Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

This paper summarizes Li Fei's academic insights and clinical experience in treating intractable facial paralysis.Li Fei posits that prolonged illness inevitably leads to deficiency and stasis,and thus,the treatment of intractable facial paralysis should first focus on identifying the etiology and syndrome differentiation,resolving stasis and unblocking stagnation,and regulating qi and blood,with particular emphasis on the relaxation of the meridian sinew system.The meridian sinew system,affiliated with the meridian and collateral,serves as the framework through which qi and blood nourish muscles,tendons,and joints,playing a crucial role in facial paralysis treatment.Guided by the theory of the meridian sinew system,Li Fei employs syndrome-based treatment,integrating the anatomy of facial expression muscles.His approach includes needle-knife therapy to release adhesions and break stasis,acupuncture to harmonize qi and blood,and intradermal needle therapy for sustained stimulation.Through these methods,the meridian sinew system is relaxed,qi and blood are regulated,and facial muscles are nourished,leading to gradual recovery from facial paralysis.

Objective To explore the potential characteristics of self-management behavior in maintenance hemodialysis patients with hypertension and determine the influencing factors of different characteristics,so as to provide reference for improving self-management behavior.Methods A total of 192 maintenance hemodialysis patients with hypertension who received dialysis in The First Hospital Affiliated to Naval Medical University from May to September 2022 were enrolled by convenience sampling.A general information questionnaire,hypertension self-management behavior scale,Morisky medication adherence scale-8 items,and medication adherence self-efficacy scale-revision(MASES-R)were used to investigate the potential categories of self-management behavior in maintenance hemodialysis patients with hypertension,and the predictive indicators of each category were analyzed by latent profile analysis.Results Three latent categories of self-management behavior in maintenance hemodialysis patients with hypertension were identified:low self-management behavior,moderate self-management behavior,and high self-management behavior.Medication adherence and medication adherence self-efficacy were predictors of high self-management behavior.Monitoring blood pressure once daily was a predictor of moderate self-management behavior.Conclusion There is significant self-management characteristics among maintenance hemodialysis patients with hypertension.These characteristics and risk factors should be identified early to help patients improving their self-management.

Objective:To explore effect and potential mechanism of disulfiram on necrotizing apoptosis of renal podocytes and macrophages.Methods:Mouse renal podocyte MPC-5 and macrophages J774A.1 and BMDM cells were cultured in vitro and treated with TNF-α,Smac mimetic LCL-161 and pan-caspase inhibitor IDN-6556(TSI)to induce necroptosis.Cell necrosis was detected by propi-dium iodide staining.Western blot was used to detect protein levels of necroptosis markers MLKL,RIPK3 and RIPK1.Immuno-fluorescence microscopy was used to observe the subcellular distribution of RIPK3 and p-MLKL in MPC-5 cells.Results:TSI treat-ment induced significant necroptosis in both MPC-5 cells and macrophages.Disulfiram was able to inhibit necroptosis in these cells in a dose-dependent manner.Moreover,disulfiram markedly blocked the phosphorylation of RIPK1,RIPK3 and MLKL.The aggregation of RIPK3 and p-MLKL were also suppressed by disulfiram.Conclusion:Disulfiram inhibits necroptosis in podocytes and macrophages by suppressing RIPK1/RIPK3/MLKL signaling pathway.

Objective:To explore the relationship between the clinical outcome of emotional symptoms and cognitive performance and related cerebral oxygenated hemoglobin in adolescents with depression.Methods:Through subject recruitment, 46 adolescent patients with depression (patient group) from the First Hospital of Shanxi Medical University were selected as the subjects for this study from December 2020 to December 2021, including 8 males and 38 females, aged 12-18 (15.7±2.3) years old. All patients received sertraline treatment for 8 weeks and were further followed into responders ( n=24) and non-responders ( n=22) according to the outcome of emotional symptoms. In the meantime, 51 healthy controls (control group) were enrolled, including 7 males and 44 females, aged 12-18 (16.1±1.5) years old. The repeatable battery for the assessment of neuropsychological status (RBANS) was conducted to measure the multi-dimensional neurocognitive performance, and the functional near-infrared spectroscopy (fNIRS) was used to assess changes in the concentration of oxyhemoglobin (HBO) during the verbal fluency test. The differences were compared in multi-dimensional cognitive performance and cerebral HBO level between each patient group and control group and between responders and non-responders. The changes were analyzed in cognitive performance and cerebral HBO level after intervention in responders and non-responders. Results:At baseline, compared to the control group, the patient group performed decreased scores of RBANS, immediate memory, speech function, attention, and delayed memory (88.0 (82.8, 100.0) M ( Q1, Q3) vs. 100.0 (90.0, 110.0) scores; 78.0 (73.0, 87.8) vs.85.0 (78.0, 94.0) scores; (84.4±16.1) vs. (95.7±15.7) scores; 106.0 (99.5, 115.0) vs.118.0 (109.0, 128.0) scores; 94.0 (84.5, 99.0) vs.97.0 (91.0, 101.0) scores), and lower HBO levels in 7 channels (all P<0.05). Compared to responders, non-responders showed more severe impairment of visual-spatial and attention performance (103.9±11.0 vs. 94.4±16.7 scores; 112.5±12.1 vs. 98.0±21.2 scores) ( t=2.30 or 2.87; all P<0.05). After treatment, the scores of RBANS and immediate memory improved significantly in responders (98.8±11.2 vs. 93.0±9.7 scores; 95.2±13.8 vs.83.0±14.6 scores) ( t=-3.00 or-4.97; both P<0.05), but the scores of attention and the HBO level of two channels in the prefrontal cortex were still significantly lower than those of the control group (Z=2.27, 3.02 or 3.04; all P<0.05). Besides, there were no significant differences in the scores of immediate memory and the HBO levels of 3 channels in the temporal lobe between the no-responders and the control group (all P>0.05). Conclusion:Immediate memory injure, attention injure and HBO levels of frontal-temporal lobes may be independent of emotional symptoms among adolescents with depression.

