[Construction of clinical efficacy evaluation system based on optimal clinical experience].

Evidence-based medicine plays an important role in promoting the scientific nature of clinical decision-making. Howe-ver, there is a problem where evidence derived from clinical research may not necessarily be applicable to individual patients. Evidence-based medicine has been introduced into the field of traditional Chinese medicine(TCM) for over 20 years, and although certain achievements have been made, the overall level of clinical research evidence based on the principles of evidence-based medicine in TCM is not high. The acceptance of TCM diagnosis and treatment guidelines developed based on evidence-based medicine methods is generally low. As revealed by the analysis of the problems in the application of evidence-based medicine in the field of TCM, it is found that there is a structural contradiction between clinical randomized controlled trial(RCT) of TCM and the characteristics of TCM clinical practice. They cannot comprehensively, objectively, and truthfully reflect the clinical efficacy and safety of TCM. Conducting clinical RCTs of TCM in pursuit of "evidence" actually means giving up the advantages of TCM in clinical treatment based on syndrome differentiation, prescription changes along with syndromes, and treatment in accordance with three categories of disease cause, which leads to sacrificing some clinical effectiveness of TCM. Based on the concept of evidence-based medicine, this article proposed the construction of "clinical syndrome-based medicine" based on the optimal clinical experience, which was suitable for the characteristics of TCM clinical practice. The key to clinical syndrome-based medicine is the optimal clinical experience, and the core elements of the optimal clinical experience are regularity and reproducibility. Real-world research methods are recommended as a reference for obtaining the optimal clinical experience. Clinical syndrome-based medicine, combining the characteristics of TCM clinical practice and incorporating the concept of evidence-based medicine, is the product of integrating TCM into evidence-based medicine. It is dedicated to improving the clinical efficacy of TCM along with evidence-based medicine.

Association of carbohydrate intake from different sources with all-cause and cardiovascular mortality among chronic kidney disease populations: assessment of 1999-2018 National Health and Nutrition Examination Survey participation.

This study analysed the data from the NHANES (1999-2018) to examine how different sources of carbohydrate intake affected the all-cause and cardiovascular mortality of 11,302 chronic kidney disease (CKD) patients. The data were adjusted for other factors using various methods. The results showed that CKD patients (stages 1-2 and 3-5) who consumed more carbohydrates from whole grains, fruits, vegetables and less carbohydrates from fruit juice or sauces had lower mortality rates. Replacing fat intake with carbohydrates from whole grains (HR = 0.86[0.78-0.95]), fruits (raw) (HR = 0.79[0.70-0.88]) and non-starchy vegetables (HR = 0.82[0.70-0.96]), but not protein intake, was linked to lower all-cause mortality. The fibre content in carbohydrates might partly account for the benefits of selected carbohydrate intake. This study provided practical recommendations for optimising the carbohydrate sources in CKD patients.

Impact of inflammation and anti-inflammatory modalities on diabetic cardiomyopathy healing: From fundamental research to therapy.

Diabetic cardiomyopathy (DCM) is a prevalent cardiovascular complication of diabetes mellitus, characterized by high morbidity and mortality rates worldwide. However, treatment options for DCM remain limited. For decades, a substantial body of evidence has suggested that the inflammatory response plays a pivotal role in the development and progression of DCM. Notably, DCM is closely associated with alterations in inflammatory cells, exerting direct effects on major resident cells such as cardiomyocytes, vascular endothelial cells, and fibroblasts. These cellular changes subsequently contribute to the development of DCM. This article comprehensively analyzes cellular, animal, and human studies to summarize the latest insights into the impact of inflammation on DCM. Furthermore, the potential therapeutic effects of current anti-inflammatory drugs in the management of DCM are also taken into consideration. The ultimate goal of this work is to consolidate the existing literature on the inflammatory processes underlying DCM, providing clinicians with the necessary knowledge and tools to adopt a more efficient and evidence-based approach to managing this condition.

Lobetyolin Alleviates Ferroptosis of Skeletal Muscle in 5/6 Nephrectomized Mice via Activation of Hedgehog-GLI1 Signaling.

