and were randomly divided into control group and experimental group,and there were six rats in each group.The full-thickness skin defect model was established,and the rats in experimental group were treated with PTMC/PVP nanofiber membranes.The photographs were taken after operation,and the wound healing rates of the cells in two groups were calculated on the 0,3rd,6th,and 12th days.On the 6th and 12th days after operation,the skin samples around the wound of the rats in two groups were taken,and the histopathology of the would skin and adjacent tissue was detected by HE staining;the collagen deposition in wound skin tissue of the rats in two groups was observed by Masson trichrome staining;the numbers of angiogenesis in wound skin tissue of the rats were detected by CD31 immunohistochemical staining.Results:The CCK-8 assay results showed that the proliferation activity of the cells in experimental group showed an increasing trend on the 1st,3st,and 5st days,and there was no significant difference in the proliferation activities of the cells bewteen experimental group and control group(P＞0.05).The live/dead cell staining experiment results showed that compared with control group,the cell density and number of the cells in experimental group had no significant changes,and were predominantly live cells.The cytoskeletal staining results showed that the cells in experimental and control groups appeared spindle-shaped and well-spread.In the in vivo experiments,on the 3rd,6th,and 12th days,compared with control group,the wound healing rates of the cells in experimental group were increased(P＜0.01),and the wound healing rate of the cells was 95.45％on the 12th day,indicating nearly complete healing of the wound.The HE staining showed that on the 12th day,the wound skin structure of the cells in experimental group was more similar to the normal skin,and there was abundant granulation tissue,regular epidermal structure,and new blood vessel formation.The Masson trichrome staining results showed that compared with control group,the collagen deposition in wound tissue of the rats in experimental group was increased.The immunohistochemical staining results showed that the expression of CD31 in wound tissue of the rats in experimental group was increased,indicating the increasing of the number of angiogenesis.Conclusion:The PTMC/PVP thermoresponsive nanofiber membranes exhibit good biocompatibility and can promote the repairment of full-thickness skin defects in the rats;its mechanism may be related to the enhancement of proliferation activity of the basal cells.

ObjectiveIn order to explore the utilization value of the seeds dropped in the harvesting， processing， storage and transportation of Prunellae Spica， the character， turgidity and chemical composition of the seeds were analyzed and compared with those of the commercially available varieties， such as chia seeds and basil seeds. MethodCharacter was observed directly. The turgidity was determined according to the method of general rule 2101 of Chinese Pharmacopoeia （part Ⅳ， the 2020 edition）. The contents of six phenolic acids （danshensu， protocatechuic acid， protocatechuic aldehyde， caffeic acid， salviaflaside and rosmarinic acid） were determined by ultra performance liquid chromatography （UPLC）， acetonitrile （A）-0.1% formic acid aqueous solution （B） was used as mobile phase for gradient elution （0-7 min， 2%-8%A； 7-13 min， 8%A； 13-14 min， 8%-17%A； 14-30 min， 17%A）， the detection wavelength was at 280 nm. The liposoluble components were extracted by n-hexane and identified by gas chromatography-mass spectrometry （GC-MS）， and the contents of five fatty acids， namely palmitic acid， oleic acid， stearic acid， linolic acid and α-linolenic acid， were determined on a DB-35MS capillary column （0.25 mm×60.0 m， 0.25 µm）， the injection temperature was 250 ℃， the carrier gas was high-purity helium with a flow rate of 1.0 mL·min^-1 and the splitting ratio of 50∶1. The volatile oil was extracted by steam distillation method and its components were identified by GC-MS on a WM-5MS capillary column （0.25 mm×30.0 m， 0.25 µm） with the injection temperature of 250 ℃， the flow rate of 1.0 mL·min^-1 and the splitting ratio of 10∶1. ResultPrunellae Spica seeds were slightly smaller than chia seeds and basil seeds， and their color of seed coat was obviously different. Prunellae Spica seeds had strong water absorption and swelling characteristics， and the turgidity was 17.4 mL·g^-1， which was lower than that of chia seeds （25.2 mL·g^-1） and basil seeds （35.6 mL·g^-1）. Prunellae Spica seeds were rich in phenolic and fatty acids， while the content of volatile oil was very low. The main phenolic acids were salviaflaside and rosmarinic acid， with the contents of 0.579% and 0.392%， respectively. The total content of five fatty acids in n-hexane extract was 90.1%， and total content of unsaturated fatty acids was 80.6%， among which content of α-linolenic acid was 50.0%， which was slightly lower than 57.2% of chia seeds and similar to 50.0% of basil seeds. ConclusionPrunellae Spica seeds have good turgidity， rich in phenolic acids and unsaturated fatty acids， and especially with high amount of α-linolenic acid. It is worthy of being developed as functional food to realize comprehensive utilization of the waste resources of Prunellae Spica.

