Methods to increase the diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: An updated review.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a means to procure adequate specimens for histological and cytologic analysis. The ideal EUS-FNA should be safe, accurate, and have a high sample adequacy rate and low adverse events rate. In recent years, many guidelines and trials on EUS-FNA have been published. The purpose of this article is to provide an update on the influence of some of the main factors on the diagnostic efficiency of EUS-FNA as well as a rare but serious complication known as needle tract seeding.

Role of albumin-bilirubin score in non-malignant liver disease.

The albumin-bilirubin (ALBI) score, which was proposed to assess the prognosis of patients with hepatocellular carcinoma, has gradually been extended to other liver diseases in recent years, including primary biliary cholangitis, liver cirrhosis, hepatitis, liver transplantation, and liver injury. The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models. It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators. An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease; additionally, it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases, such as decompensation events. This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

Diagnostic value of endoscopic ultrasound in pelvic masses with bowel involvement.

BACKGROUND: The diagnostic ability of endoscopic ultrasound (EUS) for intestinal infiltration by pelvic masses has aroused considerable interest in many oncological settings. This study aimed to evaluate the effectiveness of EUS in predicting colorectal invasion in patients with pelvic masses and compare its accuracy with that of other imaging methods, namely pelvic MRI and abdominal computed tomography (CT), in predicting intestinal involvement in patients with histologically confirmed colorectal invasion. METHODS: A hundred and eighty-four female patients with histologically confirmed benign or malignant pelvic masses were enrolled in a retrospective-prospective study. All patients underwent EUS, pelvic MRI, and one or more of abdominal CT, transvaginal sonography, and colonoscopy examinations before surgery. The surgical and pathological results were used as the gold standard to evaluate the diagnostic accuracy of EUS for colorectal invasion of pelvic masses. RESULTS: This study included 184 patients who underwent surgery, with the time between EUS and surgery ranging from 1 to 309 (mean, 13.2) days. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of EUS for benign and malignant pelvic masses infiltrating the intestine were 83.3, 97.8, 99.1, and 66.2%, respectively. The overall diagnostic accuracy was 87.0%. CONCLUSIONS: EUS is a simple, noninvasive, reliable, and accurate technique for the preoperative diagnosis of pelvic masses infiltrating the intestine. The authors recommend the use of this technology by gynecologists, as well as its incorporation into the preoperative diagnostic process to determine the most suitable surgical method. This would help in avoiding unexpected situations and unnecessary resource wastage during surgery.

Standardized construction of a porcine model for acute obstructive jaundice and training of endoscopic ultrasound-guided choledochoduodenostomy.

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP) for patients with obstructive jaundice. However, it is still a challenge for many endoscopists because of its novelty and complexity. This study aimed to establish an ideal bile duct dilatation model for the training and practice of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS). Methods: The 34 healthy Bama miniature pigs were divided into the part of developing the standardized EUS-CDS (n=9) and the part of trainees training (n=25). Part one, two different methods were used to clip Vater's ampulla using metal clips to establish an extrahepatic bile duct dilatation model. Part two, five trainees were trained on EUS-CDS with 25 pigs. Following a 2-week observation period, the feasibility and effectiveness of the technique were evaluated. Results: In the group with three metal clips perpendicular to the duodenal wall clipping Vater's ampulla, the success rate of extrahepatic bile duct dilation greater than 1 cm in 24 h was 5/6, whereas the remaining one pig was 48 h. All five trainees can finally complete the EUS-CDS independently. No death occurred during the 2-week observation period. Conclusion: Clipping Vater's ampulla with three metal clips perpendicular to the duodenal wall is an effective and stable method to create a porcine bile duct dilatation model.

Diagnostic value of endoscopic ultrasound in groove pancreatitis.

