Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

The growth of retroperitoneal liposarcoma is occult, and generally there are no obvious clinical symptoms and signs in the early stage. The clinical and pathological features of primary retroperitoneal liposarcoma are not obvious, which lead to the difficulty of early diagnosis, low surgical resection rate and high postoperative recurrence rate. The effect of radiotherapy and chemotherapy on retroperitoneal liposarcoma is still controversial. In recent years, the researches of genomics and immunohistochemistry have gradually increased, and the related targeted therapies derived from these researches have also shown some preferable results, which provide new ideas for the diagnosis and treatment of retroperitoneal liposarcoma.

Objective To summarize the clinical experience of using 3D planar guide plate combined with bundle diameter technology for extracorporeal pre-fenestration in treating complex thoracoabdominal aortic diseases.Methods The clinical data of 31 patients with complex thoracoabdominal aortic diseases,who were treated with 3D planar guide plate combined with bundle diameter technology of extracorporeal pre-fenestration at the First Affiliated Hospital of Soochow University of China from January 2017 to February 2024,were retrospectively analyzed.The patients' preoperative thin-layer chest and abdominal vascular CTA data were imported into specialized software and to create a 3D planar guide plate.Under the guidance of 3D planar guide plate technology,precise extracorporeal pre-fenestration of aortic covered stent was performed,and combined with bundle diameter technology the endovascular repair of complex thoracoabdominal aortic disease was accomplished.Results Successful operation was accomplished in all patients,and two patients had failed visceral artery reconstruction surgery.The median follow-up time was 55 months,with a technical success rate of 97.6％.The postoperative follow-up blood flow patency rate was 100％,and the phase Ⅰ patency rate of branch arteries was 98％.Three patients experienced internal leakage after surgery,and none of them developed paraplegia or died during the perioperative period.Conclusion In treating complex thoracoabdominal aortic diseases,the use of 3D planar guide plate combined with bundle diameter technology of extracorporeal pre-fenestration is simple,safe and effective,with good short-term therapeutic effect,although its long-term efficacy need to be further investigated.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

The growth of retroperitoneal liposarcoma is occult, and generally there are no obvious clinical symptoms and signs in the early stage. The clinical and pathological features of primary retroperitoneal liposarcoma are not obvious, which lead to the difficulty of early diagnosis, low surgical resection rate and high postoperative recurrence rate. The effect of radiotherapy and chemotherapy on retroperitoneal liposarcoma is still controversial. In recent years, the researches of genomics and immunohistochemistry have gradually increased, and the related targeted therapies derived from these researches have also shown some preferable results, which provide new ideas for the diagnosis and treatment of retroperitoneal liposarcoma.

Objective:To explore the safety of nirmatrelvir/ritonavir (Paxlovid) in the treatment of coronavirus disease 2019 (COVID-19).Methods:Medical records of adult patients with COVID-19 who were hospitalized and treated with Paxlovid in Beijing Ditan Hospital, Capital Medical University between March 23 and May 31, 2022 were collected through the hospital electronic medical record system. The occurrence (time of occurrence, clinical manifestations, severity, etc.) and outcomes of adverse reactions were analyzed retrospectively and the clinical characteristics of patients with or without adverse reactions were compared. Paxlovid was administered orally with nirmatrelvir 300 mg and ritonavir 100 mg every 12 hours for 5 consecutive days.Results:Three hundred and sixty-four patients were entered in the analysis, including 200 males (54.9%) and 164 females (45.1%), with a median age of 60 (19, 92) years. The incidence of adverse reactions of Paxlovid was 13.2% (48/364), and the adverse reactions occurred 1 to 7 days after taking Paxlovid. Among the 48 patients, 37 patients had digestive system symptoms (mainly manifested as diarrhea in 17 patients, bitter mouth in 14 patients, etc.), 7 patients had nervous system symptoms (dizziness in 5 patients, headache in 2 patients), 4 patients had respiratory system symptoms (pharyngalgia in 3 patients, pharyngeal itching in 1 patient), 2 patients had kidney injury, 1 patient had elevated blood uric acid, 1 patient had myalgia, and 1 patient had rash. Of them, 2 patients had digestive and neurological symptoms at the same time, 1 patient had digestive and respiratory symptoms at the same time, and 1 patient had digestive, neurological, and respiratory symptoms at the same time. The severity of adverse reactions was grade 1 in 33 patients (68.8%) and grade 2 in 15 patients (31.2%), and no serious adverse reactions of grade 3 and above occurred. All patients completed 5 days of treatment except 1 patient who discontinued the drug because of intolerance to grade 2 digestive symptoms (nausea and bitter mouth). There were no significant differences in gender, age, body mass index, smoking status, underlying diseases, and COVID-19 clinical classification between the patients with and without adverse reactions (all P>0.05). Conclusions:Paxlovid has a good safety in the treatment of COVID-19. The main adverse reaction is digestive system symptoms, mainly diarrhea and bitter mouth. Most of the symptoms are mild and the patient′s tolerance is good.