Indocyanine Green/therapeutic use* ; Photochemotherapy ; Combined Modality Therapy ; Anti-Infective Agents

Objective:To explore the cause and treatment of chylothorax after surgery for congenital heart disease(CHD) in newborns.Methods:A retrospective analysis was made to the clinical data of 49 newborns with chylothorax after surgery for CHD within the period from January 2009 to December 2019. These newborns were aged from from 1 day to 28 days with the weight from 2.0 kg to 4.1 kg. The complete transposition of great arteries was performed in 13 cases, coarctation of the aorta/ interruption of the aortic arch in 13 case, right ventricular outflow tract reconstruction/ Blalock-Taussing shunt in 9 cases, total anomalous pulmonary venous connection in 8 cases, ventricular septal defect repair and atrial septal defect repair in 4 cases, ligation of patent ductus arteriosus in 1 case and persisten truncus arteriosus in 1 case. Chylothorax occurred in the right in 19 cases, left side in 20 cases, bilateral in 9 cases and the pericardium in 1 case. The diagnosis was made at the time from 1 day to 22 days after the surgery with an average of 8 days.Results:43 patients were cured(87.75%), 41 cases(83.67%) were cured with diet and support therapy, the course lasted from 4 days to 65 days with an average of 11 days; 1 cases, because of the poor effect of diet and support therapy, was given pleural injection of high-sugar combined with octreotide treatment; 1 case received thoracic duct ligation as the conservative therapy was ineffective; 6 cases of death due to heart failure/ severe pulmonary hypertension after operation, and parents gave up.Conclusion:Individualization conservative therapy is the first choice for chylothorax, while timely surgery can raise the survival rate and save the hospitalization time and the cost.

Primary liver cancer (liver cancer) is one of the main indications of liver transplantation in China. Nevertheless, the 5-year survival rate of liver transplant recipients is lower than 50%. Recurrence and metastasis after operation are the main causes affecting the long-term survival of the recipients. At present, immunotherapy, represented by programmed cell death protein 1(PD-1)/programmed cell death protein-ligand 1(PD-L1) immune checkpoint inhibitor, has achieved remarkable clinical efficacy in the treatment of middle-stage and advanced liver cancer. However, whether it can be applied in recipients with recurrence and metastasis after liver transplantation for liver cancer remains controversial. The main reason is that it may cause acute rejection at the same time. In this article, the research progresses on the application of immunotherapy in recipients with recurrence and metastasis after liver transplantation for liver cancer were reviewed, aiming to improve the survival rate of recipients undergoing liver transplantation forliver cancer.

Organ transplantation is one of the effective methods for the treatment of end-stage diseases, but the lack of donors has hindered the development of organ transplantation. Extracorporeal membrane oxygenation (ECMO) can improve the hypoxia and hypoperfusion of organs, shorten the warm ischemia time, and maintain the function of donor organs effectively, in case of emergency or donor hemodynamic instability. It helps to make effective use of donor organs and benefit patients who are in urgent need of organ transplants. This article summarized the progress on application of ECMO in donor maintenance and provided suggestions for its application in organ transplantation.

Objective:To investigate the safety of inter-hospital referral and the prognosis of neonatal with critical congenital heart disease.Methods:The criticality score, transit distance and time, and the prognosis of 237 newborns with critical congenital heart disease in Guangdong Provincial People′s Hospital from July 2016 to July 2018 were retrospectively analyzed.Results:A total of 237 children were included (162 male and 75 female) with the median age of 6 days and the median body weight of 2.98 kg.The median transit distance was 90 km.The average value of neonatal critical illness score (NCIS) was (86.54±9.05) scores before transport; 136 cases were greater than 90 scores, 84 cases between 70 and 90 scores, 17 cases less than 70 scores; while the average NCIS was (87.05±8.19) scores when arrived at neonatal intensive care unit (NICU), 138 cases were greater than 90 scores, 82 cases between 70 and 90 scores, 17 cases less than 70 scores.There were no significant differences in the scores of critical cases before and after transfer according to the transfer time and distance ( t=0.346, P>0.05). There was no one death occurred during the transfer process.All over, 222 cases were cured and discharged from the hospital after surgery and or medical interventional treatments, 15 cases died after giving up treatment or losing the opportunity for surgery. Conclusions:It is safe and effective of the inter-hospital transport for the rescue of infants with critical congenital heart disease when followed the principles and transport rules and regulations, with trained workers and special equipments.

Objective: To discuss the effect of self-efficacy on patients with coronary heart disease cured in general practice department based on Hospital-Community-Patient Integrated Nursing Mode. Methods: From January to April in 2018, 106 patients (51 males and 55 females) with coronary heart disease hospitalized in general practice of hospital were selected as subjects of study. Random number table method was used to divide the patients into control group and intervention group, 53 cases in each group. The intervention group adopted the hospital-community-patient integrated nursing model, while the control group adopted the traditional health education mode after discharge. Self-efficacy evaluation was conducted before intervention, 3 months after intervention and 6 months after intervention. Results: The total score of self-efficacy in the two groups was higher than that before intervention, but the increase in the intervention group was significantly better than that in the control group, the difference was statistically significant (F=34.681, P < 0.01). The total scores of self-efficacy in intervention group were(30.35±2.58), (33.59±2.68) points respectively 3 months and 6 months after intervention, which were higher than (28.95±2.42), (29.10±2.12) points in control group. The difference was significant (t = 3.702, 13.494, P < 0.01). Conclusion Hospital-community-patient integrated nursing model is superior to traditional health education model after discharge, which can significantly improve the self-efficacy of patients with coronary heart disease discharged from general practice department.

Objective: To analyze the neurodevelopmental outcome and its risk factors in infants with CHD at 18 months of age. Methods: Eighteen-month-old infants with CHD at the follow-up clinic of our hospital were selected. The Bayley scales of infant development(BSID) were used to evaluate the levels of mental development(MDI) and psychomotor development(PDI). The clinical features during hospitalization were reviewed, and the risk factors of MDI and PDI were analyzed. Results: A total of 116 children with CHD underwent BSID evaluation at 18 months of age. Both the MDI(95.38±22.98) and PDI(87.84±22.57) of the cohort were significantly lower than the average value of the normal population(P<0.05). In infants with cyanotic CHD, the MDI was higher(β=17.218). The longer the length was of the hospital stay, the lower the PDI(β=-0.577). In patients undergoing cardiopulmonary bypass surgery, the PDI was higher(β=11.956). Compared to infants with relatively normal behavior, the PDI of infants with mild behavioral problems was lower(β=-10.605). Conclusion Children with CHD who underwent cardiac surgery have delayed neurodevelopmental outcomes compared with those of healthy children. The outcomes of infants with cyanotic CHD or undergoing cardiopulmonary bypass surgery was better than others. Long hospital stays and mild behavioral problems were risk factors for poor neurodevelopmental outcomes.