Aim: Groove pancreatitis (GP) is a rare type of chronic pancreatitis characterized by varying degrees of thickening and scarring of the duodenal wall, duodenal lumen stenosis, mucosal hypertrophy with plicae and cyst formation. GP is primarily observed in middle-aged male patients with a history of alcohol consumption. Clinical symptoms are usually non-specific, and there is currently no unified diagnostic standard. However, imaging methods, particularly endoscopic ultrasound (EUS), are useful for diagnosis. EUS-guided biopsy can provide a strong basis for the final diagnosis. This review summarizes the value of EUS and its derivative technologies in the diagnosis, differential diagnosis and treatment of GP.Methods: After searching in PubMed and Web of Science databases using 'groove pancreatitis (GP)' and 'endoscopic ultrasonography (EUS)' as keywords, studies related were compiled and examined.Results: EUS and its derivative technologies are of great significance in the diagnosis, differential diagnosis, and treatment of GP, but there are still limitations that need to be comprehensively applied with other diagnostic methods to obtain the most accurate results.Conclusion: EUS has unique value in both the diagnosis and treatment of GP. Clinicians need to be well-versed in the advantages and limitations of EUS for GP diagnosis to select the most suitable imaging diagnostic method for different cases and to reduce the unnecessary waste of medical resources.

Clinical application and follow-up of electrocautery-enhanced lumen-apposing metal stents for endoscopic ultrasonography-guided interventions.

Aim: The lumen-apposing metal stent (LAMS) is a new device that expands the scope of gastrointestinal intervention under endoscopy. LAMS was initially used for the treatment of pancreatic fluid collections (PFCs), but is increasingly being used off-label. The electrocautery system simplifies the deployment of LAMS, making it more suitable for off-label situations. The short-term results of electrocautery-enhanced lumen-apposing metal stents (ECE-LAMS) are satisfactory; however, the long-term follow-up results must be evaluated. The aim of this article is to review the expanded clinical application of ECE-LAMS, the clinical value of on-label and off-label use, and follow-up results.Methods: After searching in PubMed and Web of Science databases using 'electrocautery-enhanced lumen-apposing metal stents' and 'endoscopic ultrasonography (EUS) -guided interventions' as keywords, studies related were compiled and examined.Results: ECE-LAMS are widely used for on-label and off-label situations. The short-term and long-term results of ECE-LAMS are satisfactory, but there are still some studies that do not agree with this viewpoint.Conclusion: The clinical application of ECE-LAMS is relatively safe and reliable but more well-designed randomized trials and prospective studies are needed to evaluate the impact of this technology on therapeutic EUS, to improve the safety and success rate of EUS-guided LAMS implantation, and to expand its application in other indications.

The vascular and morphological characteristics of tumors under narrow-band imaging as predictors for the grade and stage of bladder cancer: a prospective and multi-center study.

The vascular and morphological features of tumors are important predictors of the nature, grade, and stage of various cancers. However, this association has not been tested in bladder cancer. The aim of our study was to investigate the correlation between the morphological characteristics of tumor vessels and the nature, stage and grade of bladder cancer. Between November 2021 and March 2023, we prospectively collated clinical information and cystoscopy information from a series of patients with bladder cancer. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for the nature, grade and stage of bladder cancer. Our analysis showed that cauliflower-like tumors, dotted vessels, and circumferential vessels were independent risk factors for bladder cancer. Reticular vessels were an independent risk factor for high-grade bladder cancer. Thick branching vessels in bladder tumors, along with a wide base, were independent risk factors for the invasion of bladder cancer into the lamina propria. Primary diagnosis, lesion location (beside the left ureteral orifice) and obscure lesion boundaries were all identified as independent risk factors for muscle invasive bladder cancer.

H2O2 enhances the spontaneous phasic contractions of isolated human-bladder strips via activation of TRPA1 channels on sensory nerves and the release of substance P and PGE2.

Several studies have indicated that reactive oxygen species (ROS) can lead to detrusor overactivity (DO), but the underlying mechanisms are not known. Hydrogen dioxide (H2O2) is used commonly to investigate the effects of ROS. In present study, we investigated the effects of H2O2 on phasic spontaneous bladder contractions (SBCs) of isolated human-bladder strips (iHBSs) and the underlying mechanisms. Samples of bladder tissue were obtained from 26 patients undergoing cystectomy owing to bladder cancer. SBCs of iHBSs were recorded in organ-bath experiments. H2O2 (1µM-10mM) concentration-dependently increased the SBCs of iHBSs. These enhancing effects could be mimicked by an agonist of transient receptor potential (TRP)A1 channels (allyl isothiocyanate) and blocked with an antagonist of TRPA1 channels (HC030031; 10 µM). H2O2 induced enhancing effects also could be attenuated by desensitizing sensory afferents with capsaicin (10 µM), blocking nerve firing with TTX (1 µM), blocking neurokinin effects with NK2 receptor antagonist (SR48968, 10 µM), and blocking PGE2 synthesis with indomethacin (10 µM), respectively. Our study: (i) suggests activation of TRPA1 channels on bladder sensory afferents, and then release of substance P or PGE2 from sensory nerve terminals, contribute to the H2O2-induced enhancing effects on SBCs of iHBSs; (ii) provides insights for the mechanisms underlying ROS leading to DO; (iii) indicates that targeting TRPA1 channels might be the promising strategy against overactive bladder in conditions associated with excessive production of ROS.