Objective:To explore the relationship between the clinical outcome of emotional symptoms and cognitive performance and related cerebral oxygenated hemoglobin in adolescents with depression.Methods:Through subject recruitment, 46 adolescent patients with depression (patient group) from the First Hospital of Shanxi Medical University were selected as the subjects for this study from December 2020 to December 2021, including 8 males and 38 females, aged 12-18 (15.7±2.3) years old. All patients received sertraline treatment for 8 weeks and were further followed into responders ( n=24) and non-responders ( n=22) according to the outcome of emotional symptoms. In the meantime, 51 healthy controls (control group) were enrolled, including 7 males and 44 females, aged 12-18 (16.1±1.5) years old. The repeatable battery for the assessment of neuropsychological status (RBANS) was conducted to measure the multi-dimensional neurocognitive performance, and the functional near-infrared spectroscopy (fNIRS) was used to assess changes in the concentration of oxyhemoglobin (HBO) during the verbal fluency test. The differences were compared in multi-dimensional cognitive performance and cerebral HBO level between each patient group and control group and between responders and non-responders. The changes were analyzed in cognitive performance and cerebral HBO level after intervention in responders and non-responders. Results:At baseline, compared to the control group, the patient group performed decreased scores of RBANS, immediate memory, speech function, attention, and delayed memory (88.0 (82.8, 100.0) M ( Q1, Q3) vs. 100.0 (90.0, 110.0) scores; 78.0 (73.0, 87.8) vs.85.0 (78.0, 94.0) scores; (84.4±16.1) vs. (95.7±15.7) scores; 106.0 (99.5, 115.0) vs.118.0 (109.0, 128.0) scores; 94.0 (84.5, 99.0) vs.97.0 (91.0, 101.0) scores), and lower HBO levels in 7 channels (all P<0.05). Compared to responders, non-responders showed more severe impairment of visual-spatial and attention performance (103.9±11.0 vs. 94.4±16.7 scores; 112.5±12.1 vs. 98.0±21.2 scores) ( t=2.30 or 2.87; all P<0.05). After treatment, the scores of RBANS and immediate memory improved significantly in responders (98.8±11.2 vs. 93.0±9.7 scores; 95.2±13.8 vs.83.0±14.6 scores) ( t=-3.00 or-4.97; both P<0.05), but the scores of attention and the HBO level of two channels in the prefrontal cortex were still significantly lower than those of the control group (Z=2.27, 3.02 or 3.04; all P<0.05). Besides, there were no significant differences in the scores of immediate memory and the HBO levels of 3 channels in the temporal lobe between the no-responders and the control group (all P>0.05). Conclusion:Immediate memory injure, attention injure and HBO levels of frontal-temporal lobes may be independent of emotional symptoms among adolescents with depression.

