Understanding the Relationship Between Vascular Smooth Muscle Cell Function and the Efficacy of Acupuncture in Treating Cerebral Ischemic Stroke: A Preclinical Meta-Analysis and Systematic Review.

Background: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models. Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD). Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=-3.75 [95% CI, -5.54 to -1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies. Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.

Association between threat-related adverse childhood experiences and chronic lung diseases in a middle and older aged population: A cross-sectional and longitudinal study in China.

OBJECTIVES: We investigated the association between threat-related adverse childhood experiences (ACEs) and the risk of chronic lung diseases (CLDs). METHODS: The data used for this study were extracted from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey of respondents recruited from 450 villages/urban communities in 28 provinces. Threat-related ACEs were constructed using five adverse factors: household substance abuse, physical abuse, domestic violence, unsafe neighbourhood, and bullying). Participants were divided into three groups according to their number of threat-related ACEs at baseline and at follow-up. The association between threat-related ACEs and CLD prevalence in the cross-sectional study was calculated using logistic regression models. The association between threat-related ACEs and CLD onset was evaluated using Cox proportional regression models in the cohort study. Potential confounders were considered in both the cross-sectional and cohort studies. RESULTS: The CLD prevalence in the total population, no exposure group, exposure to one threat-related ACE, and exposure to at least two threat-related ACEs were 10.07% (1320/13104), 9.20% (665/7232), 10.89% (421/3865), and 11.66% (234/2007), respectively. Exposure to one threat-related ACE (OR: 1.23, 95% CI: 1.07-1.41) and exposure to at least two threat-related ACEs (OR: 1.31, 95% CI: 1.11-1.55) were significantly associated with higher CLD prevalence rates. The cohort study included 11,645 participants. During the 7-year follow-up, 738 CLD incidents were identified. Similarly, exposure to one threat-related ACE (HR: 1.20, 95% CI: 1.01-1.43) and at least two threat-related ACEs (HR: 1.64, 95% CI: 1.35-2.00) were significantly associated with a higher CLD incidence risk. CONCLUSIONS: Exposure to threat-related ACEs was significantly associated with a higher CLD prevalence risk and onset. It is crucial to identify individuals who have encountered childhood threats and prioritise the monitoring of their pulmonary function.

Effect of acupuncture timing on functional impairment at 6 months post-onset in patients with first-ever stroke: a prospective cohort study. / é’ˆåˆºæ—¶æœºå¯¹é¦–æ¬¡ä¸­é£Žæ‚£è€ å‘ç— åŽ6ä¸ªæœˆåŠŸèƒ½éšœç¢çš„å½±å“ï¼šå‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To observe the effect of acupuncture intervention in the acute phase on functional impairment at 6 months post-onset in patients with first-ever stroke, and provide evidence for selecting optimal acupuncture timing in the real-world setting. METHODS: A total of 601 patients with first-ever stroke were divided into an acute intervention group (onset within 14 days, 256 cases) and a non-acute intervention group (onset between 15 and 90 days, 345 cases) based on whether they received acupuncture treatment in the acute phase. The assessments were conducted at baseline and 6 months post-onset, including modified Rankin scale (mRS) score, total number of acupuncture sessions, total number of combined therapies (moxibustion, cupping, tuina and rehabilitation treatment), recurrence, death events and disability. Logistic regression analysis was used to analyze the association between acupuncture timing and the risk of disability at 6 months post-onset. The mRS transition method was employed to assess the effect of acupuncture timing on functional improvement at 6 months post-onset. RESULTS: Without adjusting for confounding factors, compared with the non-acute intervention group, the patients in the acute intervention group had reduced risk of disability at 6 months post-onset (OR=0.434, 95%CI: 0.309-0.609, P=0.000). After adjusting for variables i.e. severity of illness, number of acupuncture sessions, and number of cupping sessions, compared with the non-acute intervention group, the patients in the acute intervention group had reduced risk of disability at 6 months post-onset (OR=0.588, 95%CI: 0.388-0.890, P=0.012). After adjusting for all confounding factors, including severity of illness, number of acupuncture sessions, number of cupping sessions, gender, smoking and drinking history, comorbidities, and diagnosis, compared with the non-acute intervention group, the patients in the acute intervention group continued to have a reduced risk of disability at 6 months post-onset (OR=0.629, 95%CI: 0.408-0.971, P=0.036). Both groups showed an overall shift towards lower mRS scores at 6 months post-onset compared to baseline, with a more significant shift towards lower scores in the acute intervention group than the non-acute intervention group. CONCLUSIONS: In the real-world setting, acupuncture intervention in the acute phase in patients with first-ever stroke, compared to acupuncture intervention after the acute phase, reduces the risk of disability at 6 months post-onset and improves functional status.

Application research of radiomics in colorectal cancer: A bibliometric study.