Development and validation of a predictive model for the diagnosis of bladder tumors using narrow band imaging.

PURPOSE: At present, the prediction of bladder tumor nature during cystoscopy is partially dependent on the clinician's own experience. Subjective factors may lead to excessive biopsy or delayed treatment. The purpose of our study is to establish a reliable model for predicting the nature of bladder tumors using narrow band imaging. METHODS: From November 2021 to November 2022, the clinical data of 231 patients who required a cystoscopy were prospectively collected at our center. Cystoscopy was performed in 219 eligible patients, in which both tumor and vascular morphology characteristics were recorded. Pathological results were used as the diagnostic standard. A logistic regression analysis was used to screen out factors related to tumor pathology. Bootstrap resampling was used for internal validation. A total of 71 patients from four other centers served as an external validation cohort. RESULTS: The following diagnostic factors were identified: tumor morphology (cauliflower-like or algae-like lesions), vascular morphology (dotted or circumferential vessels), tumor boundary (clear or unclear), and patients' symptoms (gross hematuria) and were included in the prediction model. The internal validation results showed that the area under the curve was 0.94 (95% CI 0.92-0.97), and the P value from the goodness-of-fit test was 0.97. After external validation, the results showed the area under the curve was 0.89 (95% CI 0.82-0.97) and the P value of the goodness-of-fit test was 0.24. CONCLUSION: A diagnostic prediction nomogram was established for bladder cancer. The verification results showed that the prediction model has good prediction performance.

Activation of TRPA1 in Bladder Suburothelial Myofibroblasts Counteracts TGF-ß1-Induced Fibrotic Changes.

The activation of the transient receptor potential ankyrin 1 (TRPA1) channel has anti-fibrotic effects in the lung and intestine. Suburothelial myofibroblasts (subu-MyoFBs), a specialized subset of fibroblasts in the bladder, are known to express TRPA1. However, the role of the TRPA1 in the development of bladder fibrosis remains elusive. In this study, we use the transforming growth factor-ß1 (TGF-ß1) to induce fibrotic changes in subu-MyoFBs and assess the consequences of TRPA1 activation utilizing RT-qPCR, western blotting, and immunocytochemistry. TGF-ß1 stimulation increased α-SMA, collagen type I alpha 1 chain(col1A1), collagen type III (col III), and fibronectin expression, while simultaneously suppressing TRPA1 in cultured human subu-MyoFBs. The activation of TRPA1, with its specific agonist allylisothiocyanate (AITC), inhibited TGF-ß1-induced fibrotic changes, and part of these inhibition effects could be reversed by the TRPA1 antagonist, HC030031, or by reducing TRPA1 expression via RNA interference. Furthermore, AITC reduced spinal cord injury-induced fibrotic bladder changes in a rat model. The increased expression of TGF-ß1, α-SMA, col1A1 and col III, and fibronectin, and the downregulation of TRPA1, were also detected in the mucosa of fibrotic human bladders. These findings suggest that TRPA1 plays a pivotal role in bladder fibrosis, and the negative cross talk between TRPA1 and TGF-ß1 signaling may represent one of the mechanisms underlying fibrotic bladder lesions.

Diagnostic value of endoscopic ultrasonography in pelvic masses with bowel involvement.

Benign and malignant pelvic masses with or without intestinal invasion are common in women of childbearing age. Patients may have nonspecific symptoms and signs or experience no symptoms. Laparoscopic resection of pelvic masses is currently the mainstream treatment; therefore, accurate preoperative evaluation is not only essential for patients suspected of having intestinal invasion, but also extremely important for the selection of follow-up treatment. Procedures, including endoscopic ultrasonography (EUS), pelvic magnetic resonance imaging, abdominal computed tomography, vaginal ultrasonography, barium enema, and colonoscopy, aid in determining the presence, depth, and histology of the disease. In particular, the wide application and continuous developments in EUS techniques have improved the diagnostic accuracy for intestinal subepithelial and peripheral organ lesions. This article reviewed the clinical value of EUS in the diagnosis of benign and malignant pelvic masses with bowel involvement.

Organoids to Remodel SARS-CoV-2 Research: Updates, Limitations and Perspectives.

The novel COVID-19 pneumonia caused by the SARS-CoV-2 virus poses a significant threat to human health. Scientists have made significant efforts to control this virus, consequently leading to the development of novel research methods. Traditional animal and 2D cell line models might not be suitable for large-scale applications in SARS-CoV-2 research owing to their limitations. As an emerging modelling method, organoids have been applied in the study of various diseases. Their advantages include their ability to closely mirror human physiology, ease of cultivation, low cost, and high reliability; thus, they are considered to be a suitable choice to further the research on SARS-CoV-2. During the course of various studies, SARS-CoV-2 was shown to infect a variety of organoid models, exhibiting changes similar to those observed in humans. This review summarises the various organoid models used in SARS-CoV-2 research, revealing the molecular mechanisms of viral infection and exploring the drug screening tests and vaccine research that have relied on organoid models, hence illustrating the role of organoids in remodelling SARS-CoV-2 research.

Piezo2 Channel Upregulation is Involved in Mechanical Allodynia in CYP-Induced Cystitis Rats.

Mechanical sensing Piezo2 channel in primary sensory neurons has been shown contribute to mechanical allodynia in somatic chronic pain conditions. Interstitial cystitis (IC)-associated pain is often triggered by bladder filling, a presentation that mimics the mechanical allodynia. In the present study, we aimed to examine the involvement of sensory Piezo2 channel in IC-associated mechanical allodynia using a commonly employed cyclophosphamide (CYP)-induced IC model rat. Piezo2 channels in dorsal root ganglia (DRGs) was knocked down by intrathecal injections of Piezo2 anti-sense oligodeoxynucleotides (ODNs) in CYP-induced cystitis rats, and mechanical stimulation-evoked referred bladder pain was measured in the lower abdomen overlying the bladder using von Frey filaments. Piezo2 expression at the mRNA, protein, and functional levels in DRG neurons innervating the bladder was detected by RNA-fluorescence in situ hybridization, western blotting, immunofluorescence, and Ca2+ imaging, respectively. We found that Piezo2 channels were expressed on most (> 90%) of the bladder primary afferents, including afferents that express CGRP, TRPV1 and stained with isolectin B4. CYP-induced cystitis was associated with Piezo2 upregulation in bladder afferent neurons at the mRNA, protein, and functional levels. Knockdown of Piezo2 expression in DRG neurons significantly suppressed mechanical stimulation-evoked referred bladder pain as well as bladder hyperactivity in CYP rats compared to CYP rats treated with mismatched ODNs. Our results suggest upregulation of Piezo2 channels is involved in the development of bladder mechanical allodynia and bladder hyperactivity in CYP-induced cystitis. Targeting Piezo2 might be an attractive therapeutic approach for IC-related bladder pain.

Central nervous system efficacy of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small cell lung cancer: a pooled analysis from two phase 2 studies.

BACKGROUND: Furmonertinib (AST2818) is a brain penetrant pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR sensitizing mutations and T790M mutation. We report the pooled central nervous system (CNS) efficacy data of furmonertinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC) from two phase 2 studies. METHODS: This was a pooled, post-hoc analysis of two phase 2 studies (NCT03127449 [phase 2a study of furmonertinib], NCT03452592 [phase 2b study of furmonertinib]). In the phase 2a study, patients received furmonertinib 40 mg, 80 mg, 160 mg, or 240 mg orally once daily. In the phase 2b study, all patients received furmonertinib 80 mg orally once daily. CNS efficacy of furmonertinib was analyzed in patients with baseline CNS lesions by an independent review center per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: A total of 132 patients with baseline CNS metastases were included in this analysis. In 52 patients with measurable CNS lesions, CNS objective response rates were zero (0/1), 65% (22/34), 85% (11/13), and 25% (1/4), and CNS disease control rates were zero (0/1), 97% (33/34), 100% (13/13), and 100% (4/4) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. In patients with measurable or non-measurable CNS lesions, median CNS progression-free survival was 2.8 months (95% confidence interval [CI] 1.4-8.3), 11.6 months (95% CI 8.3-13.8), 19.3 months (95% CI 5.5-not available [NA]), and not reached (95% CI 2.8 months-NA) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. CONCLUSIONS: Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC. TRIAL REGISTRATION: Both studies were registered on ClinicalTrial.gov. The phase 2a study was registered with NCT03127449 on April 25, 2017; The phase 2b study was registered with NCT03452592 on March 2, 2018.

The location of estrogen receptor variant ER-α36 is associated with the invasion of glioblastoma.

Glioblastoma (GBM) is the most common central nervous system tumor and is associated with poor outcomes. There have been no significant improvements in GBM mortality in recent decades. ER-α36 is a variant of ER-α66 that may be involved in carcinoma growth and proliferation via genomic and nongenomic mechanisms. This variant might play an essential role in tamoxifen resistance of several tumors. Previously, our laboratory found that ER-α36 is expressed in GBM and participates in proliferation; nevertheless, the role of ER-α36 in GBM invasion remains unknown. This study aimed to determine the effects of the ER-α36 modulator SNG162 on GBM growth and invasion. U251 cells, U87cells, and U87-36KD cells with knockdown of ER-α36 expression were cultured under the two-dimensional and the three-dimensional (3D) environments. GBM cells growth was examined by cell counting, flow cytometry, western blot, and MTT assays. Invasiveness was measured using confocal microscopy in the 3D environment. Growth of U87 cells with downregulated EGFR and ER-α36 expression was significantly reduced after treatment with 1 µM, 3 µM, and 5 µM of SNG162; growth inhibition in U251 cells was more potent than in U87 cells, although the expression level of ER-α36 in U251 cells was lower than in U87 cells. We found that 1 µM SNG162 suppressed E2-induced MAPK/ERK pathway activation in U87 cells. We also showed that SNG162 inhibited U87 cells invasion; however, it did not significantly affect U251 and U87-36KD cells invasion using the 3D culture method. Finally, we determined that ER-α36 was expressed in the nucleus of invading GBM cells, and SNG162 significantly inhibited the expression of ER-α36 in these cells. SNG162 inhibited the expression of EGFR on cell membranes of non-invasive GBM cells. These results suggest that SNG162 could be a therapeutic agent for GBM by targeting ER-α36.

EUS-guided interventional therapies for pancreatic diseases.

Endoscopic ultrasound (EUS) is an integrated diagnostic technique merging endoscope and ultrasound to examine the digestive system. EUS has emerged as a primary diagnostic method for pancreatic diseases due to its distinctive benefits. Over the past four decades, EUS has undergone a transformation, shifting its role from primarily diagnostic to increasingly therapeutic. Additionally, in recent years, EUS has emerged as an increasingly prominent adjunctive or alternative approach to conventional surgical interventions. This review provides a comprehensive analysis of current technological approaches in the treatment of pancreatic diseases. The dynamic interplay with diverse therapeutic approaches has reinvigorated EUS and shaped its trajectory in the management of pancreatic diseases.

Exploring KRAS-mutant pancreatic ductal adenocarcinoma: a model validation study.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all solid tumors. Tumorigenesis is promoted by the oncogene KRAS, and KRAS mutations are prevalent in patients with PDAC. Therefore, a comprehensive understanding of the interactions between KRAS mutations and PDAC may expediate the development of therapeutic strategies for reversing the progression of malignant tumors. Our study aims at establishing and validating a prediction model of KRAS mutations in patients with PDAC based on survival analysis and mRNA expression. Methods: A total of 184 and 412 patients with PDAC from The Cancer Genome Atlas (TCGA) database and the International Cancer Genome Consortium (ICGC), respectively, were included in the study. Results: After tumor mutation profile and copy number variation (CNV) analyses, we established and validated a prediction model of KRAS mutations, based on survival analysis and mRNA expression, that contained seven genes: CSTF2, FAF2, KIF20B, AKR1A1, APOM, KRT6C, and CD70. We confirmed that the model has a good predictive ability for the prognosis of overall survival (OS) in patients with KRAS-mutated PDAC. Then, we analyzed differential biological pathways, especially the ferroptosis pathway, through principal component analysis, pathway enrichment analysis, Gene Ontology (GO) enrichment analysis, and gene set enrichment analysis (GSEA), with which patients were classified into low- or high-risk groups. Pathway enrichment results revealed enrichment in the cytokine-cytokine receptor interaction, metabolism of xenobiotics by cytochrome P450, and viral protein interaction with cytokine and cytokine receptor pathways. Most of the enriched pathways are metabolic pathways predominantly enriched by downregulated genes, suggesting numerous downregulated metabolic pathways in the high-risk group. Subsequent tumor immune infiltration analysis indicated that neutrophil infiltration, resting CD4 memory T cells, and resting natural killer (NK) cells correlated with the risk score. After verifying that the seven gene expression levels in different KRAS-mutated pancreatic cancer cell lines were similar to that in the model, we screened potential drugs related to the risk score. Discussion: This study established, analyzed, and validated a model for predicting the prognosis of PDAC based on risk stratification according to KRAS mutations, and identified differential pathways and highly effective drugs.

