A serum metabolomics study of vascular cognitive impairment patients based on Traditional Chinese medicine syndrome differentiation.

Objective: Vascular cognitive impairment (VCI) accounts for approximately 50%-70% of all dementia cases and poses a significant burden on existing medical systems. Identifying an optimal strategy for preventing VCI and developing efficient symptomatic treatments remains a significant challenge. Syndrome differentiation represents a fundamental approach for personalized diagnosis and treatment in Traditional Chinese Medicine (TCM) and aligns with the principles of precision medicine. The objective of this study was to elucidate the metabolic characteristics of VCI based on TCM syndrome differentiation, thus providing novel insights into the diagnosis and treatment of VCI. Methods: A 2-year cross-sectional cognitive survey was conducted in four communities in Beijing between September 2020 and November 2022. The syndrome differentiation of participants was based on the Kidney-Yang Deficiency Syndrome Scale (KYDSS), which was originally developed by Delphi expert consultation. The identification of serum metabolites was performed by Ultra performance liquid chromatography (UPLC) analysis coupled with an electrospray ionization quadruple time-of-flight mass spectrometer (ESI-QTOF MS). Multivariate, univariate, and pathway analyses were used to investigate metabolic changes. Logistic regression models were also used to construct metabolite panels that were capable of discerning distinct groups. Phospholipase A2 (PLA2) levels were measured by a commercial ELISA kit. Results: A total of 2,337 residents completed the survey, and the prevalence of VCI was 9.84%. Of the patients with VCI, those with Kidney-Yang deficiency syndrome (VCIS) accounted for 70.87% of cases and exhibited more severe cognitive impairments. A total of 80 participants were included in metabolomics study, including 30 with VCIS, 20 without Kidney-Yang deficiency syndrome (VCINS), and 30 healthy control participants (C). Ultimately, 45 differential metabolites were identified when comparing the VCIS group with group C, 65 differential metabolites between the VCINS group and group C, and 27 differential metabolites between the VCIS group and the VCINS group. The downregulation of phosphatidylethanolamine (PE), and phosphatidylcholine (PC) along with the upregulation of lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), phosphatidic acid (PA) and phospholipase A2 (PLA2) can be considered as the general metabolic characteristics associated with VCI. Dysfunction of glycerophospholipids, particularly LPEs and PCs, was identified as a key metabolic characteristic of VCIS. In particular Glycerophospho-N-Arachidonoyl Ethanolamine (GP-NArE) was discovered for the first time in VCI patients and is considered to represent a potential biomarker for VCIS. The upregulation of PLA2 expression was implicated in the induction of alterations in glycerophospholipid metabolism in both VCIS and VCINS. Moreover, robust diagnostic models were established based on these metabolites, achieving high AUC values of 0.9322, 0.9550, and 0.9450, respectively. Conclusion: These findings contribute valuable information relating to the intricate relationship between metabolic disorders in VCI, neurodegeneration and vascular/neuroinflammation. Our findings also provide a TCM perspective for the precise diagnosis and treatment of VCI in the context of precision medicine.

Celastrol inhibits migration, proliferation and transforming growth factor-ß2-induced epithelial-mesenchymal transition in lens epithelial cells.

AIM: To investigate the mechanism of celastrol in inhibiting lens epithelial cells (LECs) fibrosis, which is the pathological basis of cataract. METHODS: Human LEC line SRA01/04 was treated with celastrol and transforming growth factor-ß2 (TGF-ß2). Wound-healing assay, proliferation assay, flow cytometry, real-time polymerase chain reaction (PCR), Western blot and immunocytochemical staining were used to detect the pathological changes of celastrol on LECs. Then, we cultured Sprague-Dawley rat lens in medium as a semi-in vivo model to find the function of celastrol further. RESULTS: We found that celastrol inhibited the migration of LECs, as well as proliferation (P<0.05). In addition, it induced the G2/M phase arrest by cell cycle-related proteins (P<0.01). Moreover, celastrol inhibited epithelial-mesenchymal transition (EMT) by the blockade of TGF-ß/Smad and Jagged/Notch signaling pathways. CONCLUSION: Our study demonstrates that celastrol could inhibit TGF-ß2-induced lens fibrosis and raises the possibility that celastrol could be a potential novel drug in prevention and treatment of fibrotic cataract.

Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis.

OBJECTIVE: To treat patients with vascular mild cognitive impairment (VMCI) using traditional Chinese medicine (TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis (LTA). METHOD: A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules. RESULTS: Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types. CONCLUSION: A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.

