Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:This study aims to systematically compare the differences in severity, clinical manifestations, and treatment processes between patients with foodborne and iatrogenic botulism, thereby providing evidence-based support for clinical diagnosis and management.Methods:A retrospective analysis was conducted on botulism patients admitted to the Second Hospital of Hebei Medical University between January 2010 and July 2024. The foodborne group was diagnosed according to the WS/T 83-1996 standard. The iatrogenic group required a documented history of type A botulinum toxin injection and typical clinical manifestations. Individuals with comorbid neurological disorders or incomplete clinical data were excluded. The severity of poisoning was classified into three groups: mild, moderate, and severe, according to the "Diagnosis and Treatment Protocol for Botulism". SPSS 26.0 software was used to statistically analyze the distribution of poisoning severity between groups and to compare clinical symptoms and course indicators across severity grades.Results:A total of 220 botulism patients were included in this study, comprising 86 cases of foodborne poisoning (39.1%) and 134 cases of iatrogenic poisoning (60.9%). There was a significant difference in the distribution of poisoning severity between the two groups ( P=0.001), the proportion of severe poisoning was significantly higher in the foodborne group. Analysis of clinical symptoms indicated that, among patients with mild poisoning, the incidence of nausea and vomiting was significantly higher in the foodborne group, compared to that in the iatrogenic group (44.0% vs. 16.4%, P=0.006). In patients with moderate poisoning, the iatrogenic group exhibited a significantly higher prevalence of hoarseness (60.5% vs. 35.7%, P=0.041) and neck weakness (53.5% vs. 17.9%, P=0.003) compared to the foodborne group. Conversely, the foodborne cohort experienced a notably longer interval before seeking medical attention when compared to their iatrogenic counterparts (2.25 d vs. 1.50 d, P=0.003). Among severe poisoning patients, the foodborne group exhibited a higher likelihood of experiencing fever (51.5% vs. 25.0%, P=0.044) and abdominal distension accompanied by constipation (69.7% vs. 41.7%, P=0.034) when compared to the iatrogenic group. Furthermore, the foodborne cohort demonstrated a significantly shorter incubation period (1.00 d vs. 2.45 d, P<0.001), an extended length of hospitalization (22.0 d vs. 16.00 d, P=0.001), and a prolonged duration of antitoxin therapy (14.00 d vs. 9.50 d, P<0.001), alongside a markedly higher total dosage administered (315 900 U vs. 163 300 U, P<0.001) compared to their iatrogenic counterparts. Conclusions:Statistically significant differences exist between food-borne and iatrogenic botulism. Food-borne botulism is characterized by acute onset, greater severity, and a prolonged course, predominantly featuring systemic symptoms and gastrointestinal dysfunction. In contrast, iatrogenic botulism primarily manifests with ocular and oropharyngeal muscle symptoms and is generally less severe.

Super-pulse thulium fiber laser (hereinafter referred to as thulium laser) has shown broad application prospects in medical research, especially in the treatment of urinary tract stones.Thulium laser has a thin fiber diameter, which reduces the occupation of the working channel and increases the irrigation water flow.Currently, the peak power reaches up to 500 W, the single pulse energy to 6 J, and the frequency to 2000 Hz.The stone-breaking mechanism of thulium laser is photothermal and photomechanical.Different combinations of energy and frequency will significantly affect the volume of stone fragments. "High energy and low frequency" is more suitable for "fragmentation" stone breaking, while "low energy and high frequency" is more suitable for "powderization" stone breaking.Some in vitro experiments have confirmed that thulium laser has higher stone-breaking efficiency, less stone displacement, and more obvious thermal effects compared to holmium laser.Clinically, thulium laser has been applied to ureteroscopic lithotripsy and percutaneous nephrolithotomy., and the stone free rate and safety are relatively high.This article reviews the stone-breaking principles, in vitro experiments, and clinical applications of thulium laser, aiming to provide better theoretical support and practical experience for the development and application of super-pulse thulium fiber laser in the future.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective The aim of this study was to investigate the molecular regulatory mechanism of cancer susceptibility candidate 15(CASC15),a long-stranded non-coding RNA(lncRNA),in hepatocellular carcinoma(HCC).Methods Bioinformat-ics methods were used to predict the expression of target genes and analyze the relationship between the expression of target genes and the survival time of patients;Hepatocellular carcinoma tissues and adjacent tissues from patients with HCC were collected;CCK-8,Tr-answell,and flow cytometry experiments were used to detect proliferation,invasion,migration and apoptosis of SMMC7721 cells and Huh-7 cells;The dual-luciferase assay was used to detect the targeting relationship between miR-144-3p and CASC15,as well as leucine rich repeat containing protein 1(LRRC1);RT-qPCR and Western blot were used to detect mRNA and protein expression of target genes;Immunofluorescence was used for protein localization of target genes;Replicate experiment was performed to verify the effect of CASC15/miR-144-3p/LRRC1 on the progression of HCC.In vivo experiment was performed to verify the effect of CASC15 on HCC progression.Results TCGA database and RT-qPCR assay showed high expression of CASC15,low expression of miR-144-3p,and high expression of LRRC1 in HCC tissues and cells(P<0.05).The results of cell function experiments on proliferation,inva-sion and migration showed that CASC15 and LRRC1 played a promoting role in tumor development,while miR-144-3p had an inhibi-tory effect,consistent with the results of apoptosis experiments(P<0.05).Cell function experiments showed that CASC15 inhibited miR-144-3p function,miR-144-3p inhibited LRRC1,and CASC15 bound to miR-144-3p,leading to the upregulation of LRRC1.The replicate experimental results indicated that CASC15 promoted LRRC1 expression through inhibiting miR-144-3p,thereby pro-moting HCC cell proliferation,invasion and migration,and inhibiting apoptosis.Conclusion CASC15 may promote HCC progression by regulating the miR-144-3p/LRRC1 axis.