BACKGROUND: Muscle wasting increases morbidity and mortality and is related to chronic kidney disease (CKD) and dialysis. It is still unclear whether ferroptosis occurs during this progression and whether it is a potential intervention target for the treatment of CKD-related muscle injury. PURPOSE: The objective is to identify potential compounds for treating ferroptosis and muscle wasting and explore the potential mechanisms in vivo/in vitro. METHODS: Initially, we explored whether ferroptosis is present in the skeletal muscle of 5/6 nephrectomized (NPM) mice via RNA-Seq analysis, TUNEL staining, Oil red O staining, MDA/GSH/GSSG level detection and real-time quantitative PCR (qPCR). Subsequently, utilizing our established molecular phenotyping strategy, we screened potential traditional Chinese herb-derived compounds for alleviation of muscle wasting and ferroptosis. HE staining, Oil red O staining, TUNEL staining, immunofluorescence staining, MDA/GSH/GSSG level detection, Fe level detection, western blotting and qPCR were applied to assess the effects of the identified compound on muscle wasting and ferroptosis and explore the potential mechanism. Furthermore, RNA-Seq analysis, ChIP-Seq analysis and further experiments in vitro were performed to determine the role of Hedgehog signaling in the effect of Lobetyolin (LBT) on ferroptosis. RESULTS: In NPM mice, skeletal muscle dysfunction, lipogenesis, reduced GSH/GSSG ratio, decreased GSH content, increased MDA production and and higher levels of ferroptosis markers were observed. LBT treatment (30 mg/kg or 50 mg/kg) significantly alleviates skeletal muscle injury by inhibiting ferroptosis. Additionally, in an in vitro investigation, C2C12 cells exposed to Indolyl sulfate (IS) induced ferroptosis and LBT treatment (20 µM and 50 µM) protected C2C12 from such injury, consistent with the results from the in vivo analysis. Furthermore, it was found LBT increased the levels of protein involving Hedgehog signaling pathway (SMO and GLI1), and rescue analysis revealed that this pathway played a crucial role in the regulation of ferroptosis. Further experiments demonstrated that LBT upregulated a series of suppressors of ferroptosis by activating Gli1 transcription. CONCLUSION: LBT alleviates CKD-induced muscle injury by inhibiting ferroptosis through activation of the Hedgehog signaling pathway.

A molecular phenotypic screen reveals that lobetyolin alleviates cardiac dysfunction in 5/6 nephrectomized mice by inhibiting osteopontin.

BACKGROUND: Cardiovascular diseases are the major cause of mortality in patients with advanced chronic kidney diseases. The predominant abnormality observed among this population is cardiac dysfunction secondary to myocardial remodelings, such as hypertrophy and fibrosis, emphasizing the need to develop potent therapies that maintain cardiac function in patients with end-stage renal disease. AIMS: To identify potential compounds and their targets as treatments for cardiorenal syndrome type 4 (CRS) using molecular phenotyping and in vivo/in vitro experiments. METHODS: Gene expression was assessed using bioinformatics and verified in animal experiments using 5/6 nephrectomized mice (NPM). Based on this information, a molecular phenotyping strategy was pursued to screen potential compounds. Picrosirius red staining, wheat germ agglutinin staining, Echocardiography, immunofluorescence staining, and real-time quantitative PCR (qPCR) were utilized to evaluate the effects of compounds on CRS in vivo. Furthermore, qPCR, immunofluorescence staining and flow cytometry were applied to assess the effects of these compounds on macrophages/cardiac fibroblasts/cardiomyocytes. RNA-Seq analysis was performed to locate the targets of the selected compounds. Western blotting was performed to validate the targets and mechanisms. The reversibility of these effects was tested by overexpressing Osteopontin (OPN). RESULTS: OPN expression increased more remarkably in individuals with uremia-induced cardiac dysfunction than in other cardiomyopathies. Lobetyolin (LBT) was identified in the compound screen, and it improved cardiac dysfunction and suppressed remodeling in NPM mice. Additionally, OPN modulated the effect of LBT on cardiac dysfunction in vivo and in vitro. Further experiments revealed that LBT suppressed OPN expression via the phosphorylation of c-Jun N-terminal protein kinase (JNK) signaling pathway. CONCLUSIONS: LBT improved CRS by inhibiting OPN expression through the JNK pathway. This study is the first to describe a cardioprotective effect of LBT and provides new insights into CRS drug discovery.

Malignant peritoneal mesothelioma with massive ascites as the first symptom: A case report.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare tumor with nonspecific clinical manifestations, which is extremely difficult to diagnose. Herein, we reported a case of MPM in the abdominal cavity with massive short-term ascites as the first symptom. CASE SUMMARY: A 65-year-old woman presented to the hospital with abdominal pain, distention, and shortness of breath that persisted for 15 d. The serum CA-125 level was 1075 U/mL. The abdominal computed tomography showed massive ascites and no obvious tumor lesions. The pathological examination of the ascitic fluid showed numerous heterotypic cells with some papillary structures. The immunohistochemistry and fluorescence in situ hybridization showed the deletion of CDX2 (-), WT-1 (-), Ki-67 (about 10% +), CEA (-), Glut-1 (+++), desmin (-), PD-L1 (-), and CDKN2A (P16). The final diagnosis was MPM. The patient refused tumor cytoreductive surgery and received two cycles of cisplatin plus pemetrexed bidirectional chemotherapy. In the second cycle, she received an additional cycle of hyperthermic intraperitoneal chemotherapy and immune checkpoint inhibitor therapy due to massive recalcitrant ascites. She died of disease progression 2 mo after diagnosis. CONCLUSION: In case of massive unexplained ascites, the possibility of MPM should not be excluded to avoid misdiagnosis and delay in treatment.

[Types of clinical data and statistical methodology of human use experience in traditional Chinese medicine].