Objective:To explore the safety of nirmatrelvir/ritonavir (Paxlovid) in the treatment of coronavirus disease 2019 (COVID-19).Methods:Medical records of adult patients with COVID-19 who were hospitalized and treated with Paxlovid in Beijing Ditan Hospital, Capital Medical University between March 23 and May 31, 2022 were collected through the hospital electronic medical record system. The occurrence (time of occurrence, clinical manifestations, severity, etc.) and outcomes of adverse reactions were analyzed retrospectively and the clinical characteristics of patients with or without adverse reactions were compared. Paxlovid was administered orally with nirmatrelvir 300 mg and ritonavir 100 mg every 12 hours for 5 consecutive days.Results:Three hundred and sixty-four patients were entered in the analysis, including 200 males (54.9%) and 164 females (45.1%), with a median age of 60 (19, 92) years. The incidence of adverse reactions of Paxlovid was 13.2% (48/364), and the adverse reactions occurred 1 to 7 days after taking Paxlovid. Among the 48 patients, 37 patients had digestive system symptoms (mainly manifested as diarrhea in 17 patients, bitter mouth in 14 patients, etc.), 7 patients had nervous system symptoms (dizziness in 5 patients, headache in 2 patients), 4 patients had respiratory system symptoms (pharyngalgia in 3 patients, pharyngeal itching in 1 patient), 2 patients had kidney injury, 1 patient had elevated blood uric acid, 1 patient had myalgia, and 1 patient had rash. Of them, 2 patients had digestive and neurological symptoms at the same time, 1 patient had digestive and respiratory symptoms at the same time, and 1 patient had digestive, neurological, and respiratory symptoms at the same time. The severity of adverse reactions was grade 1 in 33 patients (68.8%) and grade 2 in 15 patients (31.2%), and no serious adverse reactions of grade 3 and above occurred. All patients completed 5 days of treatment except 1 patient who discontinued the drug because of intolerance to grade 2 digestive symptoms (nausea and bitter mouth). There were no significant differences in gender, age, body mass index, smoking status, underlying diseases, and COVID-19 clinical classification between the patients with and without adverse reactions (all P>0.05). Conclusions:Paxlovid has a good safety in the treatment of COVID-19. The main adverse reaction is digestive system symptoms, mainly diarrhea and bitter mouth. Most of the symptoms are mild and the patient′s tolerance is good.

Objective:To analyze the epidemic characteristics of human brucellosis in Xianyang City, Shaanxi Province, to grasp the epidemic trend and provide scientific basis for further prevention and control of human brucellosis.Methods:Descriptive epidemiological methods were used to statistically analyze the incidence data and epidemic data of human brucellosis in Xianyang City, Shaanxi Province from 2011 to 2020 in the "Infectious Disease Surveillance System of China Disease Control and Prevention Information System".Results:A total of 864 human brucellosis cases had been reported in Xianyang City from 2011 to 2020, and there was no dead case. The annual incidence began to increase rapidly from 2014, the highest annual incidence in 2019 was 5.79/10 5. There were statistical differences between the incidence of different years (χ 2 = 900.40, P < 0.001). Human brucellosis cases in Xianyang City were mainly concentrated in dairy goat breeding counties, with a total of 571 cases reported, accounting for 66.09%. Cases were reported in all months of the year, and the peak incidence of human brucellosis was from April to August, accounting for 64.35% (556/864). The age of cases was mainly concentrated in the 40 - 69 years old group, accounting for 68.29% (590/864); the ratio of male to female was 2.40 ∶ 1.00 (610 ∶ 254). The occupation was mainly farmers, accounting for 83.45% (721/864). There had been an increase in the proportion of scattered children, students and preschool children. The total serological positive rate was 3.14% (283/9 009) in Xianyang City, and pathogenic culture showed variant strains. The median of interval between onset time and diagnosis time was 8 days. Conclusion:The prevalence of human brucellosis in Xianyang City, Shaanxi Province shows an overall upward trend, which needs to be paid more attention to and control efforts should be strengthened.

Objective To investigate the efficacy and safety of percutanous transhepatic intrahepatic portosystemic shunt(PTIPS)for chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension.Methods The clinical and imaging data of 38 patients with chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension, who received PTIPS in our hospital from November 2009 to June 2016,were analyzed retrospectively.The differences of the portosystemic pressure gradient(PPG)measured before and after PTIPS procedure was analyzed by a paired samples t-test. All the patients were followed up and the curative effect and operation-correlated complications were observed.Results The PTIPS procedure was technically successful in 36 patients.The other two patients with unsuccessful PTIPS underwent medical treatment,and one of them died of recurrent variceal bleeding 25 months later. Effective portal decompression and free antegrade shunt flow were achieved in 36 patients with successful PTIPS.And the mean PPG was decreased from(25.2±2.9)to(13.2± 1.3) mmHg (1 mmHg=0.133 kPa) before and after PTIPS respectively and the difference was statistically significant(P<0.05).During the procedure,arterial hemorrhage occurred in two patients who subsequently underwent embolization. Biliary injury occurred in one case and percutanous transhepatic biliary drainage (PTBD)was then performed.The mean follow-up period of the 36 patients was(26.7±10.4)months(range from 3.0 to 74.0 months).Hepatic encephalopathy appeared in 4 cases,among which,3 patients recovered after receiving medical treatment, while 1 patient experienced Grade 3 hepatic encephalopathy and recovered after implanting a smaller cover-stent.Shunt dysfunction occurred in 10 cases,of which 8 cases recovered after shunt revision with stent implantation or ballon angioplasty, while 2 cases underwent anticoagulation by warfarin only. During follow-up period, 7 patients died of liver failure(n=4), hepatic cellular carcinoma(n=1), recurrent varicose vein bleeding(n=1), and renal failure(n=1). The other patients remained asymptomatic and shunt patency. Conclusions PTIPS is both safe and effective for the treatment of symptomatic portal hypertension caused by chronic portal vein occlusion and cavernous transformation.The technical success rate is high,and the short-term curative effect is satisfied.