Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)

Guidelines for the prevention and treatment of chronic hepatitis B(2022 edition)expanded the indications for antiviral therapy in patients with chronic hepatitis B.The guidelines recommend to initiate antiviral therapy for patients with chronic HBV infection who have a normal alanine aminotransferase(ALT)level,positive HBV DNA,and an age of>30 years.However,for pregnant women aged>30 years,no consensus has been reached on whether to start antiviral therapy immediately.Some experts believe that pregnant women with a normal ALT level are mostly in the immune-tolerant phase,and antiviral therapy tends to have an unsatisfactory therapeutic effect;in addition,medication during pregnancy may affect the safety of mothers and fetuses.Therefore,it is not recommended to start antiviral therapy immediately in early pregnancy even if the pregnant women are aged>30 years.Other experts believe that immune changes of the body during pregnancy may be a special period for HBV immune clearance,and if the patients are aged>30 years,antiviral therapy should be initiated immediately even if the patient has a normal ALT level;pregnant women may get better virologic and even serological response.With a focus on the above issues,this article elaborates on the purpose,treatment timing,and drug withdrawal timing of antiviral therapy during pregnancy.

Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus leaves.The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)calculations.Notably,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers.Additionally,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 cells.Compounds 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with paraptosis.Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the MAPK signaling pathway.

Objective:To investigate the dynamic changes of diaphragm and limb skeletal muscle in patients with sepsis by bedside ultrasound and their correlation with the ratio of blood urea/creatinine ratio (UCR) in 7 days after intensive care unit (ICU) admission.Methods:A prospective observational study was conducted. A total of 55 patients with sepsis admitted to ICU of General Hospital of Ningxia Medical University from June 2022 to February 2023 were selected as the research objects. General information, laboratory indicators [urea, serum creatinine (SCr), and UCR] on days 1, 4, and 7 of ICU admission, and prognostic indicators were observed. Bedside ultrasound was used to assess the dynamic changes of diaphragm morphology [including diaphragmatic excursion (DE), end-inspiratory diaphragm thickness (DTei), and end-expiratory diaphragm thickness (DTee)] on days 1, 4, and 7 of ICU admission, as well as limb skeletal muscle (quadriceps femoris) morphology [including rectus femoris-muscle layer thickness (RF-MLT), vastus intermedius-muscle layer thickness (VI-MLT), and rectus femoris-cross sectional area (RF-CSA)]. Diaphragm thickening fraction (DTF) and RF-CSA atrophy rate were calculated, and the incidence of diaphragm and limb skeletal muscle dysfunction was recorded. The correlation between ultrasound morphological parameters of diaphragm and quadriceps and UCR at each time points in 7 days after ICU admission was analyzed by Pearson correlation.Results:A total of 55 patients with sepsis were included, of which 29 were in septic shock. As the duration of ICU admission increased, the incidence of diaphragm dysfunction in patients with sepsis increased first and then decreased (63.6%, 69.6%, and 58.6% on days 1, 4, and 7 of ICU admission, respectively), while the incidence of limb skeletal muscle dysfunction showed an increasing trend (54.3% and 62.1% on days 4 and 7 of ICU admission, respectively), with a probability of simultaneous occurrence on days 4 and 7 of ICU admission were 32.6% and 34.5%, respectively. The UCR on day 7 of ICU admission was significantly higher than that on day 1 [121.77 (95.46, 164.55) vs. 97.00 (70.26, 130.50)], and RF-CSA atrophy rate on day 7 was significantly higher than that on day 4 [%: -39.7 (-52.4, -22.1) vs. -26.5 (-40.2, -16.4)]. RF-CSA was significantly lower on day 7 compared to day 1 [cm 2: 1.3 (1.0, 2.5) vs. 2.1 (1.7, 2.9)], with all differences being statistically significant (all P < 0.05). Pearson correlation analysis showed that RF-CSA on day 7 of ICU admission was negatively associated with the UCR on the same day ( r = -0.407, P = 0.029). Conclusions:Diaphragmatic dysfunction in patients with sepsis occurred early and can be improved. Limb skeletal muscle dysfunction occurred relatively later and progresses progressively. The RF-CSA on day 7 of ICU admission may be a reliable measure of limb skeletal muscle dysfunction in patients with sepsis, can be an indicator of early identification and diagnosis of ICU-acquired weakness (ICU-AW). Continuous loss of muscle mass occurring in septic patients is mainly associated with persistent organismal catabolism, and undergoes significant changes around a week in ICU.