Application experience in humans, a summary of the clinical practice of traditional Chinese medicine(TCM), serves as an important data source for evaluating the safety, effectiveness, and clinical value of drugs in the development of new Chinese medicine. The collected data serving as the evaluation evidence through statistical analysis are critical to the research on the application experience in humans. This article summarized and analyzed the data characteristics and statistical methodology of application experience of Chinese medicine in humans, and concluded the data types, outcome evaluation, bias evaluation, confounding factors, and missing values. Furthermore, the article emphasized the importance of data analysis of application experience of Chinese medicine in humans for TCM evidence and put forward the current difficulties, such as low data quality and large internal bias, lack of individualized data processing methods, and lack of methods for "disease-syndrome combination" data. We believe that with the development of methodology, the application experience of Chinese medicine in humans can strongly support the development of new drugs in TCM.

Intermittent appearance of right coronary fistula and collateral circulation: A case report.

BACKGROUND: Congenital coronary artery fistula can lead to symptoms of chest tightness, chest pain, or exertional dyspnea, which is a congenital vascular malformation that should not be ignored. Patients who have such malformations are frequently observed with different concurrent abnormal anatomic structures. Collateral circulation may have a positive effect on improving the patients' symptoms. CASE SUMMARY: A 53-year-old female experienced episodic chest discomfort for the past month with symptoms manifesting when she was agitated or overexerted. After a positive treadmill test, the patient underwent coronary angiography. "Ghostlike" intermittent appearance of coronary ventricular fistula and collateral branching were observed. The patient was diagnosed with a right coronary ventricular fistula and collateral circulation. CONCLUSION: This case shows the likelihood of collateral circulation in patients with coronary artery fistula. This may provide medical staff with novel solutions to treat insufficiency of myocardial blood supply induced by cardiovascular malformations.

[Medication rules of traditional Chinese medicine for the treatment of premature ejaculation: An analysis based on data mining].

OBJECTIVE: To study the medication rules of traditional Chinese medicine (TCM) in the treatment of premature ejaculation. METHODS: We searched the databases of CNKI, Wan Fang, VIP, SinoMed (CBM) and PubMed for studies on the treatment of PE with TCM prescriptions and performed statistical analyses on the data obtained using the TCM inheritance auxiliary platform software. RESULTS: Totally 180 prescriptions were identified, involving 209 TCM drugs. The results of statistical analysis showed that the TCM drugs for the treatment of premature ejaculation were mostly warm, flat or cold in nature, sweet or spicy in taste, and with the kidney, liver and spleen meridian tropisms. The single TCM drugs most commonly used included Lycium barbarum L (Gouqizi), followed by Epimedium brevicornum Maxim (Yinyanghuo), Os draconis (Longgu), Fructus rosae laevigatae (Jinyingzi), and the drugs most frequently used in combination with others in a prescription were Os draconis (Longgu) and Concha ostreae (Muli). Seven newly derived prescriptions were identified in addition. CONCLUSIONS: The compatibility of TCM in the treatment of premature ejaculation is characterized by the combination of the drugs for tonifying the kidney and arresting seminal emission as the main medication strategy, with those for soothing the liver and invigorating the spleen as the adjuvant agents, which has a certain clinical application value.

Isolation and characterization of an operon involved in sulfate and sulfite metabolism in Sinorhizobium fredii.

A gene cluster ORFabcd from a Sinorhizobium fredii HN01 mutant strain HSMRalpha was isolated. We showed that it was an operon involved in sulfur metabolism. Functional studies revealed that, except for ORFb, the three genes ORFa, ORFc and ORFd were involved in sulfite reduction. ORFa and ORFc were similar to the cysG and cysI from Sinorhizobium meliloti 1021 and Rhizobium etli CFN 42, respectively. ORFd encodes a conserved hypothetical protein in other bacteria. We demonstrate here, for the first time, that it was a new locus involved in sulfate assimilation in S. fredii HN01 and we designated it as cysII.

[Cloning and diversity analysis of microorganism genes from alkalescence soil].

The metagenomic DNAs were extracted and purified from alkalescence environmental samples directly. On the basis of the metagenomic DNA, the alkaline soil 16S rDNA library composed of 5,562 positive clones was constructed. The phylogenic tree indicated that the bacteria from the alkaline soils were bio-diversity. The metagenomic DNA library named AL01 was constructed by inserting restriction fragments of the purified DNAs into plasmids pGEM-3Zf(+) vector. This library contained 23,650 positive clones and the average foreign DNA fragments were about 3.2 kb. The length of the library covered 75.68 Mb. The efficiency of the metagenomic library was approximately 6,000 clones from 1g dry soil samples. After screening AL01 DNA library with the screening tactics of enzymes, we confirmed that a positive clone, designated pGXAA2011, contained an alkaline protease gene AP01. Enzymatic analysis proved that its reaction optimum pH was 9.5 and the optimum temperature was 40 degrees C. Furthermore, a clone, designated pGXAG142 was screened from metagenomic DNA library, which expresses beta-glucosidase. DNA sequence indicated that the potential ORF of pGXAG142, which was named unglu01, there was no DNA or amino acids identity with the known beta-glucosidase genes in the Genbank. The integrated ORF was cloned into pETBlue-2 vector and was then transformed into Tuner(DE3)pLacI. The recombinant expression clone could express beta-glucosidase on the screening plate clearly and the analysis of SDS-PAGE indicated that the target protein was about 29 kDa.