To explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet.

Investigator-initiated clinical trials （IIT） are an important part of scientific and technological activities involving human study participants. Among them， high-quality IIT can be used to support the marketing and registration application of drugs， medical devices， and other products when conditions permit. Currently， there is a huge gap between IIT and industry-initiated clinical trials. The use of unlisted products in IIT has problems， such as lack of regulatory support， insufficient research funding support， the need to improve the ability of clinical research management departments， the weakness of professional clinical research teams， and the difficulty of ethics review to match the demands. The challenges could be addressed by improving regulations and conducting pilot trials on a small scale， guaranteeing adequate research funding， strengthening the construction of clinical research management systems， building professional clinical research teams， ensuring the quality of ethical reviews and strict follow-up reviews， shifting from ethical reviews to a system for protecting research participants， and reinforcing training for researchers. Ethics committees should strictly review key points， such as the risk-benefit ratio， informed consent， research funding， compensation for damages， qualifications and equipment of research team members， and management of conflict of interest.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.

Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.

Alzheimer's disease (AD) is the leading cause of dementia, and no effective treatment has been developed for it thus far. Recently, the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions. Accordingly, the potential therapeutic effect of pterostilbene (PTS) on AD has been demonstrated in multiple in vivo and in vitro experiments. In this study, we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD. Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation. Moreover, PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha (PPAR-α), monoamine oxidase B (MAO-B), silent information regulator sirtuin 1 (SIRT1), and phosphodiesterase 4A (PDE4A). Furthermore, to further elucidate the potential therapeutic mechanisms of PTS in AD, we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins, and the obtained binding energies ranged from -2.83 to -5.14 kJ/mol, indicating that these proteins exhibit good binding ability with PTS. Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD. In summary, by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD, it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD, either using PTS or other developed drug interventions.

Screening carbonyl reductases with the ability to catalyze the reduction of complex carbonyl compounds is of great significance for the biosynthesis of R-tolvaptan(R-TVP). In this study, the target carbonyl reductase in the crude enzyme extract of rabbit liver was separated, purified, and identified by ammonium sulfate precipitation, gel-filtration chromatography, ion exchange chromatography, affinity chromatography, and protein mass spectrometry. With the rabbit liver genome as the template, the gene encoding the carbonyl reductase rlsr5 was amplified by PCR and the recombinant strain was successfully constructed. After RLSR5 was purified by affinity chromatography, its enzymatic properties were characterized. The results indicated that the gene sequence of rlsr5 was 972 bp, encoding a protein with a molecular weight of 40 kDa. RLSR5 was a dimeric protein, and each monomer was composed of a (α/β)₈-barrel structure. RLSR5 could asymmetrically reduce 7-chloro-1-[2-methyl-4-[(2- methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (prochiral ketone, PK) to synthesize R-TVP. The specific activity of the enzyme was 36.64 U/mg, and the optical purity of the product was 99%. This enzyme showcased the optimal performance at pH 6.0 and 30 °C. It was independent of metal ions, with the activity enhanced by Mn²⁺. This study lays a foundation for the biosynthesis of tolvaptan of optical grade.
Animals ; Rabbits ; Alcohol Oxidoreductases/biosynthesis* ; Recombinant Proteins/metabolism* ; Escherichia coli/metabolism* ; Liver/enzymology*

Adverse drug reactions (ADRs) significantly impact clinical medication safety. The timely identification and prediction of ADRs rely on the efficient analysis of real-world data, such as electronic health records, social media, and spontaneous reporting databases. In recent years, the rapid advancement of artificial intelligence, particularly large language models, in natural language processing, causal reasoning, and complex data mining has provided new technological means for real-time ADRs monitoring and individualized prediction. This paper summarizes the latest research achievements in AI-driven ADRs monitoring. Focusing on diverse data sources, including structured databases and electronic health records, it elaborates on the advantages andchallenges of AI in ADRs event extraction, relationship identification, causal analysis, and risk prediction. The aim is to provide a theoretical reference for constructing more intelligent and efficient ADRs monitoring systems.

