REVIEW | doi:10.20944/preprints202308.2062.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: diabetic kidney disease; proteinuria; pathophysiological mechanism; drug therapy
Online: 31 August 2023 (03:22:20 CEST)
Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate (GFR) decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists (MRAs), and endothelin receptor antagonists (REAs), have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease (T2DKD), providing a new perspective on the clinical diagnosis and treatment of DKD.
ARTICLE | doi:10.20944/preprints202005.0478.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: advanced lung cancer; network-meta analysis; combination therapy; chemotherapy
Online: 31 May 2020 (16:11:51 CEST)
Background: At present, the treatments for patients with advanced lung cancer focus on chemotherapy, targeted therapy, immunotherapy, or a combination of multiple treatments. Purpose: The main purpose of this study is to compare the various chemotherapy-based combination therapies and find the best one for patients with advanced lung cancer. Methods: Based on database (PubMed, EMBASE and Medline) for randomized controlled trials of advanced lung cancer with combination therapy from 2008 to 2020, we searched literatures with overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse as outcome indicators and established a Bayesian mesh meta-analysis for multiple treatment strategies. Then, we combined the results of four outcome indicators to find out the best chemotherapy-based combination therapy strategy for patients with advanced lung cancer, further, we tried to screen out the best drugs of which were commonly used now. Results: It contained a total of 51 studies, including five combination therapies: Chemotherapy/Chemotherapy plus placebo (CT), chemotherapy plus one targeted therapy drug (CT+T), chemotherapy plus two targeted therapy drugs (CT+T+T), chemotherapy combined with immunotherapy (CT+I) or chemotherapy combined with biotherapy (CT+B). In terms of four outcome indicators, CT+I showed the best therapeutic benefits. In the comparison of immunotherapy drugs, pembrolizumab showed the best effect. Conclusion: Our results showed that, among the multiple chemotherapy-based combination therapy strategies, chemotherapy combined with immunotherapy is the best choice for patients with advanced lung cancer, and pembrolizumab combined with chemotherapy has the best effect.
CASE REPORT | doi:10.20944/preprints202005.0103.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: lung adenocarcinoma; papillary thyroid carcinoma; mediastinal lymph nodes; lymphadenectomy
Online: 7 May 2020 (02:30:36 CEST)
In the surgical treatment of lung cancer, systemic mediastinal lymph node dissection, as one important routine procedure, has been accepted by most peers in the world. However, due to the special location of some mediastinal lymph nodes, the difficulty of dissection, and the negative preoperative CT results, the specific scope of lymph node dissection is still controversial. Especially the second group, which is located at the top of thorax, is likely to be overlooked for the above reasons. Here, we report a case of lung adenocarcinoma in which the preoperative CT showed no abnormal lymph nodes in the second group and also no enlarged lymph nodes of the second group were found during the surgery, yet lymphadenectomy was still performed according the routine with the lymph node of station 2 being sampled. In the postoperative pathological report, cancer cells were found in the second group, instead of lung adenocarcinoma, these cells come from thyroid and were proved to be papillary thyroid carcinoma, which is unusual because no obvious indication of thyroid carcinoma was found in preoperative color doppler ultrasound of superficial lymph nodes.
ARTICLE | doi:10.20944/preprints202304.1053.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: 2,5-diketopiperazine derivative; intermolecular bond; liposolubility; electron property; anticancer
Online: 27 April 2023 (07:11:44 CEST)
Based on the marine natural products piperafizine B, X334 and our previously reported compound 4m, fourteen novel 3,6-diunsaturated 2,5-diketopiperazine (2,5-DPK) derivatives (1-2, 4-6, 8-16), together with two known ones (3 and 7), were designed and synthesized as anticancer agents against cell lines A549 and Hela. The MTT assay results showed that the derivatives 6, 8-12 and 15 had moderate to good anticancer capacities with the IC50 values ranging from 0.7 to 8.9 μM. Among them, compound 11 with naphthalen-1-ylmethylene and 2-methoxybenzylidene functions at the 3- and 6-positions of 2,5-DPK ring, respectively, displayed good inhibitory activities to both cancer cells A549 (IC50 = 1.2 μM) and Hela (IC50 = 0.7 μM). It could also induce apoptosis and obviously block the cell cycle progression at G2/M phase in both cells at 1.0 μM. The electron withdrawing functions might not be favorable for the derivatives with high anticancer activities. Additionally, compared to piperafizine B and X334, these semi-N-alkylated derivatives have high liposolubilities (> 1.0 mg•mL-1). Compound 11 can be further developed aiming to the discovery of novel anticancer candidate.
CASE REPORT | doi:10.20944/preprints202005.0079.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Esophageal cancer; Residual stomach; Colon polyps; Jejunum
Online: 5 May 2020 (12:14:41 CEST)
Herein, we reported a case of complete excision of the jejunum for the treatment of esophageal cancer. A 62-year-old male was admitted with complaints of “difficulty in eating for one month and chest pain for 10 days". For complete gastrectomy and colonic polyposis, we chose the jejunum. We completely excised the jejunum and its vessels, anastomosed to the esophageal tumor resection, with no significant complications. This case showed that complete excision of the jejunum with bowel and vessels is an alternative surgical method for the treatment of esophageal cancer with free bowel shortage and no torsion of blood vessels.
ARTICLE | doi:10.20944/preprints202004.0441.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Corona Virus Disease 2019; pulmonary vesicle; prognosis; surgical treatment
Online: 24 April 2020 (12:06:33 CEST)
Background: The Corona Virus Disease 2019 (COVID-19) is spreading globally now. However, the clinical presentation that predict prognosis of the patients are still largely unknow. Methods: We enrolled 393 patients infected with COVID-19 and 30 patients with common pulmonary bulla and reviewed their clinical features to evaluate the potential prognostic value of pulmonary vesicles, especially in the patients with severe symptoms. One COVID-19 patient with vesicles was treated by bullectomy for last resort, and its characteristics of the patient’s perioperative laboratory tests was analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. Results: Patients infected with COVID-19 showed more dependence on ventilator, occurrence of super resistant bacteria, and prone to vesicle formation than common bulla (p<0.05). Disease severity is associated with age, sex, and usage of ventilator, ECMO and antibiotics, super resistance bacteria and vesicle formation (p<0.05). The average mortality rate of COVID-19 patients was 4.10% (25.4% in severe patients, 0.00% in mild patients). Interestingly, the mortality rate further increased in severe patients with pulmonary vesicles than those without pulmonary vesicles (35.7% vs 22.4%, p=0.0442). One COVID-19 patient with vesicles underwent bullectomy and had a poor prognosis, who showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. Conclusions: Patients infected with COVID-19 are more prone to form pulmonary vesicles showed on chest CT scans, as an important poor prognosis factor, especially in the severe patients.
ARTICLE | doi:10.20944/preprints202005.0077.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: centromere protein F (CENPF); Estrogen Receptor beta; Lung Adenocarcinoma (LUAD); WGCNA package; non-small cell lung cancer (NSCLC)
Online: 5 May 2020 (12:08:59 CEST)
The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.