Comparison of clinical characteristics and prognostic factors in two site-specific categories of ampullary cancer

BACKGROUND Ampullary cancer is a relatively rare malignant tumor in the digestive system.Its incidence has increased in recent years.As for now,its biological characteristics have not been fully clarified.Recent studies have primarily focused on the histological classification and genetic changes,but there are fewer investigations into the differences among site-specific subgroups.The clinicopathological charac-teristics of ampullary cancer occurring in different positions have not been elucidated.Furthermore,the role of adjuvant therapy in the treatment of patients with ampullary cancer remains controversial.ampullary cancer and explore the factors affecting prognosis.METHODS A total of 356 patients who met the inclusion and exclusion criteria were enrolled.Patients were divided into ampulla of Vater cancer(AVC)and duodenal papilla cancer(DPC)based on the gross and microscopic findings.Baseline data,admission examination results,and perioperative outcomes were collected and analyzed.The Kaplan-Meier curve was used for survival analysis.Univariate and multivariate analysis was performed to explore the independent risk factors affecting the overall survival(OS)of both groups.RESULTS The preoperative total bilirubin level in patients with AVC was significantly higher than those with DPC(P=0.04).The OS for patients with DPC was 58.90±38.74 months,significantly longer than 44.31±35.90 months for patients with AVC(P<0.01).The independent risk factors affecting the OS of AVC included:Preoperative albumin level(P=0.009),total bilirubin level(P=0.017),and number of positive lymph nodes(P=0.005).For DPC,risk factors included:Age(P=0.004),tumor size(P=0.023),number of positive lymph nodes(P=0.010)and adjuvant treatment(P=0.020).Adjuvant therapy significantly improved the OS rate of patients with DPC,but not for those with AVC.CONCLUSION Patients with AVC had a shorter OS compared to those with DPC.The prognosis factors and the role of adjuvant therapy of two groups were different.

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation

BACKGROUND Radiation esophagitis(RE)is one of the most common clinical symptoms of regional lymph node radiotherapy for breast cancer.However,there are fewer studies focusing on RE caused by hypofractionated radiotherapy(HFRT).AIM To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes.METHODS Between January and December 2022,we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F.RESULTS Of the 64 patients in this study,24(37.5%)did not develop RE,29(45.3%)developed grade 1 RE(G1RE),11(17.2%)developed grade 2 RE(G2RE),and none developed grade 3 RE or higher.Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose,mean dose,relative volume 20-40,and absolute volume(AV)20-40.Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE(P<0.001).The optimal threshold for AV30 was 2.39 mL[area under the curve(AUC):0.996;sensitivity:90.9%;specificity:91.1%].The optimal threshold for AV35 was 0.71 mL(AUC:0.932;sensitivity:90.9%;specificity:83.9%).CONCLUSION AV30 and AV35 were significantly associated with G2RE.The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL,respectively.

综合考虑尺寸和应变速率的单晶Ni_(3)Al屈服强度的理论模型

为了综合考虑尺寸和应变率效应对单晶延性材料屈服强度的影响,建立基于位错形核机制的理论模型。以Ni_(3)Al为例,首先,通过分子动力学模拟结果拟合出材料参数;然后,通过材料参数构建屈服强度的理论曲面;最后,用现有实验数据检验该理论模型。通过现有第三方单晶铜和金的分子动力学和实验数据对该模型进行检验。结果表明,该模型可以跨越分子动力学和实验条件之间巨大的空间和时间差异,从而得到单晶Ni_(3)Al、铜和金的可靠力学性能。

Reperfusion after hypoxia-ischemia exacerbates brain injury with compensatory activation of the antiferroptosis system:based on a novel rat model

Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical practice.To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy,in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats.First,based on the conventional RiceVannucci model of hypoxic-ischemic encephalopathy,we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge.Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins.We also performed transmission electron microscopy and found typical characteristics of ferroptosis,including mitochondrial shrinkage,ruptured mitochondrial membranes,and reduced or absent mitochondrial cristae.Further,both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein,which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage.Finally,we found that ferroptosis-related Ferritin(Fth1)and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury.Based on these results,it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion.Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.