A data-driven method for syndrome type identification and classification in traditional Chinese medicine.

The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.

[Balloon dilation with gastroscope for esophageal stricture in children].

OBJECTIVE: To evaluate the efficacy and safety of balloon dilation (BD) with gastroscope in treatment of esophageal stricture in children. METHODS: BD was performed in 12 children aged 5 - 59 months, average age 26 months, course of disease was 2 - 26 months, with esophageal stricture, 7 cases with anastomotic strictures secondary to surgical repair of esophageal atresia, 3 with congenital esophageal stenosis, 2 with corrosive esophageal strictures. All procedures were performed under tracheal intubation and intravenous anesthesia using the 3rd grade controlled radial expansion (CRE) esophagus-balloon with gastroscope. Firstly the balloon was inserted into the esophagus through mouth, then put in the gastroscope. Under the direct guidance of gastroscope the balloon was positioned across the stricture, then the balloon was filled with saline to get needed pressure and maintained for 3 minutes. The procedure was repeated 3 times at an interval of 3 minutes. The abdominal pain, melena and vomiting were observed, as well as the diet taken thereafter, the size of the stricture and the nutrition status were observed for 3 to 12 months after the dilation. RESULTS: Twenty-two dilations were performed in 12 cases, 19 succeeded, 3 cases developed complication during the dilation, the total success rate was 86%. The procedure failed in 3 cases and succeeded in 9 cases, the effective rate was 75%. Follow-up and repeated gastroscopy were performed within 3 to 12 months after the dilation, the diameter of the stricture was 9-13 mm, compared with 2-8 mm before the dilation. Eight of the children could take solid food and nutritional status was improved. CONCLUSIONS: BD with the 3rd grade CRE esophagus-balloon under gastroscopy is a simple and effective method to treat esophagus stricture in children, especially for anastomotic strictures secondary to surgical repair of esophageal atresia.

[Genotypic study on the Helicobacter pylori vacA, cagA and iceA genes in the infected children in Guangzhou area].

OBJECTIVE: To investigative vacA, cagA and iceA genes dominant genotypes of Helicobacter pylori (Hp) isolated from children suffering from gastric and duodenal diseases in Guangzhou area. METHODS: Totally 105 children who underwent gastroscopy in Guangzhou Children's Hospital were enrolled into this study. From each patient, 3 biopsy specimens from the gastric antrum were taken, one was used for rapid urease test, one for histological examination, and one for polymerase chain reaction (PCR) for detecting ureA, vacA, cagA, and iceA genes. DNA was prepared directly from the biopsy specimens from the gastric antrum using a QIAamp DNA mini kit (Qiagen, Germany) according to the manufacturer's instructions. Then 11 primers were used for detecting the genotypes including ureas, (s1, s1a, s1b, s1c, s2) and m (m1, m1T, m2) region of vacA, cagA and iceA (iceA1 and iceA2) genotypes in the 105 children. The distribution of the genotypes of Hp was analyzed. RESULT: Among the 105 children, only 52 children were positive by the three methods, among these 52 children, 26 were boys and 26 girls. Hp vacA s1as1c/m2 was detected in 43 out of 52 children (82.7%), s1as1c/m1T in 9.6% (5/52), m region that could not betyped was 7.7% (4/52). No strains presented genotypes vacA s1b, s2, m1. The comparison of the positive ratio of vacA s1as1 c/m2 detected in the children infected with Hp and that of the other combination of signal region and middle region was statistically significantly different (P < 0.01). With regard to cagA gene, cagA(+) gene and cagA(-) gene were found in 90.4% (47/52) and 9.6% (5/52) of the children, respectively. The cagA(+) gene was more frequent in the children infected with Hp. Single iceA1 was detected in 78.8% (41/52) children, and single iceA2 was detected to be 1.9% (1/52), multiple strains infection of iceA1 and iceA2 were detected in 3.8% (2/52) children, iceA1 and iceA2 were not detected in 15.4% (8/52), the comparison of the positive ratio of iceA1 detected in the children infected with Hp and that of the other genotypes was statistically significantly different (P < 0.01). CONCLUSION: The s1as1c/m2, cagA and iceA1 were the dominant genotypes of Hp in the children in Guangzhou area and s1as1c/m2, cagA and iceA1 were the dominant genotypes combination of Hp in the children in this area.