Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Liver cancer (LC) remains one of the most prevalent tumors globally. Despite considerable advancements in its clinical treatment in recent years, the global burden of this disease is projected to increase. According to World Health Organization statistics, the number of LC deaths worldwide in 2022 was 760,000, ranking third among all cancers. Therefore, there is an urgent need to delve deeper into the realms of LC diagnosis, prognosis, and treatment. Proteomics, as an emerging technology leveraging mass spectrometry (MS)-based protein identification, liquid chromatography separation, and bioinformatics-driven data integration, enables the systematic characterization of proteome dynamics to address critical challenges in LC research. These challenges include the discovery of diagnostic and prognostic biomarkers as well as therapeutic targets. By scrutinizing the expression of specific proteins in both normal and cancerous tissues through high-throughput protein microarrays, researchers can uncover novel biomarkers. The use of these biomarkers alone or in combination with established ones holds the potential to significantly advance the fields of LC diagnosis, prognosis, and treatment. In general, the application of proteomics has significantly promoted the development of LC research. In this review, we summarized the latest advancements in the application of proteomics in LC, with a particular focus on diagnosis, prognosis, and treatment. We also concluded selected protein markers, aiming to offer guidance for further applications and present additional therapeutic targets for LC.

Radiopharmaceuticals play an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases， malignant tumors， central nervous system diseases， and other diseases. Under the urgent need for clinical diagnosis and treatment as well as medical development， the clinical research of radiopharmaceuticals has become a hotspot in international research. By analyzing the current situation of clinical research on radiopharmaceuticals in Europe， America， and China， the ethical issues of clinical research on radiopharmaceuticals were elaborated from four aspects， including lack of relevant laws and regulations， a higher risk of radiopharmaceuticals， dilemmas in ethical review， and insufficient radiation protection. Response principles and measures were proposed from four aspects， including improving regulations and policies， enhancing radiological protection for all parties involved in the research， strengthening ethical review， and reinforcing the training of relevant personnel， to enhance the quality and level of clinical research on radiopharmaceuticals.

Objective Mendelian randomization(MR)combined with Meta-analysis(MR-Meta analysis)and bioinformatics mining were used to identify the causal relationship between microRNA(miRNA)and ulcerative colitis(UC).The potential biological functions and pathways were analyzed to search for new biomarkers and potential therapeutic targets.Methods MiRNA exposure data and multiple UC outcome data sets were used to identify the causal relationship between miRNA and UC by MR-meta analysis.Then,the mi-croarray data of UC was extracted by gene expression database for differential analysis,the differential expression of MR-Meta-miRNAs was detected,and the differential target genes of the detected candidate miRNA were screened by machine learning algorithm for key genes.Then,the function and pathway of key genes were analyzed by immune cell infiltration and single gene enrichment analysis(GSEA),and the ceRNA regulatory network was constructed.Results Nine miRNA were identified by MR-Meta analysis and were significantly associated with UC risk.The GES48959 chip data analysis showed that the hsa-miR-196b-5p was significantly low-ex-pressed in UC tissues,the differential genes targeted by hsa-miR-196b-5p were then used to obtain the key gene MAP3K1 by two ma-chine learning algorithms.GSEA and immune-infiltration analysis showed that MAP3K1 was a key gene in regulating immune inflamma-tion.The ceRNA regulatory network indicates that lncRNA/hsa-miR-196b-5p/MAP3K1had the potential to regulate UC lesions.Conclusion There is a causal relationship between miRNA and UC,among which hsa-miR-196b-5p is closely related to the risk of UC.The hsa-miR-196b-5p/MAP3KI pathway may affect the occurrence and progression of diseases as a molecular mechanism regu-lating UC immune inflammation,and provide a new idea for exploring the effective diagnosis and treatment of UC in the future.

