ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine （5-HT） signaling pathway in rats with functional dyspepsia （FD） and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， model group， mosapride group （1.575 mg·kg^-1）， and Yueju Wan low-， medium-， and high-dose groups （0.735， 1.47， and 2.94 g·kg^-1， respectively）. The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling， rats were administered the corresponding drugs by gavage for 28 days. After treatment， gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT， tryptophan hydroxylase （TPH）， and substance P （SP） were detected by enzyme-linked immunosorbent assay （ELISA）， and acetylcholine （ACh） levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor （5-HT4R）， SP， and acetylcholinesterase （AChE） in colon tissue， as well as 5-hydroxytryptamine 3 receptor （5-HT3R）， SP， and AChE in hypothalamic tissue. Immunohistochemistry （IHC） was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group， the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased （P<0.01）. Serum levels of 5-HT， SP， ACh， and TPH were significantly reduced （P<0.01）. Histopathological examination revealed irregular arrangement of glands in the gastric antrum， slight mucosal atrophy， and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue， as well as 5-HT3R， SP， and AChE in hypothalamic tissue， were significantly decreased （P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced （P<0.01）. Compared with the model group， all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate （P<0.01）. The glands in the gastric antrum were more regularly arranged， with no inflammatory cell infiltration observed. Serum levels of 5-HT， SP， ACh， and TPH were significantly increased （P<0.01）. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue and 5-HT3R， SP， and AChE in hypothalamic tissue were significantly upregulated （P<0.05， P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was significantly increased （P<0.01）. ConclusionYueju Wan has preventive and therapeutic effects on FD， and its mechanism may be related to regulation of the 5-HT signaling pathway， promotion of brain-gut peptide secretion， and enhancement of gastric motility.

The surgical management of gastroesophageal reflux disease has evolved significantly with the increased understanding of the physiology of the reflux barrier. Initially, emphasis was on reduction of hiatal hernias and crural closure. With persistence of reflux symptoms, along with the development of esophageal manometry and the discovery of a high-pressure zone, focus evolved to surgical augmentation of the lower esophageal sphincter, including reconstruction of the angle of His, ensuring sufficient intra-abdominal esophageal length, fundoplication, and magnetic sphincter augmentation. More recently, the role of crural closure in antireflux and hiatal hernia repair has again received renewed attention due to the persistence of postoperative complications and recurrences. Rather than simply preventing transthoracic herniation of the fundoplication as was originally thought, crural closure has been documented to have a critical role in re-establishing intra-abdominal esophageal length and maintaining the pressure of LES. The application of mesh provides more options for strengthening crural closure. In this review, this article will discuss the evolution of surgical techniques for gastroesophageal reflux disease over the past century, aiming to better guide the surgical treatment and clinical research of gastroesophageal reflux disease.

Gallbladder polypoid lesions (GPLs) refer to any elevated lesion of the mucosal surface of the gallbladder wall, and the prevalence is estimated to be between 0.9% and 12.1%. GPLs include benign polyps and malignant polyps. Benign polyps are further classified as non-neoplastic polyps and neoplastic polyps. Cholesterol polyps are the most common benign polyps and adenocarcinoma is the main type of malignant polyp. Hepatitis B virus infection, liver function abnormalities, dyslipidemia, and obesity are the main risk factors for GPLs. Studies of biological mechanisms have focused on malignant gallbladder polyps, the development of which is regulated by hormone levels in vivo, gut microbiota, inflammation, oxidative stress, Salmonella typhimurium, and related molecules. Diagnostic modalities include chemical examination and imaging examination, with imaging examination currently being the mainstay. Treatment of patients with GPLs is based on the presence or absence of symptoms, age, size of the polyps, tendency of the polyp to increase, and risk factors for symptomatic malignancy to determine whether surgery should be performed.

Objective: To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals. Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets. Results: The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%. Conclusion Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.

Objective:To explore the association between short-term exposures to fine particulate matter (PM 2.5) on blood lipids in the elderly. Methods:In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM 2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM 2.5 exposure at different lag with blood lipids and dyslipidemia. Results:The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m 2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 μg/m 3 increase in PM 2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95% CI: 1.22%-2.32%), 1.90% (95% CI: 1.18%-2.63%), 1.99% (95% CI: 1.37%-2.60%) and 1.74% (95% CI: 1.11%-2.37%), and the OR values (95% CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion:There is a significant association of short-term PM 2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

