The incidence and mortality of hepatocellular carcinoma (HCC) in China are among the highest in the world, imposing a heavy social burden. Liver resection and liver transplantation are the primary radical treatments for HCC, although most patients are no longer able to meet the surgical requirements at initial diagnosis. Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT) has the advantages of shrinking tumors, enlarging residual liver, regressing portal vein tumor thrombus and improving the quality of life, which can be used for conversion, downstaging and bridging therapy for HCC before surgical treatment, enabling patients regain the chance of radical treatment and reducing the postoperative recurrence rate. This review focuses on the clinical application and progress of ⁹⁰Y-SIRT in this field.

Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Objective:Constructing efficacy evaluation index of TCM in treating kidney-yang deficiency syndrome based on three-dimensional hybrid method.Methods:The outcome index list of kidney-yang deficiency syndrome was preliminarily constructed through literature research, questionnaire survey and expert interview. The core indicators of kidney-yang deficiency syndrome were screened by Delphi questionnaire, and the expert consensus meeting was held to determine the core outcome of kidney-yang deficiency syndrome.Results:The TCM symptoms of kidney-yang deficiency syndrome: 7 items: frequent urination at night, waist pain, low libido, chills, fatigue, diarrhea and mental malaise. Related core indicators of kidney-yang deficiency syndrome: Level quality of life score (scale), sex life level (sexual self satisfaction, sexual life log, etc.)two entries, objective indicators in the core index and stronger correlation disease, curative effect evaluation, can be combined with clinical research involves the related diseases, used to supplement the curative effect, as recommendations, not as the main body of kidney-yang deficiency syndrome curative effect evaluation content.Conclusion:This study refers to the clinical trial of the TCM core outcome to develop technical specifications, in the development process and methods, through the "combination of qualitative and quantitative research methods" "combination of subjective and objective indicators" "combination of doctor-patient evaluation" three dimensions of mixed research methods, formation of kidney-yang deficiency syndrome curative effect evaluation of the core outcome, for the kidney-yang deficiency syndrome curative effect evaluation standard of prophase research foundation, to provide ideas and methods for the evaluation of curative effect of syndrome.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.

Patients with chronic obstructive pulmonary disease have the disease phenomenon of fear of exercise because of dyspnea, which can accelerate the body degradation rate, weaken muscle strength, reverse increase dyspnea, and delay the recovery of the disease. As a result, this article examines the theoretical underpinnings and specific measures of dyspnea belief intervention programs for chronic obstructive pulmonary disease patients at home and abroad, summarizes the limitations of previous studies, and makes pertinent recommendations in an effort to serve as a guide for early patient prevention and the development of scientific and feasible intervention programs.

The mechanistic target of rapamycin(mTOR)plays a pivotal role in various cellular processes,including growth,proliferation and differentiation.As an essential component of the human immune system,T lymphocytes are regulated by mTOR through metabolic pathways such as carbohydrate metabolism and lipid metabolism.This article summarizes the critical role of mTOR in T cell differentiation and reviews recent advances in natural compounds that modulate T cells via mTOR.These findings contribute to the development of mTOR-targeted therapies for diseases.

Objective:To analyze the basic characteristics and change trend of mortality in HIV-infected patients aged ≥60 years in China from 2013 to 2021.Methods:The data of HIV-infected patients aged ≥60 years at diagnosis were collected from China Information System for Disease Control and Prevention to calculate the mortality density. The trajectory model was fitted using the Proc traj process in software SAS 9.4 to explore trajectory of AIDS-related mortality density and non-AIDS-related mortality density under different combinations of region, gender and age.Results:Between 2013 and 2021, a total of 244 770 HIV-infected patients were reported with 40 079 AIDS-related deaths and 50 245 non-AIDS-related deaths. The AIDS-related mortality density was 6.32 per 100 person-years, and the non-AIDS-related mortality density was 7.92 per 100 person-years, both of which showed decreasing trends over the years, and the mortality density in men was higher than that in women. Two developmental trajectories could be categorized for different trends of AIDS-related mortality density: the lower mortality density group accounted for 80.95% and showed a slow decreasing trend; the higher mortality density group accounted for 19.05% and showed a three-curve developmental trend. There were three developmental trajectories of non-AIDS-related mortality density trends: the lower mortality density group accounted for 59.52% and the medium mortality density group accounted for 28.57%, with a flat overall trend in these two groups; the higher mortality density group accounted for 11.91% with a three-curve trend.Conclusions:The mortality in HIV-infected patients aged ≥60 years in China is still high. Further attention should be paid to the early detection, diagnosis and treatment of HIV infection to effectively reduce the density of AIDS-related deaths. At the same time, attention should be paid to non-AIDS-related deaths in the elderly, and comprehensive interventions should be taken. It is necessary to conduct targeted HIV/AIDS prevention and control based on actual situation in different areas and populations

Objective:To investigate the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE+Len+PD-1) versus TACE combined with lenvatinib (TACE+Len) for patients with unresectable intermediate-advanced hepatocellular carcinoma (HCC).Methods:The data of 94 patients with intermediate-advanced HCC who received TACE+Len+PD-1 (One week after TACE, the patient were treated with lenvatinib and PD-1 inhibitor. lenvatinib, 8 or 12 mg/d, orally; PD-1 inhibitor, 200 mg/3 weeks, iv) or TACE+Len (One week after TACE, the patient were treated with lenvatinib.lenvatinib, 8 or 12 mg/d, orally) in the Second Affiliated Hospital of Guangzhou Medical University from June 2019 to February 2021 were collected and retrospectively analyzed. Among these patients, 44 were in the TACE+Len+PD-1 group and 50 were in the TACE+Len group. Tumor responses were evaluated according to modified response evaluation criteria in solid tumors. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were compared between the two groups. The potential prognostic factors for PFS and OS were determined.Results:The ORR of TACE+Len+PD-1 group and TACE+Len group was 72.8% (32/44) and 52.0% (26/50) (χ2=4.25, P=0.039), respectively. The DCR of TACE+Len+PD-1 group and TACE+Len group was 86.4% (38/44) and 62.0% (31/50) (χ2=7.12, P=0.008), respectively. The median PFS and median OS in TACE+Len+PD-1 group were significantly longer than those in TACE+Len group (PFS, 7.9 vs. 5.6 months, χ2=7.91, P=0.005; OS, 18.5 vs. 13.6 months, χ2=4.40, P=0.036). Multivariate Cox regression analyses showed that TACE+Len (HR=2.184,95%CI 1.366-3.493), incomplete tumor capsule (HR=2.002,95%CI 1.294-3.209) and extrahepatic metastasis (HR=1.765,95%CI 1.095-2.844) were the independent risk factors for PFS, while TACE+Len (HR=2.081,95%CI 1.097-3.948) and BCLC stage C (HR=7.325,95%CI 2.260-23.746) were the independent risk factors for OS. The incidence of ≥grade 3 AEs in TACE+Len+PD-1 group was similar to that in TACE+Len group (χ2=0.45, P=0.501). Conclusion:Compared with TACE+Len, TACE+Len+PD-1 resulted in a better tumor response and a longer PFS and OS in patients with intermediate-advanced HCC.