Occult pancreaticobiliary reflux is a pathogenic factor of some benign biliary diseases and gallbladder cancer

Background:Pancreaticobiliary maljunction(PBM)is a well-known high-risk factor for biliary malignant tumors because of constant pancreaticobiliary reflux(PBR).However,the impact of occult pancreaticobiliary reflux(OPR),which is characterized by high bile amylase levels in individuals with anatomically normal pancreaticobiliary junction,on biliary diseases remains unclear.The aim of this study was to assess the correlation between OPR and biliary diseases.Methods:We enrolled 94 consecutive patients with normal pancreaticobiliary junction and primary biliary diseases confirmed by magnetic resonance cholangiopancreatography.We prospectively collected patients’bile samples and measured bile amylase levels.We investigated the incidence of OPR and the difference in bile amylase levels among these patients and assessed the correlation between high bile amylase levels(HBAL)and benign or malignant biliary diseases,as well as the OPR risk factors.Results:The incidence of OPR was 36.6%in patients with benign biliary diseases,26.7%in those with cholangiocarcinoma and 62.5%in those with gallbladder cancer.The median bile amylase level tended to be higher in patients with gallbladder cancer than in those with benign biliary diseases,but there was no significant difference(165.5 IU/L vs.23.0 IU/L,P=0.212).The prevalence of an HBAL with bile amylase levels of 1000-7500 IU/L was similar in patients with gallbladder cancer and benign biliary diseases.However,the incidence of HBAL with bile amylase levels greater than 7500 IU/L was significantly higher in patients with gallbladder cancer than in those with benign biliary diseases(37.5%vs.4.2%,P=0.012).Multivariate logistic regression analysis revealed that choledocholithiasis was an independent risk factor for OPR.Conclusions:OPR can occur in benign and malignant biliary diseases,and it may be a pathogenic factor for some benign biliary diseases and a high-risk factor for gallbladder cancer.There is a correlation between choledocholithiasis and OPR.

Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma:A retrospective study

BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.

Prognostic value of T cell immunoglobulin and mucin-domain containing-3 expression in upper gastrointestinal tract tumors:A meta-analysis

BACKGROUND There is a lack of robust prognostic markers for upper gastrointestinal(GI)tract cancers,including esophageal,gastric,and esophagogastric junction cancers.T cell immunoglobulin and mucin-domain containing-3(TIM3)plays a key immunomodulatory role and is linked to the prognosis of various cancers.However,the significance of TIM3 in upper GI tract tumors is still uncertain.AIM To investigate the prognostic value of TIM3 expression in upper GI tract tumors.METHODS A literature search was conducted on the PubMed,Embase,and Web of Science databases for relevant studies published until June 2023.After screening and quality assessment,studies that met the criteria were included in the metaanalysis.Statistical methods were used for the pooled analysis to assess the association of TIM3 expression in upper GI tract tumors with the prognosis and clinicopathological parameters.The results were reported with the hazard ratio(HR)and 95%confidence interval(CI).RESULTS Nine studies involving 2556 patients with upper GI tract cancer were included.High TIM3 expression was associated with a worse prognosis in upper GI tract cancer(HR:1.17,95%CI:1.01-1.36).Positive expression of TIM3 in gastric cancer was correlated with the T and N stage,but the difference was not statistically significant.However,TIM3 overexpression was significantly correlated with the TNM stage(odds ratio:1.21,95%CI:0.63-2.33;P<0.05).TIM3 expression showed no association with the other clinicopathological parameters.CONCLUSION High expression of TIM3 in the upper GI tract cancer is associated with a worse prognosis and advanced T or N stages,indicating its potential value as a prognostic biomarker.These findings may provide a basis for the personalized treatment of upper GI tract cancers.