Objective Mendelian randomization(MR)combined with Meta-analysis(MR-Meta analysis)and bioinformatics mining were used to identify the causal relationship between microRNA(miRNA)and ulcerative colitis(UC).The potential biological functions and pathways were analyzed to search for new biomarkers and potential therapeutic targets.Methods MiRNA exposure data and multiple UC outcome data sets were used to identify the causal relationship between miRNA and UC by MR-meta analysis.Then,the mi-croarray data of UC was extracted by gene expression database for differential analysis,the differential expression of MR-Meta-miRNAs was detected,and the differential target genes of the detected candidate miRNA were screened by machine learning algorithm for key genes.Then,the function and pathway of key genes were analyzed by immune cell infiltration and single gene enrichment analysis(GSEA),and the ceRNA regulatory network was constructed.Results Nine miRNA were identified by MR-Meta analysis and were significantly associated with UC risk.The GES48959 chip data analysis showed that the hsa-miR-196b-5p was significantly low-ex-pressed in UC tissues,the differential genes targeted by hsa-miR-196b-5p were then used to obtain the key gene MAP3K1 by two ma-chine learning algorithms.GSEA and immune-infiltration analysis showed that MAP3K1 was a key gene in regulating immune inflamma-tion.The ceRNA regulatory network indicates that lncRNA/hsa-miR-196b-5p/MAP3K1had the potential to regulate UC lesions.Conclusion There is a causal relationship between miRNA and UC,among which hsa-miR-196b-5p is closely related to the risk of UC.The hsa-miR-196b-5p/MAP3KI pathway may affect the occurrence and progression of diseases as a molecular mechanism regu-lating UC immune inflammation,and provide a new idea for exploring the effective diagnosis and treatment of UC in the future.

Objective:To investigate the proper choice and improve the survival rate in neonates suffering from giant omphalocele (GO)with liver protrusion by analyzing the clinical characteristics, different treatments and outcomes.Methods:Neonates with GO admitted in Department of Neonatal Surgery in Wuhan Children′s Hospital were retrospected from January 2009 to May 2019.The treatment methods include: (1) repaired with similar silo-bag by staged operation; (2) one-stage repair with patch or not; (3) delayed repair by conservative treatment for some time (from 2 to 8 weeks) firstly.Data included gestational age, gender, birth weight, average diameter of omphalocele, contents of omphalocele, associated malformation, treatment method, duration of ventilator use and clinical outcome.These neonates were divided into 2 groups according to the contents of protrusion: group with liver protrusion and group with liver and other organs protrusion.Clinical data were summarized and compared between different groups.Results:Sixteen cases were collected, including 9 males and 7 females.The average age was (1.25±0.45) d (1-2 days), the average birth weight was (2.48±0.37) kg, and pregnant week was (36.23±1.17) weeks.The average diameter of the omphalocele was (9.88±3.30) cm, ranging from 5 cm to 15 cm.Seven cases were belonged to the group with liver protrusion, cases undergone one-stage repair, delayed repair were 6 cases and 1 case, respectively.There were 9 cases in group with liver and other organs protrusion, and the protruded organs included liver, intestine, colon or spleen.Among them, cases needed one-stage repair, delayed repair and silo-bag repair were 3 cases, 3 cases, 3 cases, respectively.Cases needed respiratory machine were 3 cases (42.8%) and 8 cases (88.89%) in group with liver protrusion and group with liver and other organs protrusion, respectively.Neonates had a longer time of needing respiratory machine in group with liver protrusion, comparing with the neonates in group with liver and other organs protrusion[(30.67±19.0) h vs.(106.25±69.36) h, P=0.021], and the risk rate to use respiratory machine was 5.143(95% CI: 0.727-36.368). There were no dead cases in group with liver protrusion.Three cases were dead in group with liver and other organs protrusion.All the patients were followed from 3 months to 4 years, and hernia in abdominal wall was found in 5 cases, including 1 case in group with liver protrusion and 4 cases in group with liver and other organs protrusion.If the dead cases had been excluded, the rate of hernia was 66.7% (4/6 cases) in group with liver and other organs protrusion. Conclusions:Individual treatment should be emphasized in neonates suffering from GO with liver protrusion.Neonates with single liver protrusion have a better prognosis than those with liver and other organs protrusion.One-stage repair is recommended in the former, and the delayed repair is highly recommended in the latter.The accessory liver should be considered when GO neonates presenting liver protrusion.

