Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Aim To study the effect of Guben Yanling pills on liver aging in aging mice and the related mech-anism.Methods The mice were randomly divided in-to blank control group,model group,vitamin E group(0.1 g·kg-1)and low,medium and high dose groups(0.59,1.17,2.34 g·kg-1)of Guben Yan-ling pills.The aging mouse model was established by subcutaneous injection of D-galactose(150 mg·kg-1)into the back of neck.At the same time of mod-eling,the corresponding drugs were given by gavage once a day for six weeks.The main organ indexes were calculated.HE staining was used to observe the mor-phology of liver tissue.Colorimetry was used to detect the activity of β-galactosidase in liver.ELISA was used to detect the content of TNF-α,IL-1 β,IL-6,IL-4,IL-10.Western blot was used to detect the protein relative expression level of IKKβ,Iκ Bα,NF-κB p65.Immunofluorescence was used to detect the expression level of NF-κB p65.Results Compared with the blank control group,the organ index of the brain,liv-er,kidney,spleen,and thymus in the model group decreased(P＜0.05,P＜0.01),the activity of β-galactosidase increased(P＜0.01),liver tissue mor-phology and structure were significantly damaged,the content of TNF-α,IL-1 β and IL-6 increased(P＜0.01),the content of IL-4 and IL-10 decreased(P＜0.01),the levels of IKKβ,NF-κB p65 in-creased(P＜0.01),the levels of IKBα decreased(P＜0.01),and the levels of NF-κB p65 in nucleus increased(P＜0.01).Compared with the model group,the organ indexes of brain,liver,kidney,spleen,and thymus in each dose group of Guben Yan-ling pills increased(P＜0.05,P＜0.01),the activity of β-galactosidase decreased(P＜0.01),the morpho-logical and structural damage of liver tissue was signifi-cantly improved,the content of TNF-α,IL-1 β and IL-6 decreased(P＜0.01),the content of IL-4 and IL-10 increased(P＜0.01),the levels of IKKβ,NF-κB p65 decreased(P＜0.01),the levels of IκBα in-creased(P＜0.01),and the levels of NF-κB p65 in nucleus decreased(P＜0.01).Conclusions Guben Yanling pills can antagonize liver aging in mice,and its mechanism may be related to inhibiting the activa-tion of NF-κB signaling pathway in liver,downregulat-ing downstream pro-inflammatory factor levels,upregu-lating anti-inflammatory factor levels,and alleviating inflammation in liver.

Aim To investigate the effect of Celastrol on the expression of Ezrin in tissues and HaCaT cells of DNCB sensitisation-induced atopic dermatitis(AD)mice.Methods BALB/c mice were taken and ran-domly divided into the control,DNCB group,Celastrol 25 μg,50 μg,75 μg treatment group,and Dex group,with 8 mice in each group;HaCaT cells were induced with TNF-α and treated with 1 μmol·L-1 Celastrol and Ezrin siRNA.The thickness of the skin on the ear and back of mice was measured by a thickness gauge,and the spleen and lymph nodes of mice were taken to observe the changes.HE and toluidine blue staining were used to observe the inflammatory cells and mast cell infiltration in mice.Flow cytometry was used to detect the levels of IL-4 and TNF-α in the lymph nodes of mice,and enzyme-linked immunosorbent was used to determine the levels of IL-4,TNF-α and IgE in serum of mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells.Western blot was used to detect the expression of P-Ezrin and Ezrin in skin tissues.Results Celastrol significantly inhibited the swelling of ear and back skin tissues,reduced the de-granulation of inflammatory cells and mast cells,low-ered serum IgE and serum and lymph node levels of IL-4 and TNF-α,and reduced the activation of Ezrin in mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells was restored by the treat-ment with Ezrin siRNA.Conclusion Celastrol amel-iorates AD,which may be achieved by modulating Ezrin activation.

Objective To investigate the correlation between the expression of Toll-like receptor 4(TLR4)and chitosanase 3-like protein 1(CHI3L1)in colon cancer tissue and the prognosis of patients after radical surgery.Methods A total of 152 patients who underwent radical colon cancer surgery in our hospital from January 2017 to May 2018 were collected and divided into the good prognosis group(n=97)and the poor prognosis group(n=47)according to the 5-year survival status after surgery.Immunohistochemical staining was applied to detect the expression levels of TLR4 and CHI3L1 in colon cancer tissues and adjacent tissues;the correlation between the expression of TLR4 and CHI3L1 in colon cancer tissue and the prognosis of patients was analyzed,and the influencing factors for prognosis of colon cancer patients were analyzed.Results The positive expression rates of TLR4 and CHI3L1 in colon cancer tissues were obviously higher than those in adjacent tissues(P<0.05).The expression of TLR4 in colon cancer tissue was related to the degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05),the expression of CHI3L1 was related to the tumor diameter,degree of tumor differentiation,clinical staging,and lymph node metastasis of colon cancer patients(P<0.05).Compared with the good prognosis group,the poor prognosis group had higher proportions of patients with poorly differentiated tumor,clinical stageⅢ,lymph node metastasis,and positive expression of TLR4 and CHI3L1(P<0.05).The 5-year survival rate of patient with TLR4 positive expression was 60.38%,which was lower than that of 86.84% of patients with TLR4 negative expression(χ2=9.104,P<0.05);the 5-year survival rate of patients with CHI3L1 positive expression was 58.06%,which was lower than that of 84.31% of patients with CHI3L1 negative expression(χ2=10.935,P<0.05).The positive expression of TLR4 and CHI3L1,poorly differentiated tumor,clinical stage Ⅲ,and lymph node metastasis were the independent risk factors for the prognosis of colon cancer patients(P<0.05).Conclusion TLR4 and CHI3L1 are related to the occurrence and clinicopathological features of colon cancer,and the positive expression of TLR4 and CHI3L1 in colon cancer tissues is not conducive to the prognosis of patients,so both of them are expected to become clinical treatment targets.