先天性心脏病合并肺动脉高压的研究进展

肺动脉高压(pulmonary arterial hypertension, PAH)是先天性心脏病(congenital heart disease, CHD)的严重并发症之一,严重影响患者的生存质量,其病死率及致残率均较高,是各类型CHD 手术方式选择和预后的关键因素。本文将从流行病学、定义和分类、评价和治疗几个方面,阐述近几年CHD 相关性PAH(PAH associatedCHD, PAH-CHD)的研究进展,并将其做一综述。

Transcatheter closure of ventricular septal defect in patients with aortic valve prolapse and mild aortic regurgitation:feasibility and preliminary outcome

Objective:To evaluate the feasibility,safety and efficacy of transcathcter closure of ventricular septal defect(VSD)in patients with aortic valve prolapse(AVP)and mild aortic regurgitation(AR).Methods:Between January 2008 and July 2014,transcatheter closure of VSD was attempted in 65 patients.Results:The total intermediate closure successful rate in all subjects was 96.9%.During the perioperative period,no death,major bleeding,pericardial tamponade,occluder dislodgement,residual shunt or hemolysis occurred.Two procedures had been forced to suspend due to significant aggregation of device related aortic regurgitation,three cases of transient complete left bundle branch block occurred but did not sustain.At 1-year followup,no patients had residual shunts and complications.Furthermore,grade of residual AR were relieved in 61.9%(39/63)cases and degree of AVP were ameliorated in 36.5%(23/63)patients;Conclusions:Transcatheter closure VSD in selected patients with AVP and mild AR is technically feasible and highly effective.Long term safety and efficacy needs to be assessed.

Application of self-care based on full-course individualized health education in patients with chronic heart failure and its influencing factors

BACKGROUND The treatment of heart failure not only needs to relieve the clinical symptoms and improve the quality of life for patients but also needs to select scientific and reasonable ways to prevent or delay the progression of the disease,thus reducing the mortality and hospitalization rate.Although the previous regimen can effectively relieve symptoms in the early stage of treatment,long-term use may cause adverse events,such as arrhythmia,and even increase mortality.Therefore,conventional treatment cannot meet the actual health needs of patients,and scientific nursing intervention is very necessary.AIM To investigate the application of self-care based on full-course individualized health education (FCIHE) and its influencing factors in patients with chronic heart failure (CHF).METHODS We enrolled CHF patients who were admitted to our center between September 2015 and June 2016 and divided them into an intervention group (n = 50) and control group (n = 50) using a random number table.Routine nursing care was applied to the control group,and FCIHE was offered to the intervention group.The self-care behavior,6-min walking distance (6MWD),and 36-item short form health survey (SF-36) scores were compared between the two groups.The influencing factors of the self-care were also analyzed.RESULTS The 6MWD was not significantly different between the two groups at admission (P > 0.05);however,at 3 and 6 mo after discharge,6MWD was significantly increased,and it was significantly longer in the intervention group (P < 0.05).The scores for self-care behavior showed no significant difference at admission between the two groups (P > 0.05);however,at 3 and 6 mo after discharge,the total scores for self-care maintenance,management,confidence,and behavior of the intervention group were significantly higher than those of the control group (P < 0.05).There were no significant differences in the SF-36 scores at admission (P > 0.05);however,at 3 mo and 6 mo after discharge,the scores for all eight subscales,including physical functioning,role limitations due to physical problems,bodily pain,general health perceptions,vitality,social functioning,role-limitations due to emotional problems,and mental health,were significantly higher in the intervention group (P < 0.05).As shown by logistic regression analysis,the influencing factors of self-care mainly included age,cardiac function class,and education background (odds ratio > 1;all P < 0.05).CONCLUSION FCIHE improved self-care behavior and cardiac function in CHF patients.Age,cardiac function,and education level affected the implementation of self-care among CHF patients.

Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion:A prospective cohort study

BACKGROUND The long-term effect of anatomic resection(AR)is better than that of nonanatomic resection(NAR).At present,there is no study on microvascular invasion(MVI)and liver resection types.AIM To explore whether AR improves long-term survival in patients with hepatocellular carcinoma(HCC)by removing the peritumoral MVI.METHODS A total of 217 patients diagnosed with HCC were enrolled in the study.The surgical margin was routinely measured.According to the stratification of different tumor diameters,patients were divided into the following groups:≤2 cm group,2-5 cm group,and>5 cm group.RESULTS In the 2-5 cm diameter group,the overall survival(OS)of MVI positive patients was significantly better than that of MVI negative patients(P=0.031).For the MVI positive patients,there was a statistically significant difference between AR and NAR(P=0.027).AR leads to a wider surgical margin than NAR(2.0±2.3 cm vs 0.7±0.5 cm,P<0.001).In the groups with tumor diameters<2 cm,both AR and NAR can obtain a wide surgical margin,and the surgical margins of AR are wider than that of NAR(3.5±5.8 cm vs 1.6±0.5 cm,P=0.048).In the groups with tumor diameters>5 cm,both AR and NAR fail to obtain wide surgical margin(0.6±1.0 cm vs 0.7±0.4 cm,P=0.491).CONCLUSION For patients with a tumor diameter of 2-5 cm,AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin,reduce postoperative recurrence,and improve prognosis.

Early Versus Delayed Laparoscopic Cholecystectomy for Acute Cholecystitis with Mild Pancreatitis

The safety and feasibility of early laparoscopic cholecystectomy(LC)for acute cholecystitis with mild pancreatitis were explored.A total of 973 patients with acute pancreatitis,including 651 mild cases and 322 moderate or severe cases were retrospectively studied from July 2014 to December 2018 in our department.And 426 mild pancreatitis cases with acute cholecystitis were enrolled in this study,of which 328 patients underwent LC during the same-admission(early LC group),and 98 patients underwent LC a period of time after conservative treatment(delayed LC group).Clinical characteristics,operative findings and complications were recorded and followed up.The two groups were comparable in age,gender,the grade of American Society of Anesthesiologist(ASA),biochemical findings and Balthazar computer tomography(CT)rating(P>0.05).The operation interval and hospital stay in early LC group were significantly shorter than in delayed LC group(5.83+1.62 vs.41.3618.44 days;11.38+2.43 vs.16.49+3.48 days,P<0.01).There was no significant difference in the average operation time between the two groups.No preoperative biliary related events recurred in early LC group but there were 21 cases of preoperative biliary related events in delayed LC group(P<0.01).There was no significant difference in conversion rate(3.85 vs.5.10%,P=0.41)and surgical complication rate(3.95 vs.4.08%,P-0.95)between early LC group and delayed LC group.During the postoperative follow-up period of 375 cases,biliary related events recurred in 4 cases in early LC group and 3 cases in delayed LC group(P=0.37).The effect of early LC during the same-admission is better than delayed LC for acute cholecystitis with mild pancreatitis.

Synergistic effect of bromocriptine and tumor necrosis factor-a on reversing hepatoceiiuiar carcinoma multidrug resistance in nude mouse MDRl model of liver neoplasm

AIM： To investigate the effect of bromocripUne （BCT） and tumor necrosis factor-α ClNF-α） on hepatocellular carcinoma （HCC） multidrug resistance （MDR） in nude mouse HDR model of liver neoplasm. METHODS： Human hepatocarcinoma cell line HepG2t drug resistant hepatocarcinoma cell line HepG2/adriamycin （ADM） and hepatocarcinoma cell line transfected with TNF-α gene HepG2JADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established （HepG2t ADM, TNF, BCT groups）. Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor his^logical character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins （MRP, LRP） of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS： The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group （67%） compared to ADM and TNF groups, and similar to HepG2group （54%）. MDRI and LRPmRNA could be detected in all groups, but TNF-α was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay. CONCLUSION： BCT and TNF-a can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm. 2005 The WJG Press and Elsevier Inc. All rights reserved

Systemic changes and adverse effects induced by retinopathy of prematurity screening

