This article reviews the application and future prospects of complement component 5 (C5) inhibitors in kidney transplantation for sensitized recipients. Kidney transplantation significantly improves the survival and quality of life for patients with end-stage kidney disease. However, donor kidney shortages and human leukocyte antigen (HLA) sensitization are major obstacles. HLA-sensitized candidates, particularly highly sensitized ones, face a significantly elevated risk of post-transplant rejection due to pre-existing HLA antibodies. Eculizumab, a terminal complement inhibitor, inhibits rejection by preventing the cleavage of C5 into C5a and C5b, thus blocking the formation of the membrane attack complex and suppressing complement-dependent cytotoxicity.

Objective:To explore the efficacy of interventional therapy for transplant renal artery stenosis (TRAS) and the 1-, 2-, and 3-year survival rates of recipients after treatment.Methods:This is a retrospective case series study. Forty TRAS recipients who underwent interventional treatment at Zhengzhou University People's Hospital between April 2016 and April 2021 were included as the study group. The Kaplan-Meier method was used to calculate the survival rates of the transplanted kidneys and recipients, and survival curves were plotted. The improvement in graft function and blood pressure after interventional therapy in the study group was further analyzed.Results:The 1- and 3-year graft survival rates in the study group after interventional therapy were 87.5% and 82.5%, respectively; the 1-, 2-, and 3-year recipient survival rates were all 100%. One month after interventional therapy, the peak systolic velocity (PSV) and resistance index (RI) of the transplanted kidneys were (235.4±135.1) cm/s and 0.60±0.07, respectively, which were significantly different from the pre-treatment values [(482.8±180.6) cm/s and 0.52±0.12, respectively; both P<0.001]. Serum creatinine levels at 1, 2, and 3 years after interventional therapy were (166.6±93.7) μmol/L, (137.4±57.2) μmol/L, and (137.4±57.9) μmol/L, respectively, all significantly lower than the pre-treatment level [(242.9±156.8) μmol/L; P=0.001, P<0.001, and P<0.001, respectively]. Systolic blood pressure at 1, 2, and 3 years after treatment was (138.5±11.1) mmHg (1 mmHg=0.133 kPa), (134.0±12.0) mmHg, and (130.8±10.8) mmHg, respectively, all significantly lower than the pre-treatment value [(153.8±9.8) mmHg; all P<0.001]. Diastolic blood pressure at 1, 2, and 3 years after treatment was (84.4±9.9) mmHg, (83.7±10.1) mmHg, and (81.9±6.9) mmHg, respectively, all significantly lower than the pre-treatment value [(93.5±12.8) mmHg; P=0.002, P=0.001, and P<0.001, respectively]. Conclusions:Interventional therapy can enable the majority of kidney transplant recipients diagnosed with TRAS to avoid the need for further dialysis, and it has positive effects on both transplant renal function and blood pressure control.

In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural-cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.
Humans ; Neoplasms/metabolism* ; Receptors, Neurotransmitter/physiology* ; Animals ; Tumor Microenvironment/physiology*

This article reviews the application and future prospects of complement component 5 (C5) inhibitors in kidney transplantation for sensitized recipients. Kidney transplantation significantly improves the survival and quality of life for patients with end-stage kidney disease. However, donor kidney shortages and human leukocyte antigen (HLA) sensitization are major obstacles. HLA-sensitized candidates, particularly highly sensitized ones, face a significantly elevated risk of post-transplant rejection due to pre-existing HLA antibodies. Eculizumab, a terminal complement inhibitor, inhibits rejection by preventing the cleavage of C5 into C5a and C5b, thus blocking the formation of the membrane attack complex and suppressing complement-dependent cytotoxicity.

Objective:To explore the efficacy of interventional therapy for transplant renal artery stenosis (TRAS) and the 1-, 2-, and 3-year survival rates of recipients after treatment.Methods:This is a retrospective case series study. Forty TRAS recipients who underwent interventional treatment at Zhengzhou University People's Hospital between April 2016 and April 2021 were included as the study group. The Kaplan-Meier method was used to calculate the survival rates of the transplanted kidneys and recipients, and survival curves were plotted. The improvement in graft function and blood pressure after interventional therapy in the study group was further analyzed.Results:The 1- and 3-year graft survival rates in the study group after interventional therapy were 87.5% and 82.5%, respectively; the 1-, 2-, and 3-year recipient survival rates were all 100%. One month after interventional therapy, the peak systolic velocity (PSV) and resistance index (RI) of the transplanted kidneys were (235.4±135.1) cm/s and 0.60±0.07, respectively, which were significantly different from the pre-treatment values [(482.8±180.6) cm/s and 0.52±0.12, respectively; both P<0.001]. Serum creatinine levels at 1, 2, and 3 years after interventional therapy were (166.6±93.7) μmol/L, (137.4±57.2) μmol/L, and (137.4±57.9) μmol/L, respectively, all significantly lower than the pre-treatment level [(242.9±156.8) μmol/L; P=0.001, P<0.001, and P<0.001, respectively]. Systolic blood pressure at 1, 2, and 3 years after treatment was (138.5±11.1) mmHg (1 mmHg=0.133 kPa), (134.0±12.0) mmHg, and (130.8±10.8) mmHg, respectively, all significantly lower than the pre-treatment value [(153.8±9.8) mmHg; all P<0.001]. Diastolic blood pressure at 1, 2, and 3 years after treatment was (84.4±9.9) mmHg, (83.7±10.1) mmHg, and (81.9±6.9) mmHg, respectively, all significantly lower than the pre-treatment value [(93.5±12.8) mmHg; P=0.002, P=0.001, and P<0.001, respectively]. Conclusions:Interventional therapy can enable the majority of kidney transplant recipients diagnosed with TRAS to avoid the need for further dialysis, and it has positive effects on both transplant renal function and blood pressure control.

BACKGROUND:Exercise is an effective method for preventing and treating osteoporosis,but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE:To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats,and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS:A rat model of postmenopausal osteoporosis was established,and a 24-week moderate-intensity exercise was used for intervention.After the experiment,serum estradiol levels were measured by ELISA,and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT.The biomechanical indicators of the tibia were tested by a three-point bending test.Autophagosomes were observed by transmission electron microscopy.The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION:The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group(P＜0.01).The body mass of rats in each group increased,and the order was the ovariectomized group＞the ovariectomized+exercise group＞the sham-operation group＞the sham-operation+exercise group.The bone mineral density and bone mass of rats in all groups significantly increased(P＜0.01),but the increase in the ovariectomized group was significantly lower than that of the other groups,and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group.Compared with the sham-operation group,the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased(P＜0.01),while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased(P＜0.01).Compared with the ovariectomized+exercise group,the ovariectomized group showed significantly lower bone volume fraction,number of trabeculae,and bone mineral density of cancellous bone(P＜0.05),extremely significantly lower trabecular thickness(P＜0.01),and significantly higher mean trabecular pattern factor,trabecular separation,and structural model index(P＜0.01).Compared with the ovariectomized group,the LC3-Ⅱ/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group(P＜0.05).Compared with the sham-operation and ovariectomized groups,the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups,respectively.To conclude,moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels.

Objective:To analyze the differentially expressed genes in PBMCs of patients with systemic lupus erythematosus (SLE) by bioinformatics methods screening and analyzing the key genes related to ferroptosis, and explore the possible mechanism of ferroptosis involved in the pathogenesis of SLE at the transcription level.Methods:The data sets and samples of healthy people (HC) and SLE patients who met the screening criteria were retrieved from the Gene Expression Omnibus (GEO), a sub-database of the National Center for Biotechnology Information (NCBI). The differentially expressed genes, GO enrichment analysis and KEGG pathway enrichment analysis were analyzed by GEO2R, R language and related software packages. The protein interaction network (PPI) of differential genes was analyzed by STRING, Cytoscape and other tools to explore the key genes and pathways. In addition, real-time quantitative reverse transcription PCR (RT-qPCR) was used to verify the expression of key genes. Mann-Whitney U test was used to compare the expression of key genes in PBMCs between the two groups. Spearman rank correlation analysis was used to explore the relationship between SLE disease activity and the level of key genes. Results:Six data sets were included in this study. A total of 166 genes related to ferroptosis were differentially expressed between SLE and HC groups. The differential genes were specifically expressed in alveolar macrophages, neutrophils, CD49 + cells and CD31 + cells. GO enrichment analysis and KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly involved in multiple signaling pathways closely related to SLE, such as oxidative stress response, infection and TNF signaling pathway. Hub genes screened by different algorithms all suggested RELA as a key gene, and RT-qPCR confirmed that compared with the RELA gene expression level in the HC group [0.75(0.37,1.13)], the expression level in SLE group [2.02 (1.19,4.06)] was increased, the difference was statistically significant ( Z=-3.08, P=0.002), and was positively correlated with the corresponding SLEDAI score of SLE samples ( r=0.52, P=0.019). Conclusion:The ferroptosis of many immune cells, including alveolar macrophages and CD49 + NK cells, is involved in the pathogenesis of SLE. RELA may be involved in the ferroptosis of PBMCs in SLE through the NF-κB pathway.

Objective To evaluate the prognostic value of radiation-induced lymphocytopenia in the survival of patients with primary hepatocellular carcinoma receiving radiation therapy. Methods The clinical data of 98 patients with unresectable primary hepatocellular carcinoma who received radiotherapy were retrospectively analyzed. The minimum absolute lymphocyte count (min ALC) was graded in accordance with CTCAE V4.0. The optimal threshold of min ALC for prognosis was calculated by using the receiver operating characteristic curve, and the correlation of min ALC with clinical characteristics and dosimetry parameters was analyzed. The Kaplan-Meier method was employed to analyze the survival of patients with different levels of min ALC. Univariate and multivariate Cox proportional regression models were applied to analyze prognostic factors. Results The baseline and min ALC of 98 patients during radiotherapy were 1.52×10⁹/L and 0.45×10⁹/L, respectively(P<0.001). The optimal cut-off value of min ALC for the prediction of the one-year survival rate was 0.38×10⁹/L. GTV, the mean dose of the liver and spleen, the V5 and V10 of the liver and spleen, and the V15 of the spleen were correlated with min ALC, and the V5 of the liver was an independent predictor of min ALC. The overall survival of patients with high min ALC was higher than that of patients with low min ALC. Independent prognostic factors were min ALC≤0.38×10⁹/L (HR=0.515, P=0.024), min ALC≥grade 3 (HR=0.576, P=0.032), tumor thrombus in the portal/vena cava, Child-Pugh grade A, increase of ≥2 points in the Child-Pugh score after radiotherapy, and received more than two other therapies. Conclusion Min ALC≤0.38×10⁹/L and min ALC≥grade 3 have independent prognostic value in patients with unresectable hepatocellular carcinoma receiving radiotherapy.

Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.

Objective To evaluate the short-term efficacy and quality of life of primary hepatocellular carcinoma patients after radiotherapy and pregabalin treatment for neuropathic pain with bone metastasis. Methods 32 patients with primary hepatocellular carcinoma bone metastases were treated with radiotherapy combined with pregabalin treatment.Then, we prospectively studied the analgesic efficacy for neuropathic pain and quality of life, used the brief pain inventory and douleur neuropathique 4 questionnaire (DN4) to evaluate pain at baseline, one and two months after radiotherapy, assessed pain response using the international consensus endpoint definition of bone metastasis, and used European Organization for Research and Treatment of Cancer Research and Treatment Quality of Life Questionnaire (EORTC QLQ-C30) and bone metastasis module (QLQ-BM22) for quality of life assessment. Results One and two months after radiotherapy, the average DN4 score of neuropathic pain decreased, and the objective pain relief rates were 62.8% and 68.6%, respectively.The physical, emotional, social, and role functional scores of EORTC QLQ-C30 functional scale significantly increased in the first month after radiotherapy.Symptom scale of pain (P=0.015), insomnia (P=0.035), and loss of appetite (P=0.022) improved, and fatigue was aggravated (P < 0.05).Two months after radiotherapy, the mean overall health score and all functional scale scores significantly increased than those at baseline.The scores of all symptom scales decreased, except fatigue, constipation, and financial difficulties (P < 0.05).In addition, pain responders showed significant improvement in emotional function (P=0.025) and physical function (P=0.029) in the functional scale and in pain (P=0.014) and fatigue (P=0.035) in the symptom scale.The QLQ-BM22 score showed that the painful sites (P=0.021) and pain characteristics (P=0.04) of the responders significantly improved compared with those of nonresponders two months after radiotherapy. Conclusion Radiotherapy combined with pregabalin can relieve neuropathic pain caused by bone metastasis from primary hepatocellular carcinoma and greatly improve the quality of life, particularly in pain responders.