Objective:To analyze the effect and safety of tirofiban bridging combined with aspirin for anti-platelet therapy in patients with acute cerebral infarction (ACI) beyond the thrombolytic time window.Methods:Sixty patients with ACI treated in Beijing Royal Hospital from January 2021 to September 2022 were retrospectively analyzed. Among them, 30 cases were treated with tirofiban bridging aspirin as the observation group, while 30 cases were treated with aspirin alone as the control group. The total effective rate of clinical treatment, the degree of neurological deficit, the degree of disease outcome and the incidence of adverse reactions were compared between the two groups. The degree of neurological deficit was evaluated using the National Institutes of Health stroke scale (NIHSS), and the degree of disease outcome was evaluated using the modified Rankin scale (mRS).Results:The overall effective rate in the observation group was significantly higher than that in the control group: 93.3% (28/30) vs. 66.7% (20/30), with a statistically significant difference ( χ2 = 10.97, P<0.01). Before treatment, there was no statistically significant difference in NIHSS score between the two groups ( P>0.05). However, after treatment, the NIHSS score in the observation group was significantly lower than that in the control group: (2.83 ± 1.87) scores vs. (4.93 ± 3.05) scores, indicating a significant difference ( t = -3.21, P = 0.002). No significant difference was observed in mRS score between the two groups before treatment( P>0.05). After treatment, the observation group showed significantly lower mRS score compared to the control group: 2.00 (1.00, 2.00) scores vs. 3.00 (2.00, 4.00) scores ( P = 0.006). There was no statistical difference in the incidence of adverse reactions between the observation group and control groups ( P>0.05). Conclusions:Tirofiban bridging aspirin has stronger inhibitory effect on platelet activity than simple application of aspirin for ACI patients with ultra-thrombolytic window, which can rapidly improve the degree of neurological impairment and daily living ability of patients, and the incidence of adverse reactions has not increased significantly.

Objective:To compare the efficacy and safety of cold-endoscopic mucosal resection (C-EMR) and hot-endoscopic mucosal resection (H-EMR) for the treatment of colorectal polyps sized 10-20mm.Methods:Patients who underwent colonoscopy at the Gastrointestinal Endoscopy Center of the Eighth Affiliated Hospital, Sun Yat-sen University from January 2022 to January 2023 were selected as the research subjects. Patients meeting the inclusion criteria with at least one 10-20 mm, Paris type Ⅰs, type Ⅱa polyp were selected. They were divided into C-EMR group (no high-frequency current treatment) and H-EMR group (high-frequency electrical polyp removal) based on the random number table method. The main outcome measures were the complete resection rate of polyps, the incidence of postoperative complications (bleeding, perforation and infection), and the recurrence rate of polyps in the two groups. Secondary outcomes were the procedure time and cost-effectiveness.Results:A total of 209 eligible polyps were found in 209 patients, 105 in the C-EMR group (105 patients) and 104 in the H-EMR group (104 patients). There was no significant difference in the complete removal rate of polyps [91.4% (96/105) VS 95.2% (99/104), χ2=1.184, P=0.276], the recurrence rate of polyps [2.9% (3/105) VS 1.9% (2/104), χ2=0.195, P=0.683] or the incidence of complications [5.7% (6/105) VS 1.9% (2/104), χ2=2.040, P=0.280] between the C-EMR group and the H-EMR group. Compared with H-EMR group, the operation time of C-EMR group was shorter (5.26±2.41 min VS 9.34±5.63 min, t=-8.478, P<0.001), and the number of titanium clips used was fewer (2.55±0.94 VS 3.94±1.14, t=-9.623, P<0.001), and the differences between the two groups were statistically significant. The cost of polypectomy was lower in the C-EMR group than that in the H-EMR group (2 720±452 yuan VS 3 031±293 yuan), but the difference was not stastistically significant（ t=-5.896， P=0.651）. Conclusion:C-EMR demonstrates non-inferior efficacy and safety in treating 10-20 mm colorectal polyps compared with H-EMR. Widespread adoption of C-EMR may lead to reduced healthcare costs and expenditures.