AIM: To estimate the potential systemic events during and after retinopathy of prematurity (ROP) screening. ' METHODS: A prospective and descriptive designed study was conducted to detect the physiologic and pathological changes 24h before, during, and 72h after ROP screening. Control blood pressure (BP), saturation, pulse rate, and body temperature were routinely taken at various time internals before and after screening. Adverse effects pertain to cardiovascular system, respiratory system, gastric system, urinary system and nervous system were retrospect 0-72h after ROP screening at a 24-hour interval. RESULTS: Totally 1254 prematurity babies receiving ROP screening during Jan. 1st 2013 to Dec. 31th 2013 were enrolled in our survey. Compared to control vital sign data taken before the examination, there was a fluctuation in the diastolic BP with the increased 3.03 mm Hg (P=0.04) after 3 doses of mydriatic drops. Immediately after the examination, there was a further 12.64 mm Hg (P<0.01) increase in systolic BP and a 7.24 mm Hg (P<0.01) in diastolic BP. The mean pulse rate during examination was 22.4 bpm (P<0.01) higher than the 133.3 +/- 9.0 bpm control level. The oxygen saturation shared an average drop of 5% (P<0.01) during screening. In prematurity with postconceptional age less than 31wk, the incidence of apnea (23.5%), necrotizing enterocolitis (NEC) (8.7%), gastric residual (25.4%) and upper digestive tract hemorrhage (6.4%) also demonstrated a significant rise (P<0.01). CONCLUSION: In our study sample, ROP screening was associated with NEC, gastric residual and upper digestive tract hemorrhage. These gastrointestinal side effects, along with breath activity pattern change and vital signs indicators fluctuation, may be results of additional stress responses.

Deep learning-based radiomics based on contrast-enhanced ultrasound predicts early recurrence and survival outcome in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver malignancy.AIM To predict early recurrence(ER)and overall survival(OS)in patients with HCC after radical resection using deep learning-based radiomics(DLR).METHODS A total of 414 consecutive patients with HCC who underwent surgical resection with available preoperative grayscale and contrast-enhanced ultrasound images were enrolled.The clinical,DLR,and clinical+DLR models were then designed to predict ER and OS.RESULTS The DLR model for predicting ER showed satisfactory clinical benefits[area under the curve(AUC=0.819 and 0.568 in the training and testing cohorts,respectively)],similar to the clinical model(AUC=0.580 and 0.520 in the training and testing cohorts,respectively;P>0.05).The C-index of the clinical+DLR model in the prediction of OS in the training and testing cohorts was 0.800 and 0.759,respectively.The clinical+DLR model and the DLR model outperformed the clinical model in the training and testing cohorts(P<0.001 for all).We divided patients into four categories by dichotomizing predicted ER and OS.For patients in class 1(high ER rate and low risk of OS),retreatment(microwave ablation)after recurrence was associated with improved survival(hazard ratio=7.895,P=0.005).CONCLUSION Compared to the clinical model,the clinical+DLR model significantly improves the accuracy of predicting OS in HCC patients after radical resection.

Diagnosis and Treatment of Cholangiocarcinoma: A Consensus from Surgical Specialists of China

Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.

Postoperative outcomes and recurrence patterns of intermediatestage hepatocellular carcinoma dictated by the sum of tumor size and number