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

Objective : To investigate possible functional disorders of central auditory processing and language in school-age children with cleft palate through an assessment of the characteristics of the P300 and N400 event-related potentials (ERPs). Methods : This study included 28 school-age children with cleft palate, aged 6 to 12 years, and 30 children without cleft palate as a control group. The P300 and N400 ERPs were selected as indexes of the central auditory processing and language functions of children in both groups. The data were statistically compared between the two groups. Results : Compared with the controls, the children with cleft palate showed a significantly prolonged P300 latency (331.73 ± 14.94 ms vs. 348.64 ± 14.66 ms, P < 0.05) and a significantly decreased P300 amplitude (13.47 ± 2.24 μV vs. 12.07 ± 2.46 μV, P < 0.05). Similarly, the N400 latency of children with cleft palate was significantly prolonged compared to that of controls (431.07 ± 17.90 ms vs. 408.23 ± 18.04 ms, P < 0.05), and the N400 amplitude was significantly decreased compared to that of controls (13.75 ± 2.12 μV vs. 15.17 ± 2.34 μV, P < 0.05). Conclusion School-age children with cleft palate may have central auditory processing disorders and language dysfunctions.

Objective To investigate the clinical features and prognosis related risk factors in nonalcoholic steatosis liver cirrhosis(NASLC).Methods From January 1st,2006 to December 31st, 2013,in a prospective cohort of 12 489 patients with liver cirrhosis set,174 patients were with NASLC and 306 patients with hepatitis B were the control.The patients were followed up every three months. The clinical data of patients were collected,including gender,age,height,body weight,blood pressure, history of hypertension,history of diabetes,family history of tumor,blood glucose level,high density lipoprotein cholesterol(HDL-C)level,low density lipoprotein cholesterol(LDL-C)level,triglyceride level,white blood cell,platelet,prothrombin time activity,total bilirubin,albumin,cholinesterase,blood urea nitrogen,creatinine,alpha-fetoprotein,abdominal ultrasound,abdominal computer tomography and endoscopy.Body mass index(BMI)and Child-Pugh scores were calculated.The differences between the two groups were analyzed in the incidence of ascites,hepatic encephalopathy,hepatorenal syndrome, esophageal varices bleeding,liver failure,hepatocellular carcinoma and mortality.Chi square test and t test were performed for statistical analysis.logistic regression analysis was used to analyze the risk factors associated with hepatocellular carcinoma in patients with NASLC.Results The proportion of female in NASLC group was higher than that in posthepatic cirrhosis group(56.0%,47/84 vs 28.7%,49/171), and the difference was statistically significant(χ2 =17.653,P<0.01).BMI,systolic pressure,diastolic pressure,level of fasting blood glucose,LDL-C,triglyceride,prothrombin time activity,albumin, cholinesterase,cases number of hypertension,diabetes and metabolic syndrome of NASLC group were all significantly higher than those of posthepatic cirrhosis group(t=6.267,4.091,5.773,2.914,1.877, 2.044,2.326,1.935 and 2.023;χ2=7.241,9.399 and 81.367;all P<0.05),however,serum levels of HDL-C,total bilirubin and creatinine were significantly lower than those of posthepatic cirrhosis group (t=6.127,8.487 and 3.261;all P < 0.05).T he three-year accumulative incidences of hepatic encephalopathy,hepatorenal syndrome and liver failure of NASLC group(8.3%,7/84;1.2%,1/84;0) were all lower than those of posthepatic cirrhosis control group(22.2%,38/171;9.9%,17/171 and 5.8%, 10/171;χ2 = 5.751,3.862 and 3.927,all P< 0.05).The three-year accumulative incidence of hepatocellular carcinoma of NASLC was 8.3%(7/84).The three-year accumulative incidence of mortality was lower than that of posthepatic cirrhosis group(2.4%,2/84 vs 13.5%,23/171;χ2 = 3.884,P=0.049).The results of logistic regression analysis showed that BMI(odds ratio(OR)= 1.469,95%confidence interval(CI)1.093 to 2.176,P=0.016)and diabetes(OR=1.734,95% CI 1.269 to 2.388, P=0.012)were independent risk factors associated with hepatocellular carcinoma in NASLC patients. Conclusions NASLC occurrs mainly in female with good liver function.BMI and diabetes are the risk factors associated with hepatocellular carcinoma in patients with NASLC.

Small cell carcinoma of cervix (SCCC) is a rare disease with highly aggressive behaviour and is pathologically hard to diagnose. In this study, the clinicopathological features, diagnosis, treatment and prognosis of the condition were examined. Clinical records and follow-up data of 7 cases of SCCC were retrospectively studied. Our results showed that five non-recurrent cases initially presented irregular vaginal bleeding or increased apocenosis of varying degrees. Pathological examination revealed that the stroma was diffusely infiltrated with small monomorphous cells ranging from round to oval shape. Three cases were immunohistochemically confirmed. One case was accompanied with squamous cell cancer. Of the 7 cases, one case was classified as stage I b1, two stage I b2, one stage IIa, one stage IIb, and one stage IIIb. On the basis of their stages of condition, one subject with stage III b underwent chemotherapy, and one with stage Ib2 received extensive hysterectomy plus pelvic lymphadenectomy, while the other 5 cases were treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy. Of the 7 patients, 4 had relapse-free survival of 14, 14, 16 and 28 months respectively. It is concluded that SCCC is an aggressive tumor with propensity for early pelvis lymph node metastases. Early-stage patients should be treated by extensive hysterectomy and pelvic lymphadenectomy in combination with pre- and/or post-operative adjuvant chemotherapy and radiotherapy.