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

Objective To investigate the influencing factors for low-level viremia (LLV) and their dynamic changes in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogues (NAs) for the first time. Methods A retrospective analysis was performed for 78 CHB patients who attended Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, from November 2020 to March 2022 and received antiviral therapy with NAs for at least 12 months, and according to HBV DNA level during treatment, they were divided into sustained virologic response (SVR) group with 58 patients and LLV group with 20 patients. The independent samples t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the independent influencing factors for LLV and establish a predictive model, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of this model. The Kaplan-Meier method was used to analyze cumulative HBV DNA negative conversion rate, and the Log-rank test was used for comparison. The analysis of variance with repeated measures was used to analyze the differences in HBV DNA and HBsAg between the two groups or within each group at weeks 0, 12, 24, 36, and 48. Results Compare with the SVR group, the LLV group had significantly higher HBeAg positive rate (90.0% vs 48.3%, χ 2 =10.701, P =0.001), log(HBV DNA) value (7.26±1.46 vs 5.65±1.70, t =-4.178, P < 0.001), and log(HBsAg) value (4.53±0.86 vs 3.44±0.93, t =-4.813, P < 0.001) and significantly lower age [29 (26-34) vs 33 (30-43), Z =-2.751, P =0.009], alanine aminotransferase (ALT) [67.0 (54.0-122.0)U/L vs 111.0 (47.0-406.0)U/L, Z =-2.203, P =0.028], aspartate aminotransferase [43.5 (32.8-62.8) U/L vs 77.5 (35.0-213.0)U/L, Z =-2.466, P =0.014], and liver stiffness measurement [7.7 (6.3-8.5)kPa vs 8.9 (7.2-11.4)kPa, Z =-2.022, P =0.043]. The multivariate logistic regression analysis showed that baseline HBV DNA (odds ratio [ OR ]=2.365, 95% confidence interval [ CI ]: 1.220-4.587, P =0.011), HBsAg ( OR =4.229, 95% CI : 1.098-16.287, P =0.036), and ALT ( OR =0.965, 95% CI : 0.937-0.994, P =0.018) were independent influencing factors for LLV in CHB patients, and the predictive model of Logit(MLLV)=-8.668+1.441×lgHBsAg+0.598×lgHBV DNA-0.016×ALT was established based on these factors, which had a larger area under the ROC curve than HBV DNA, HBsAg, and ALT (0.931 vs 0.774/0.856/0.666), with a sensitivity of 85.00% and a specificity of 93.10% at the optimal cut-off value of 0.44. The CHB patients with baseline HBV DNA > 7.29 lgIU/mL or HBsAg > 4.38 lgIU/mL had a significantly lower DNA negative conversion rate than those with DNA ≤7.29 lgIU/mL or HBsAg ≤4.38 lgIU/mL ( χ 2 =22.52 and 26.35, both P < 0.001). In the CHB patients, the highest reduction rates of HBV DNA and HBsAg were observed at weeks 12 and 24, respectively, and the LLV group had significantly higher levels of HBV DNA and HBsAg than the SVR group at weeks 0, 12, 24, 36, and 48 (HBV DNA: t =-4.084, -4.526, -5.688, -7.123, and -6.266, all P < 0.001; HBsAg: t =-4.652, -4.691, -4.952, -4.804, and -4.407, all P < 0.001). Conclusion For the CHB patients treated with NAs for the first time, those with high HBV DNA load, high HBsAg quantification, and low ALT level at baseline are more likely to develop LLV, and dynamic monitoring of these indices is of great significance to observe the onset of LLV.

Objective To investigate the effects of cholesterol-lowering agents on the proliferation, stemness characters, migration, invasion, and neutrophil extracellular traps formation (NETs) formation in liver cancer cells. Methods ASPP2 or HMGCR gene was knocked down in mouse liver cancer cell Hepa1-6 to establish cells with high or low cholesterol, respectively. Simvastatin and berberine were used to reduce cholesterol synthesis. CCK-8 and plate cloning assays were conducted to detect the proliferation ability of liver cancer cells. Sphere formation assay and qRT-PCR were used to analyze the stemness character and expression of related genes. Wound-healing assay and Transwell assay were used to analyze the ability of cell migration and invasion. Immunofluorescence staining was carried out to analyze the effect of lipid-lowering agent on NETs formation. Results Cholesterol-lowering agents significantly inhibited the proliferation and stemness-related gene expression of Hepa1-6 cells (P < 0.001), significantly inhibited the migration and invasion of Hepa1-6 cells (P < 0.001), and significantly inhibited the neutrophil-induced invasion and formation of NETs (P < 0.001). Conclusion Cholesterol-lowering agents suppress the proliferation and invasion via inhibiting the stemness characters and NETs formation in liver cancer cells. It is a potential strategy for the treatment of liver cancer metastasis.

Objective:To study the problems found in the implementation of key clinical specialty programs and come up with feasibility suggestions.Methods:November 2020 to January 2021, by means of quota sampling and snowball sampling, 22 depth interviews were made with principal-investigators, project team elites, leaders of functional departments, and experts of independent examination teams. The interview data were subject to theme analysis.Results:Six(27%) of the interviewees confused the concepts of " key specialty" and " key discipline" ; 9(41%) of them held that at specific stage of the program development, the connotation and implementation emphasis of specialty development and those of key disciplines were overlapped to some extent. Twenty(88%)of them held that functional management process and responsibility should be further refined, 19(86%) said that lack of professional financial knowledge hindered their program implementation, 16(73%) reported difficulties in information statistics, management and sharing, 19(86%)presented disputes in understanding the program examination criteria.Conclusions:In the implementation of key clinical specialty program, management at various levels should work in alignment with program teams, provide accurate definition and guidance to key steps and working mechanisms, refine the management process, provide accurate financial management, and build information platforms for big data collection and sharing.