BACKGROUND The selection criteria for Barcelona Clinic Liver Cancer(BCLC)intermediate-stage hepatocellular carcinoma(HCC)patients who would truly benefit from liver resection(LR)remain undefined.AIM To identify BCLC-B HCC patients more suitable for LR.METHODS We included patients undergoing curative LR for BCLC stage A or B multinodular HCC(MNHCC)and stratified BCLC-B patients by the sum of tumor size and number(N+S).Overall survival(OS),recurrence-free survival(RFS),recurrence-to-death survival(RTDS),recurrence patterns,and treatments after recurrence in BCLC-B patients in each subgroup were compared with those in BCLC-A patients.RESULTS In total,143 patients who underwent curative LR for MNHCC with BCLC-A(n=25)or BCLC-B(n=118)were retrospectively analyzed.According to the N+S,patients with BCLC-B HCC were divided into two subgroups:BCLC-B1(N+S≤10,n=83)and BCLC-B2(N+S>10,n=35).Compared with BCLC-B2 patients,those with BCLC-B1 had a better OS(5-year OS rate:67.4%vs 33.6%;P<0.001),which was comparable to that in BCLC-A patients(5-year OS rate:67.4%vs 74.1%;P=0.250),and a better RFS(median RFS:19 mo vs 7 mo;P<0.001),which was worse than that in BCLC-A patients(median RFS:19 mo vs 48 mo;P=0.022).Further analysis of patients who developed recurrence showed that both BCLC-B1 and BCLC-A patients had better RTDS(median RTDS:Not reached vs 49 mo;P=0.599),while the RTDS in BCLC-B2 patients was worse(median RTDS:16 mo vs not reached,P<0.001;16 mo vs 49 mo,P=0.042).The recurrence patterns were similar between BCLC-B1 and BCLC-A patients,but BCLC-B2 patients had a shorter recurrence time and a higher proportion of patients had recurrence with macrovascular invasion and/or extrahepatic metastasis,both of which were independent risk factors for RTDS.CONCLUSION BCLC-B HCC patients undergoing hepatectomy with N+S≤10 had mild recurrence patterns and excellent OS similar to those in BCLC-A MNHCC patients,and LR should be considered in these patients.

Long-term testosterone supplementation is useful for ED Nith testosterone deficiency

Dear Editor, We present an interesting case of a patient with erectile dysfunction （ED） and testosterone deficiency （TD） who was treated with testoster- one supplementation therapy （TST） in combination with sildenafil for 45 months. The patient continued to respond well even after the discontinuation of sildenafil for 8 months. Major side effects and complications were not reported at the long-term follow-up.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment

Androgenetic alopecia(AGA),the most prevalent clinical hair loss,lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients.In this study,a hyaluronic acid(HA)based hydrogel-formed microneedle(MN)was designed,referred to as V-R-MNs,which was simultaneously loaded with vascular endothelial growth factor(VEGF)and the novel hair loss drug Ritlecitinib,the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates(PHAs)nanoparticles(R-PHA NPs)for minimally invasive AGA treatment.The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency.Due to the biosafety,mechanical strength,and controlled degradation properties of HA hydrogel formed microneedles,V-R-MNs can effectively penetrate the skin’s stratum corneum,facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive,painless and long-term sustained release manner.V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells,but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis.In comparison to the clinical drug minoxidil for AGA treatment,the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase,improved hair quality,and greater coverage.This introduces a new,clinically safer,and more efficient strategy for AGA treatment,and serving as a reference for the treatment of other related diseases.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study

Background:Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma(HCC)patients.The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure(PHLF)remains poorly defined.This study aimed to construct and validate a combined pre-and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center’s data.Methods:Consecutive HCC patients who underwent hepatectomy between May 18,2019 and Dec 19,2020 were enrolled at five tertiary hospitals.Preoperative cirrhotic severity scoring(CSS)and intra-operative direct liver stiffness measurement(DSM)were performed to correlate with the Laennec histopathological grading system.The performances of the pre-operative nomogram and combined pre-and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF.Results:For 327 patients in this study,histopathological studies showed the rates of HCC patients with no,mild,moderate,and severe cirrhosis were 41.9%,29.1%,22.9%,and 6.1%,respectively.Either CSS or DSM was closely correlated with histopathological stages of cirrhosis.Thirty-three(10.1%)patients developed PHLF.The 30-and 90-day mortality rates were 0.9%.Multivariate regression analysis showed four pre-operative variables[HBV-DNA level,ICG-R15,prothrombin time(PT),and CSS],and one intra-operative variable(DSM)to be independent risk factors of PHLF.The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin.The combined pre-and intra-operative nomogram was constructed by adding the intra-operative DSM.The pre-operative nomogram was better than the conventional models in predicting PHLF.The prediction was further improved with the combined pre-and intra-operative nomogram.Conclusions:The combined pre-and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram.