The pathogenic role of succinate-SUCNR1: a critical function that induces renal fibrosis via M2 macrophage.

BACKGROUND: Renal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis. METHODS: Male C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms. RESULTS: Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3ß/ß-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells. CONCLUSIONS: The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3ß/ß-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1.

Effect of Compound Danshen Injection Combined with Magnesium Sulfate on Oxidative Stress, TNF-α, NO, and Therapeutic Efficacy in Severe Preeclampsia.

Aims: This study is designed to explore the effect of compound Danshen injection combined with magnesium sulfate on TNF-α, NO, oxidative stress, and therapeutic efficacy in severe preeclampsia (S-PE). Methods: Sixty S-PE patients were placed into the control group and the therapy group, randomly. The control group was under the treatment of magnesium sulfate, and the therapy group was under the treatment of compound Danshen injection with magnesium sulfate. After treatment, the therapeutic efficacy of the two groups was comparatively analyzed. Results: 7 days after treatment, DBP, SBP, and 24 h urinary protein were sharply lower than those before treatment. The 24 h urinary protein was notably lower in the therapy group. After treatment, the expression level of TNF-α in both groups was notably higher than before treatment, while NO level was higher than that before treatment. Furthermore, D-D level in two groups was dramatically decreased compared to that before treatment. Moreover, Fib, PT, and APTT in two groups showed statistically significant differences after 7 days. The contents of ALT, AST, BUN, and Scr in therapy group were notably lower than those in control group. Conclusion: Our results indicated that compound Danshen injection could improve renal function, blood hypercoagulability, and oxidative stress level and had a better therapeutic effect on S-PE.

Effects of Traditional Chinese Medicine Anticancer Decoction Combined with Basic Chemotherapy and Nursing Intervention on Oral Cancer Patients after Surgery and Its Effect on Tumor Markers and Immune Function.

Objective: To prospectively study the application effect of traditional Chinese medicine (TCM) anticancer decoction with basic chemotherapy and nursing intervention on oral cancer patients after surgery and the effect on tumor markers and immune function. Methods: Eighty-four postoperative oral cancer patients in our hospital from May 2017 to February 2019 were selected and divided into observation group (42 cases) and control group (42 cases). The control group was treated with basic chemotherapy combined with basic nursing care, and the observation group was treated with TCM anticancer decoction and comprehensive nursing intervention on the basis of the control group. The clinical efficacy, the occurrence of adverse reactions, the satisfaction of nursing care, and the two-year cumulative survival rate of the two groups were compared. The immune function, tumor marker level, VAS score, QoR40 score, and survival quality score of the two groups were compared before and after nursing care. Results: The total clinical treatment efficiency of the observation group (88.10%) was significantly higher than that of the control group (69.05%), and the differences between the two groups in oral cleanliness, aspiration frequency, and oral comfort were statistically significant (P < 0.05). The differences in the occurrence of halitosis, oral fungal infection, leukopenia, gastrointestinal reaction, and fever in the observation group were statistically significant compared with the control group (P < 0.05). The nursing satisfaction rate in the observation group (95.24%) was significantly higher than that in the control group (78.57%). The two-year cumulative survival rate of the observation group (92.86%) was significantly higher than that of the control group (73.81%). After nursing care, CD4+, CD4+/CD8+, VAS scores, QoR40 scores, and quality of survival scores in both groups all increased, and CD8+, CD56+, CEA level, NSE level, and CA19-9 level all decreased (all P < 0.05). Conclusion: The clinical efficacy of TCM anticancer decoction with basic chemotherapy and nursing interventions in the treatment of postoperative oral cancer patients was remarkable, which could significantly improve patients' oral cleanliness and comfort, reduce the frequency of sputum aspiration, improve patients' immunity, reduce tumor marker levels, inhibit tumor activity, improve patients' nursing satisfaction, further improve patients' treatment compliance, reduce patients' pain level, improve patients' survival quality, and prolong patients' survival time with high safety. It could be used as a theoretical basis for subsequent clinical research.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

Efficacy of Lycium barbarum L. on plasma lipid concentration in adults: A protocol for systematic review and meta-analysis.

BACKGROUND: Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease. Lycium barbarum L. are widely used as medicinal and functional food and may be particularly beneficial for patients with dyslipidemia. This systematic review protocol is designed to be used to evaluate the effects of Lycium barbarum L. on plasma lipid concentration through systematic reviews and meta-analysis. METHODS: The Following electronic databases will be searched from inception to October 2021: the China National Knowledge Infrastructure, PubMed, Cochrane Library, Web of Science, and Wan-fang database. All randomized controlled trial designs evaluated the effects of Lycium barbarum L. on plasma concentrations of lipids will be included. Two researchers will operate literature retrieval, screening, information extraction, quality assessment, and data analysis independently. The analysis will be conducted using Rstudio software (Version 1.4.1717). RESULTS: The findings will be submitted to a peer-reviewed publication. CONCLUSION: This study will provide practical and targeted evidence in investigating the impact of Lycium barbarum L. on plasma lipid concentration in adults. REGISTRATION NUMBER: INPLASY2021110043.

Synergic highly effective photothermal-chemotherapy with platinum prodrug linked melanin-like nanoparticles.

Cisplatin is widely used in cancer treatment, but the application is limited due to toxicities and its acquired resistance. In this study, we delivered cisplatin to prostate cancer cells by linking the platinum prodrug Pt(IV) to melanin-like nanoparticles (MeNPs), a promising photothermal therapeutic agent with excellent biocompatibility. As expected, the Pt(IV)-MeNPs exhibited brilliant synergic photothermal-chemotherapy upon near-infrared reflection exposure. Compared with free cisplatin, Pt(IV)-MeNPs displayed highly effective antitumour activity both in vitro and in vivo.

Highly effective photothermal chemotherapy with pH-responsive polymer-coated drug-loaded melanin-like nanoparticles.

Dopamine is a neurotransmitter commonly used in clinical treatment. Polydopamine (PDA) has excellent histocompatibility and biosafety and can efficiently convert near-infrared reflection (NIR) to thermal energy. In this study, PDA was used as a promising carrier, and pH-responsive polymer-coated drug-loaded PDA nanoparticles (NPs; doxorubicin@ poly(allylamine)-citraconic anhydride [Dox@PAH-cit]/PDA NPs) were developed. As expected, the Dox@PAH-cit/PDA NPs exhibited excellent photothermal efficiency. In addition, at a low pH condition, the loaded Dox was released from the NPs due to the amide hydrolysis of PAH-cit. Upon NIR exposure (808 nm), the temperature of the NP solution rapidly increases to kill tumor cells. Compared with unbound chemotherapy drugs, the NPs have a stronger cell uptake ability. In vivo, the PDA NPs were able to efficiently accumulate at the tumor location. After intravenous administration and NIR exposure, tumor growth was significantly inhibited. In summary, the present investigation demonstrated that the Dox@PAH-cit/PDA NPs presented highly effective photothermal chemotherapy for prostate cancer.

Comparisons of Surgery and/or Chemotherapy in the Treatment of Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma.

BACKGROUND/AIMS: To investigate the clinical features, imaging characteristics, treatment, and prognosis of primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: We retrospectively analysed the clinical, imaging, and follow-up data of 13 patients (median age, 59 years; range, 21-67 years) with primary pulmonary MALT lymphoma. RESULTS: The main clinical manifestations were chest discomfort (six patients), cough (two), fever (two), chest pain (one), and no obvious symptoms (two). Six patients underwent surgery; three had postoperative chemotherapy; four had chemotherapy alone; and three only had symptomatic and supportive treatment. The follow-up duration was one to 11 years, with one patient lost to follow-up. Two patients died (two years and 11 years post-diagnosis). As of this report, the remaining 10 patients were alive with no disease progression. CONCLUSIONS: Pulmonary MALT lymphoma has atypical clinical manifestations and non-specific imaging changes, and the diagnosis depends on a pathological examination. For patients with confined lesions for which conventional biopsy cannot be performed, surgical excision plays an important role in clarifying the diagnosis and obtaining good therapeutic results and a good prognosis.