OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC). METHODS: A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05). CONCLUSION Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans ; Acupuncture Points ; Gastroesophageal Reflux/physiopathology* ; Male ; Female ; Cough/physiopathology* ; Middle Aged ; Aged ; Acupuncture Therapy ; Adult ; Treatment Outcome ; Lung/physiopathology* ; Meridians

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

The effect of Huanglian Jiedu Decoction on the intestinal flora of type 2 diabetes mellitus(T2DM) was investigated using 16S rRNA sequencing technology. Sixty rats were randomly divided into a normal group(10 rats) and a modeling group(50 rats). After one week of adaptive feeding, a high-fat diet + streptozotocin was given for modeling, and fasting blood glucose >16.7 mmol·L~(-1) was considered a sign of successful modeling. The modeling group was randomly divided into the model group, high-, medium-, and low-dose groups of Huanglian Jiedu Decoction, and metformin group. After seven days of intragastric treatment, the feces, colon, and pancreatic tissue of each group of rats were collected, and the pathological changes of the colon and pancreatic tissue of each group were observed by hematoxylin-eosin staining. The changes in the intestinal flora structure of each group were observed by the 16S rRNA sequencing method. The results showed that compared with the model group, the high-, medium-, and low-dose of Huanglian Jiedu Decoction reduced fasting blood glucose levels to different degrees and showed no significant changes in body weight. The number of islet cells increased, and intestinal mucosal damage attenuated. Alpha diversity analysis revealed that Huanglian Jiedu Decoction reduced the abundance and diversity of intestinal flora in rats with T2DM; at the phylum level, low-and mediam-dose of Huanglian Jiedu Decoction reduced the abundance of Bacteroidota, Proteobacteria, and Desulfobacterota and increased the abundance of Firmicute and Bacteroidota/Firmicutes, while the high-dose of Huanglian Jiedu Decoction increased the relative abundance of Proteobacteria and Bacteroidota/Firmicutes ratio, and decreaseal the relative; abundance of Firmicute; at the genus level, Huanglian Jiedu Decoction increased the relative abundance of Allobaculum, Blautia, and Lactobacillus; LEfse analysis revealed that the biomarker of low-and medium-dose groups of Huanglian Jiedu Decoction was Lactobacillus, and the structure of the intestinal flora of the low-dose group of Huanglian Jiedu Decoction was highly similar to that of the metformin group. PICRUSt2 function prediction revealed that Huanglian Jiedu Decoction mainly affected carbohydrate and amino acid metabolic pathways. It suggested that Huanglian Jiedu Decoction could reduce fasting blood glucose and increase the number of islet cells in rats with T2DM, and its mechanism of action may be related to increasing the abundance of short-chain fatty acid-producing strains and Lactobacillus and affecting carbohydrate and amino acid metabolic pathways.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Bacteria/drug effects* ; Blood Glucose/metabolism*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Purpose: To characterize the patterns of demographic data, dermatologic diagnosis, and disposition regarding pediatric dermatological presentations in an emergency department (ED) at Armadale Health Service, a secondary outer metropolitan hospital in Perth, Western Australia. Methods: Retrospective cross-sectional study auditing pediatric dermatological presentations to the ED from December 2022 through November 2023. We analyzed the age group, sex, dermatologic diagnosis, Australasian Triage Scale, ED length of stay, and disposition. The age group comprised infants, preschoolers, schoolers, and adolescents. The diagnosis included anaphylaxis and angioneurotic edema (AAE), allergy-related and urticarial dermatitis (AUD), eczema and other dermatitis (EOD), infective dermatoses, and not elsewhere classified. Results: Of the 540 pediatric patients who presented to the ED with a dermatological complaint, 44.4% were girls with a median age of 4.5 years (interquartile range, 1.5-9.3) and a hospitalization rate of 7.6%. The dermatologic diagnoses consisted of AUD (34.3%), infective dermatoses (29.3%), EOD (23.3%), AAE (8.5%), and not elsewhere classified (4.6%). Most patients were triaged as an Australasian Triage Scale category 3-4, with a median ED length of stay of 2.3 hours (1.5-3.5 hours). Pairwise comparisons showed differences in the diagnoses between infants and preschoolers and between schoolers and adolescents for EOD and infective dermatoses (P < 0.001). The hospitalized patients showed a higher proportion of AAE, EOD, and infective dermatoses than those discharged (P < 0.001). Patients with AUD were hospitalized less (odds ratio, 0.06; 95% confidence interval, 0.12-0.30; compared with AAE). No dermatological emergencies, such as Stevens-Johnson syndrome, were identified. Conclusion Our findings underscore regional differences and support global efforts to reduce non-life-threatening pediatric dermatological presentations to the ED. This study may contribute to the ongoing discourse on effectively managing such presentations in EDs.

Purpose: To characterize the patterns of demographic data, dermatologic diagnosis, and disposition regarding pediatric dermatological presentations in an emergency department (ED) at Armadale Health Service, a secondary outer metropolitan hospital in Perth, Western Australia. Methods: Retrospective cross-sectional study auditing pediatric dermatological presentations to the ED from December 2022 through November 2023. We analyzed the age group, sex, dermatologic diagnosis, Australasian Triage Scale, ED length of stay, and disposition. The age group comprised infants, preschoolers, schoolers, and adolescents. The diagnosis included anaphylaxis and angioneurotic edema (AAE), allergy-related and urticarial dermatitis (AUD), eczema and other dermatitis (EOD), infective dermatoses, and not elsewhere classified. Results: Of the 540 pediatric patients who presented to the ED with a dermatological complaint, 44.4% were girls with a median age of 4.5 years (interquartile range, 1.5-9.3) and a hospitalization rate of 7.6%. The dermatologic diagnoses consisted of AUD (34.3%), infective dermatoses (29.3%), EOD (23.3%), AAE (8.5%), and not elsewhere classified (4.6%). Most patients were triaged as an Australasian Triage Scale category 3-4, with a median ED length of stay of 2.3 hours (1.5-3.5 hours). Pairwise comparisons showed differences in the diagnoses between infants and preschoolers and between schoolers and adolescents for EOD and infective dermatoses (P < 0.001). The hospitalized patients showed a higher proportion of AAE, EOD, and infective dermatoses than those discharged (P < 0.001). Patients with AUD were hospitalized less (odds ratio, 0.06; 95% confidence interval, 0.12-0.30; compared with AAE). No dermatological emergencies, such as Stevens-Johnson syndrome, were identified. Conclusion Our findings underscore regional differences and support global efforts to reduce non-life-threatening pediatric dermatological presentations to the ED. This study may contribute to the ongoing discourse on effectively managing such presentations in EDs.

Purpose: To characterize the patterns of demographic data, dermatologic diagnosis, and disposition regarding pediatric dermatological presentations in an emergency department (ED) at Armadale Health Service, a secondary outer metropolitan hospital in Perth, Western Australia. Methods: Retrospective cross-sectional study auditing pediatric dermatological presentations to the ED from December 2022 through November 2023. We analyzed the age group, sex, dermatologic diagnosis, Australasian Triage Scale, ED length of stay, and disposition. The age group comprised infants, preschoolers, schoolers, and adolescents. The diagnosis included anaphylaxis and angioneurotic edema (AAE), allergy-related and urticarial dermatitis (AUD), eczema and other dermatitis (EOD), infective dermatoses, and not elsewhere classified. Results: Of the 540 pediatric patients who presented to the ED with a dermatological complaint, 44.4% were girls with a median age of 4.5 years (interquartile range, 1.5-9.3) and a hospitalization rate of 7.6%. The dermatologic diagnoses consisted of AUD (34.3%), infective dermatoses (29.3%), EOD (23.3%), AAE (8.5%), and not elsewhere classified (4.6%). Most patients were triaged as an Australasian Triage Scale category 3-4, with a median ED length of stay of 2.3 hours (1.5-3.5 hours). Pairwise comparisons showed differences in the diagnoses between infants and preschoolers and between schoolers and adolescents for EOD and infective dermatoses (P < 0.001). The hospitalized patients showed a higher proportion of AAE, EOD, and infective dermatoses than those discharged (P < 0.001). Patients with AUD were hospitalized less (odds ratio, 0.06; 95% confidence interval, 0.12-0.30; compared with AAE). No dermatological emergencies, such as Stevens-Johnson syndrome, were identified. Conclusion Our findings underscore regional differences and support global efforts to reduce non-life-threatening pediatric dermatological presentations to the ED. This study may contribute to the ongoing discourse on effectively managing such presentations in EDs.