Objective:To explore the association between short-term exposures to fine particulate matter (PM 2.5) on blood lipids in the elderly. Methods:In this panel study, five repeated measurements were performed on 76 people aged 60-69 in Jinan city. Each participant had a PM 2.5 monitor for 72 hours before each health examination, including a questionnaire survey, physical examination, and biological sample collection. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were examined, and non-HDL-C concentrations were calculated by subtracting HDL-C from TC. The generalized linear mixed-effects model was used to quantify the association of personal PM 2.5 exposure at different lag with blood lipids and dyslipidemia. Results:The age of 70 participants was (65.0±2.8) years, of which 48.6% (34/70) were males. The BMI of participants was (25.0±2.5) kg/m 2. Their TC, TG, LDL-C, HDL-C, and non-HDL-C concentrations were (5.75±1.32), (1.55±0.53), (3.27±0.94), (1.78±0.52), and (3.97±1.06) mmol/L, respectively. Generalized linear mixed-effects model showed that after adjusting for confounding factors, at lag 72 hours, each 10 μg/m 3 increase in PM 2.5 was associated with the percentage change in TC, LDL-C, HDL-C and non-HDL-C about 1.77% (95% CI: 1.22%-2.32%), 1.90% (95% CI: 1.18%-2.63%), 1.99% (95% CI: 1.37%-2.60%) and 1.74% (95% CI: 1.11%-2.37%), and the OR values (95% CI) of hypercholesterolemia, hypertriglyceridemia and hyperbetalipoproteinemia were 1.11 (1.01-1.22), 1.33 (1.03-1.71) and 1.15 (1.01-1.31), respectively. Conclusion:There is a significant association of short-term PM 2.5 exposure with the concentration of blood lipids and the risk of dyslipidemia in the elderly.

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.
Child ; DNA Copy Number Variations ; Female ; Genetic Testing ; Genetics, Medical ; Genome, Human/genetics* ; Genomics ; Humans ; Pregnancy ; United States

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies

Objective:To investigate the safety and efficacy of individualized sunitinib schedule for patients with metastatic renal cell carcinoma (mRCC) according to the monitoring results of plasma drug concentration.Methods:The clinical data of patients with mRCC who received sunitinib treatment in our center from January 2014 to December 2020 were retrospectively analyzed, including 20 patients who underwent monitoring of plasma drug concentration (monitoring group), and 45 patients, matched by propensity score matching, received sunitinib but did not undergo monitoring of plasma drug concentration during the same period (unmonitored group). In the monitoring group, there were 12 males and 8 females. The mean age was 52.9 years, and ECOG score ≤1 in 16 cases (80%). Three patients were in the IMDC favorable-risk group, 15 patients were in the intermediate-risk group, and 2 patients were in the high-risk group. There were 18 cases of clear cell carcinoma and 2 cases of non-clear cell carcinoma, 5 cases of ISUP grade 1-2 and 11 cases of grade 3-4. In the unmonitored group, there were 31 males and 14 females. The mean age was 57.7 years, and 30 patients had ECOG score ≤1, 15 cases ≥2. There were 10 cases in IMDC favorable-risk group, 23 cases in intermediate-risk group, and 12 cases in high-risk group. Thirty-seven cases were clear cell carcinoma and 8 cases were non-clear cell carcinoma, 8 cases were in ISUP grade 1-2 and 28 cases in grade 3-4. There were no statistically significant differences between the two groups in the above parameters ( P>0.05). The monitoring group used the regimen of taking sunitinib for 4 weeks and stopping for 2 weeks (4/2 week) in the first cycle. The blood concentration of sunitinib was monitored before the first cycle and on days 4, 7, 10, 14, 21 and 28, and personalized medication plan was formulated according to the curve of the blood concentration. The 4/2 week scheme was adopted in the undetected monitoring group.The two groups were compared in the incidence of adverse events (AEs), progression-free survival (PFS), overall survival (OS), tumor treatment response and other clinical outcomes. Results:In the monitoring group, 90% (18/20) of patients receiving sunitinib had a steady-state plasma concentration of more than 150ng/ml, of which 10 patients (50%) had a plasma concentration of 150-200 ng/ml and 8 patients (40%) had a plasma concentration of more than 200 ng/ml. Meanwhile, all patients with plasma concentration higher than 150 ng/ml developed severe AEs (grade 3 and above) after treatment. The other two patients' plasma concentration were 100-150 ng/ml, and did not have severe AEs.All patients in the monitoring group received individualized medication schedule adjustment according to the plasma drug concentration and the occurrence point of severe AEs, ensuring that the peak plasma drug concentration was maintained at about 100-150 ng/ml. Among them, 6 patients were changed to take 2 weeks and stop for 1 week (2/1 week schedule), 4 patients were changed to take 10 days and stop for 5 days (10/5 d schedule), 7 patients were changed to take 7 days and stop for 3 days (7/3 d schedule), and 3 patients were changed to take 5 days and stop for 2 days (5/2 d schedule). The incidence of severe AEs significantly decreased from 90% (18/20) to 35% (7/20), and the difference was statistically significant ( P=0.003), while the incidence of grade 3 and higher AEs was 55.6% (25/45) in the standard group, which was statistically significant compared with the incidence of severe AEs before adjustment in the monitoring group ( P=0.006). Further analysis of the efficacy difference between the two groups showed that the overall objective response rate in the monitoring group (40%, 8/20) was higher than that in the standard group (20%, 9/45), although the difference was not statistically significant ( P=0.09). Median PFS and OS were significantly longer in the monitored group than in the standard group (PFS: 23 vs. 10 months, P=0.002; OS: not reached vs.25 months, P=0.005). Conclusions:The bioavailability of sunitinib is high in mRCC patients, which may lead to higher plasma drug concentration, adjustment of medication regimen based on blood concentration monitoring significantly improved patient safety and clinical outcomes. However, further validation by larger-scale, multi-center and prospective studies is needed.