Objective:To investigate the impact of age,various hormonal levels,and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction(ED).Me-thods:A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography(CDDU)and intracavernosal injection test(ICI)at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023.Data were managed and processed using SPSS 29.0,and a multivariable Logistic regression analysis was conducted.Results:A total of 700 ED patients were included,with 380 showing negative ICI results and 320 positive.In the study,84 patients had a peak systolic velocity(PSV)＜25 cm/s,while 616 had PSV ≥ 25 cm/s;202 patients had end-diastolic velocity(EDV)＞5 cm/s,and 498 had EDV ≤5 cm/s.264 patients had ab-normal PSV and/or EDV results,and 436 had normal results for both.Patients with vascular ED had sig-nificantly lower estrogen levels(t=-3.546,P＜0.001),lower testosterone levels(t=-2.089,P=0.037),and a higher rate of hyperglycemia(x2=12.772,P=0.002)compared with those with non-vascular ED.The patients with arterial ED were older(t=3.953,P＜0.001),had a higher rate of hyperglycemia(x2=9.518,P=0.009),and a higher estrogen/testosterone ratio(t=2.330,P=0.020)compared with those with non-arterial ED.The patients with mixed arteriovenous ED had higher age(t=3.567,P＜0.001),lower testosterone levels(t=-2.288,P=0.022),a higher rate of hyperglycemia(x2=12.877,P=0.002),and a larger estrogen/testosterone ratio(t=2.096,P=0.037)compared with those with normal findings.Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED(OR=1.009,95％CI:1.004-1.014),and glucose 7.0 mmol/L was a risk factor(OR=0.381,95％CI:0.219-0.661).Older age was a risk factor for arte-rial ED(OR=0.960,95％CI:0.938-0.982).Additionally,older age(OR=0.976,95％CI:0.958-0.993)and glucose levels of 5.6-6.9 mmol/L(OR=0.591,95％CI:0.399-0.876)were also risk fac-tors for mixed arterio-venous ED.Conclusion:Hyperglycemia and aging may impair penile cavernous body vascular function,while higher levels of estrogen may have a protective effect on it.

The studies on infectiousness of person infected with SARS-CoV-2 at different stages of illness are an important basis for making effective prevention and control measures such as investigating the infectious source, determining the scope of close contacts and the timing of case isolation. This review discusses the infectiousness of cases infected with SARS-CoV-2 in the incubation period, symptomatic period and convalescent period by reviewing national and international literatures, technical and professional guidelines. Existing researches suggest that the infectious viruses could be isolated at the end of the incubation period as well as since illness onset, and viral load in upper respiratory tract swabs reached the peak on day 4-6 after illness onset and thereafter began to decline, implying the infectiousness was relatively strong at the end of incubation period and within one week after illness onset. Although there were a few cases who tested positive for SARS-CoV-2 after recovery, no evidence was found to indicate these cases can cause the transmission.

Objective: To explore the effect of circ_0005075 on the proliferation and invasion of liver cancer cells and its underlying mechanism. Methods:Atotal of 35 cases of cancer tissues and corresponding para-cancerous tissues from liver cancer patients, who underwent surgical resection in Tangshan Workers’Hospital from March 2015 to March 2018, were collected for this study. qPCR was used to detect the expression levels of circ_0005075 and miR-335 in liver cancer tissues, para-cancerous tissues, liver cancer cell lines (HCCC9810, HepG2, HLE and hepatic epithelial THLE-3 cells). Dual luciferase reporter gene assay was used to verify the targeting relationship among circ 0005075, mir-335 and CCND1. By using liposome-mediated method, Sh-circ_0005075, miR-335 mimics, miR335 mimics+pcDNA-CCND1, sh-circ_0005075+pcDNA-CCND1, pcDNA-circ_0005075+miR-335 mimics, sh-CCND1+pcDNA-circ_ 0005075 were transfected into HCCC9810 cells, respectively. The effects of circ_0005075/miR-335/CCND1 molecular axis on the proliferation and invasion of HCCC9810 cells were detected by MTT and Transwell methods. Results: circ_0005075 was highly expressed in liver cancer tissues and cell lines (P<0.01) ,and the highest expression in HCCC9810 cells (P<0.05). Dual luciferase reporter gene results showed that circ_0005075 negatively regulated miR-335 (P<0.05), and CCND1 was a target gene of miR-335 (P<0.05). Further experiments proved that knockdown of circ_0005075 or overexpression of miR-335 could inhibit the proliferation and invasion of HCCC9810 cells by regulating CCND1（P<0.05 or P<0.01） . Conclusion: Circ_0005075 upregulates the expression level of CCND1 by sponging miR-335, thereby promoting the proliferation and invasion of HCCC9810 cells.

Objective Toinvestigatethediagnosticvalueof3DGSPACEsequencewith3Dreconstructiontechniqueinevaluationof posterolateralcomplexofthekneejoint.Methods 30kneejointsofhealthyvolunteersweresubjectedtoMRIconventionalsequences andSPACEsequencewith3Dreconstructiontechnique.AdoubleblindmethodwasusedtocompareMRIroutineand3DGSPACEsequence imagesontheposteriorlateralcomplexofthekneejoint.Theeffectoftwoscanningmethodsonthelateralcollateralligament,popliteal tendonandpoplitealligamentwasanalyzedbyrankandtest.Results Ithadstatisticaldifferencebetweentwogroupsindisplayof posterolateralcomplex(P＜0.01).Thedisplayeffecton3DGSPACEsequenceforthelateralcollateralligament,poplitealtendonand poplitealligamentwasbetterthanthatontheconventionalMRIsequence.Conclusion 3DGSPACEsequencewith3Dreconstruction techniquecancompletelydisplaytheconfigurationanddirectionofposterolateralcomplex,whichcanimprovetherateofshowingligament obviously.

AIM: To investigate the effect of GSTP1 over-expression on the sensitivity of human hepatoma HepG2 cells to oxaliplatin (OXA).METHODS: Adenovirus carrying GSTP1 (Ad-GSTP1) was used to infect HepG2 cells for establishing the cell line over-expressing GSTP1.The cells were randomly divided into 6 groups: control, vehicle, Ad-GSTP1, OXA, OXA +vehicle and OXA +Ad-GSTP1.The cell survival rates were examined by CCK-8 assay, and the apoptotic rates were analyzed by flow cytometry.The protein levels of GSTP1, Akt, mTOR, p-Akt and p-mTOR were deter-mined by Western blot.RESULTS: OXA decreased the cell survival rate in a dose-dependent manner (P <0.05).The protein expression of GSTP1 increased after transfection with adenovirus.At basal level, up-regulation of GSTP1 signifi-cantly decreased the cell survival rate, increased the cell apoptosis, and inhibited the phosphorylation levels of Akt and mTOR (P <0.05).Moreover, GSTP1 over-expression enhanced the effect of OXA on the cell viability, cell apoptosis, and further inhibited the phosphorylation levels of Akt and mTOR ( P <0.05).CONCLUSION: Over-expression of GSTP1 augments the enhanced effect of OXA on HepG2 cell apoptosis, which may be related to the inactivation of Akt/mTOR signaling pathway.