Objective: To evaluate the indications and outcomes of thoracoscopic repair with hernia-ring pin (TRHP) applied in neonates with congenital diaphragmatic hernia (CDH). Methods: Fifty-six cases diagnosed as CDH were collected from Department of Neonatal Surgery or Cardiothoracic Surgery in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2013 to September 2018.Patients were divided into thoracoscopic repair (TR) group and TRHP group, and the data, including birth weight, pregnant weeks, ages at operation, hospital stay postoperatively and the number of recurrence cases were compared, between the 2 groups.The size of defect was coded into A, B, C and D grades.Status of patients was grouped into Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴstages according to the defect size and complicated congenital heart disease. Results: There were 7 cases in TRHP group, including 3 boys and 4 girls.Four cases belonged to A-class defect and 3 cases were of B-class defect, respectively.The contents of the hernia included small intestine, colon, kidney and spleen.Six cases presented left CDH and 1 case presented right CDH.One of the left CDH cases and the 1 right CDH case had hernia sac.The right CDH neonate presented haematuria in the first day and the second day postoperatively, whose symptom disappeared after treatment.The follow-up time was (12.17±3.41) months, and no recurrent cases were found.All the cases in TRHP group belonged to Ⅰ or Ⅱ stage.There were 49 cases in the TR group.Among them, 29 cases belonged to class-A defect, 18 cases class-B defect, and 4 cases class-C defect, respectively.Cases classified into A and B defects were in stageⅠorⅡ, and cases classified into C defect were in stage Ⅲ.In those 45 cases belonged to A or B defect, 40 cases presented left CDH and 5 case presented right CDH.Among them, 5 neonates had hernia sac.The contents of the hernia included small intestine, colon, kidney and spleen.There were significant differences in the operative time [(83.47±10.28) min vs.(54.29±17.09) min, P<0.05] and length of stay postoperatively [(12.76±5.89) d vs.(7.86±2.03) d, P<0.05] in both groups.TRHP was carried out by the same surgeon, and he also operated on other 18 cases in TR group.Compared with the operative time of cases operated by the same surgeon in both groups, significant diffe-rence was found [(83.47±10.28) min vs.(54.29±17.09) min, P<0.05]. The cases were followed up for (46.17±6.92) months postoperatively and 4 recurrent cases were tracked.One A defect and 1 B defect patients had recurrence 1 month or 2 months postoperatively.Two C defect cases were found to have recurrence postoperatively in 2 months or 6 months, respectively.All 4 cases mentioned above recovered by reoperation.The risk of recurrence in C defect CDH cases existed as high as 21.5 times compared with the A or B defect cases. Conclusions It is safe to repair CDH by THRP in neonates with CDH A or B defect, for their operative time may be shorter.TRHP should be highly recommend for CDH cases with A or B defect.

Objective: To improve the accuracy of the diagnosis and decrease the unnecessary surgical exploration in neonates with simple meconium ileus (SMI) by analyzing clinical characteristics of SMI. Methods: Forty-five neonates identified as SMI from January 2008 to May 2018 had been collected, and the data of pregnancy, birth weight, treatments, hospital stay and results of follow-up were included.The patients were divided into 2 groups: surgical group and non-surgical group.The surgical group underwent enterostomy at the end of ileum, meanwhile, the intestinal wall was biopsied for checking the existence of ganglion cells.All the neonates in the surgical group underwent stoma closure in 3 to 6 months postoperatively.The non-surgical group received fasting, intravenous nutritional support, enema with amiotol diluted into 11 or injected into the stomach by the gastric tube.They all received enema with warm salt (9 g/L) 1-2 times per day.Once the abdominal dilation was mitigated and autonomous defecation obtained, the neonates gradually began the oral feeding and weaned from the total parenteral nutrition(TPN). The 45 neonates were also divided into earlier group (from January 2008 to May 2013) and later group (from June 2013 to May 2018) according to the time of diagnosis.The relationships between the SMI treatment choice and the pregnancy, birth weight and time of diagnosis were analyzed. Results: No cystic fibrosis lesions were found in 45 neonates, of which 21 and 24 neonates were in non-surgical group and surgical group, respectively.In the operation, the intestine presented similar anatomy to the total Hirschsprung′s disease.However, the ganglion was observed not only in the stricture, transitional and dilated zone of ileum, but also in the colon.There were no significant differences in the pregnancy and birth weight in both groups(P>0.05), but there was significant difference in the duration of hospitalization [(21.19±5.13) d vs.(12.29±3.85) d, P=0.000]. There were complications in those patients who had undergone enterostomy, including wound infection (2 cases), prolapse of stoma (2 cases), water and electrolyte disorders (2 cases), malnutrition (21 cases). After the stoma closure, no signs of ganglion cell dysplasia were found in follow-up.In non-surgical group, there were 20 pre-term reonates and 1 full-term neonate, respectively.In surgical group, there were 22 pre-term reonates and 2 full-term neonate, respectively.Neither pregnancy nor birth weight was related to the choice of treatment (P>0.05), but the time when to be admitted was highly related to the choice of treatment (P<0.05). Conclusions It is not rare for the occurrence of SMI in neonates in China, especially in preterm neonates.Amiotol may have effects not only on diagnosis but also on treatment of SMI, which can be applied repeatedly.Non-surgical treatment can help most of the neonates with SMI to avoid surgical exploration.Enhancing apprehension about the SMI may have great advantages to decrease the rate of unnecessary laparotomy.

Objective To investigate the characteristics of Amyand's hernia (AH) in neonates in order to decrease the complications and to improve the prognosis.Methods Data about neonates with AH in Department of Neonatal Surgery,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,were collected from January 2010 to February 2017,and the AH cases published from 1997 to 2017 in PubMed and Wanfang Data were also reviewed.Results Twenty-two cases were collected,including 8 cases treated in Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,and 14 cases from literature reports.In this group,4 cases underwent traditional operation and 4 cases underwent laparoscopy,respectively.All the patients underwent appendix resection and the ligation of the hernia sac.Among the 4 cases who underwent laparoscopic operation,contra-lateral hernia was found in 2 cases and pyocelia in 1 case.However,the appendix had a solid adhesion with the inguinal canal in those 4 cases and it was difficult to return the appendix to the cavity.Thus,the laparoscopy had to be terminated and the traditional procedure was carried out to separate the adhesion.In those 4 cases to whom the traditional operation was applied,1 case presented inflammation in abdomen and the contra-lateral hernia after operation.According to the pathological results of appendix,in this group,there were 3 cases,4 cases,and 1 case that presented Ⅱ,Ⅲ,Ⅳ type,respectively.In literature cases,there were 13 cases and 1 case that underwent traditional operation and laparoscopy,respectively.There were 4 cases,9 cases,and 1 case that presented Ⅱ,Ⅲ,Ⅳ type,respectively.The complications included located peritonitis (1 case),testicular torsion (1 case) and orchitis (1 case).All cases recovered smoothly.Conclusion Most of the AH cases in neonates present appendix suppuration,gangrene or perforation.The neonatal cases with AH also present obvious local infection and they are prone to develop into pyocelia in inguinal canal and abdominal cavity.In AH cases,laparoscopy has its own advantages,which not only help to make it clear if there is the contralateral hernia,but also helps to treat the complicated pyocelia in abdominal cavity,which help to avoid the residual infection efficiently.

Objective To evaluate the efficacy and safety of single bolus high dose (SD group) ATG-Fresenius induction therapy in kidney transplantation vs.multiple low dose (MD group) administration.Methods A multiple center,prospective,randomized and controlled clinical study was performed on 280 de novo renal transplant recipients from 19 centers.Patients were randomized into 2 groups as follows:SD group,a single high dose (7-9 mg/kg) of ATG-F infused as an induction agent before the vessel anastomoses;MD group,2 mg/kg of ATG-F daily administrated in postoperative 4 days.All the patients accepted maintenance immunosuppressive protocol including tacrolimus,mycophenolate and prednisone.Patients were assessed and data were collected at regular schedule clinic visits on the day 1,3,7,14,30,90,180,270 and 365.The primary end point of efficacy was therapeutic failure rate [the number of death,grafts loss and acute rejection (AR)].The event first occurred should be used in the classification of patients.The non-inferiority evaluation of the two treatment regimens was done based on treatment failure rate.The secondary end points of efficacy were the incidence of AR,delayed graft function (DGF),1-year survival rate of patients and grafts,and serum creatinine at each visiting point.The indicators for safety evaluation included hemotologic variation and incidence of adverse events.Results The therapeutic failure rate in SD group was non-inferior to the MD group (17.24％ vs.23.08％).AR was the major cause of therapeutic failure and there was similar incidence of AR between SD gronp and MD group (12.07％ vs.21.37％).There was no significant difference in the incidence of DGF between SD group and MD group (12.07％ vs.6.84％,P =0.1721).The 1-year patient's survival rate and 1-year graft survival rate in SD group and MD group showed no significant difference (96.55％ vs.98.29％,P =0.6714;94.83％ vs 98.29％,P =0.2750).The serum creatinine level showed no significant differences between two groups at each visit point.There was also no significant difference in total incidence of adverse events between the two groups.In addition,there was also no statistically significant difference in the incidence of concerned and drug-related adverse events between the two groups,including infection,hemotologic abnormality,liver or renal dysfunction,gastrointestinal disorder,etc.After ATG--F administration,peripheral blood lymphocytes in the SD and the MD group immediately decreased but nearly restored to the normal level on the postoperative day 30 and 90 respectively.No severe granulocytopenia,erythropenia or thrombocytopenia occurred in both two groups.Conclusion The efficacy and safety of single high dose of ATG-F induction are non-inferior to multiple low dose ATG-F induction,moreover,single high dose of ATG-F induction is administered more conveniently and economically.