Comparative efficacy of exercise modalities for cardiopulmonary function in hemodialysis patients: A systematic review and network meta-analysis.

Background: To provide reliable evidence to exercise rehabilitation therapists and clinicians, we compared and analyzed the effects of different exercise modalities on cardiopulmonary function in hemodialysis patients using Bayesian network meta-analysis. Methods: PubMed, OVID, Web of Science, Cochrane Library, Embase, Scopus, CINAHL, SPORT Discus, SinoMed, CNKI, Wanfang, and VIP were searched from inception to July 20, 2022. We included randomized controlled trials comparing 12 exercise modalities to improve cardiorespiratory fitness in hemodialysis patients. All statistical analysis was performed using STATA and R. Result: A total of 82 randomized controlled trials involving 4146 maintenance hemodialysis patients were included in this study. The pair-wise meta-analysis showed that all exercise modalities had a positive effect on all indicators of cardiorespiratory capacity. The network meta-analysis demonstrated that Blood flow restriction training (BFRT), Cycle exercise (CE), Inspiratory muscle training (IMT), Combined aerobic and resistance training (CT), and Aerobic training (AT) were significantly better than usual care for 6-min walkability; Medium intensity continuous training (MICT), CT, CE, and AT were considerably better than usual care for VO2Peak; body and mind training (MBT) and CT significantly improved SBP compared to usual care; and only MBT was significantly better than usual care for DBP. Both the two-dimensional plot and the radar plot demonstrated that CT had the best combined-effect on each index of cardiorespiratory fitness. Subgroup and sensitivity analyses demonstrated the robustness of the results. The evidence was mainly "low" to "very low" for this network meta-analysis. Conclusion: There is no one exercise that can achieve the best effect on all of the outcomes. The benefits of MBT in decreasing arterial blood pressure are unsurpassed by other exercise methods. The intervention effect of the CT is better and more stable. Electrical muscle stimulation training (MEST) can be employed in individuals who do not wish to exercise actively but may cause an increase in blood pressure. On the basis of the characteristics of different exercise types, guidelines developers, clinicians, and patients may employ them appropriately. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Development and Validation of a UPLC-MS/MS Method for the Quantification of Components in the Ancient Classical Chinese Medicine Formula of Guyinjian.

Guyinjian (GYJ) is an ancient classic formula of traditional Chinese medicine used for the treatment of liver and kidney yin deficiency; it was derived from the book "Jing Yue Quan Shu" in the Ming Dynasty. Modern clinical observation experiments have shown that GYJ has a definite therapeutic effect on the treatment of gynecological diseases such as kidney deficiency type oligomenorrhea, climacteric syndrome, intermenstrual bleeding, pubertal metrorrhagia, etc. However, the lack of GYJ quality control studies has greatly limited the development of its wider clinical application. In this study, a validated UPLC-MS/MS method was developed successfully for the first time and used to quantify fourteen compounds in GYJ samples with good specificity, linearity (r = 0.9960-0.9999), precision (RSD% ≤ 3.18%), stability (RSD% ≤ 2.22%) and accuracy (recovery test within 88.64-107.43%, RSD% at 2.82-6.22%). Simultaneously, the determination results of 15 batches of GYJ samples were analyzed by multivariate statistical methods, and it was found that the compounds have a greater influence on batch-to-batch stability, mainly Rehmannioside D, Loganin, Morroniside, Ginsenoside Re, and 3',6-Disinapoylsucrose. The proposed new method has the advantages of high sensitivity, high selectivity, and rapid analysis, which provides a reference for the GYJ quality control study.