BACKGROUND: Radiomics has shown great potential in the clinical field of colorectal cancer (CRC). However, few bibliometric studies have systematically analyzed existing research in this field. The purpose of this study is to understand the current research status and future development directions of CRC. METHODS: Search the English documents on the application of radiomics in the field of CRC research included in the Web of Science Core Collection from its establishment to October 2023. VOSviewer and CiteSpace software were used to conduct bibliometric and visual analysis of online publications related to countries/regions, authors, journals, references, and keywords in this field. RESULTS: A total of 735 relevant documents published from Web of Science Core Collection to October 2023 were retrieved, and a total of 419 documents were obtained based on the screening criteria, including 376 articles and 43 reviews. The number of publications is increasing year by year. Among them, China publishes the most relevant documents (n = 238), which is much higher than Italy (n = 69) and the United States (n = 63). Tian Jie is the author with the most publications and citations (n = 17, citations = 2128), GE Healthcare is the most productive institution (n = 26), Frontiers in Oncology is the journal with the most publications (n = 60), and European Radiology is the most cited journal (n = 776). Hot spots for the application of radiomics in CRC include magnetic resonance, neoadjuvant chemoradiotherapy, survival, texture analysis, and machine learning. These directions are the current hot spots for the application of radiomics research in CRC and may be the direction of continued development in the future. CONCLUSION: Through bibliometric analysis, the application of radiomics in CRC has been increasing year by year. The application of radiomics improves the accuracy of preoperative diagnosis, prediction, and prognosis of CRC. The results of bibliometrics analysis provide a valuable reference for the research direction of radiomics. However, radiomics still faces many challenges in the future, such as the single nature of the data source which may affect the comprehensiveness of the results. Future studies can further expand the data sources and build a multicenter public database to more comprehensively reflect the research status and development trend of CRC radiomics.

[Analysis of three Chinese pedigrees affected with Hereditary factor â ¦ deficiency due to compound heterozygous variants of F7 gene].

OBJECTIVE: To analyze the types of genetic variants and clinical characteristics of three Chinese pedigrees affected with Hereditary coagulation factor Ⅶ (FⅦ) deficiency. METHODS: Three pedigrees who had visited the First Affiliated Hospital of Wenzhou Medical University between December 2021 and October 2022 were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅦ activity (FⅦ:C) were measured in the three probands and their pedigree members. All exons and their flanking sequences were analyzed by direct sequencing, and candidate variants were verified by reverse sequencing. The corresponding variant loci in the family members were also analyzed. ClustalX-2.1-win was used to analyze the conservation of the variant loci. Varcards and Spcards online software was used to predict the pathogenicity of the variants. Pymol software was used to analyze the changes in protein structure and molecular forces. RESULTS: Three cases of hereditary FⅦ deficiency were found to have decreased FⅦ:C, prolonged PT and normal APTT. Genetic analysis identified a total of four genetic variants, and all three probands had harbored compound heterozygous variants of the F7 gene, including p.Cys389Gly and p.His408Gln in proband 1, p.Cys389Gly and IVS6+1G>T in proband 2, and IVS6+1G>T and IVS1a+5G>A in proband 3. Conservation analysis showed that both the p.Cys389 and p.His408 loci are highly conserved among orthologous species. Analysis with Varcards and Spcards software showed that these variants were pathogenic. Protein modeling analysis showed that the p.Cys389Gly and p.His408Gln variants may result in altered protein structures and changes in hydrogen bonds. CONCLUSION: The clinical manifestations of the three FⅦ-deficient probands may be attributed to the compound heterozygous variants of p.Cys389Gly/p.His408Gln, p.Cys389Gly/IVS6+1G>T and IVS6+1G>T/IVS1a+5G>A of the F7 gene. The combination of the three compound heterozygous variants was unreported previously.

HIST3H2A promotes the progression of prostate cancer through inhibiting cell necroptosis.

In recent years, there has been an increase in the incidence and mortality rates of prostate cancer (PCa). However, the specific molecular mechanisms underlying its occurrence and development remain unclear, necessitating the identification of new therapeutic targets. Through bioinformatics analysis, we discovered a previously unstudied differential gene called HIST3H2A in prostate cancer. Our study revealed that HIST3H2A is highly expressed in PCa tissues, as confirmed by analysis of both the GEO and UALCAN databases. Further analysis using the KEGG database demonstrated that HIST3H2A regulates the pathway of programmed necroptosis in cells. Additionally, we observed significant up-regulation of HIST3H2A in PCa tissues and cell lines. HIST3H2A was found to regulate cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) process in tumors. Notably, HIST3H2A's role in regulating programmed necroptosis in prostate cancer cells differs from its role in apoptosis. In vitro and in vivo experiments collectively support the key role of HIST3H2A in promoting the development of prostate cancer, highlighting its potential as a therapeutic target for patients with PCa.

A One-Step RPA-CRISPR Assay Using crRNA Based on Suboptimal Protospacer Adjacent Motif for Vibrio vulnificus Detection.

Vibrio vulnificus is a hazardous foodborne pathogen responsible for approximately 95% of seafood-related deaths. This highlights the urgent requirement for specialized detection tools to be developed and used by food enterprises and food safety authorities. The DETECTR (DNA endonuclease targeted CRISPR trans reporter) system that combines CRISPR/Cas and recombinase polymerase amplification (RPA) has been utilized to develop a molecular detection assay for V. vulnificus. However, because the incompatibility between RPA and Cas12a cleavage has not been addressed, it is a two-step assay that lacks convenience and presents contamination risk. Here, we developed a one-step RPA-CRISPR assay for V. vulnificus using a special crRNA targeting a sequence with a suboptimal protospacer adjacent motif (PAM). The entire assay, conducted at 37°C, takes only 40-60 min, yields results visualized under blue light, and exhibits exceptional specificity and sensitivity (detecting 4 pathogen genome copies per reaction). This study offers a valuable tool for detecting V. vulnificus, aiding in foodborne infection prevention, and exemplifies one-step RPA-CRISPR assays managing Cas-cleavage activity through PAM adjustments.

Efficacy of ScopeGuide-Assisted Training in Enhancing Colonoscopy Competence and Reducing Patient Discomfort.

OBJECTIVE: In this study, we aimed to evaluate the efficacy of the Magnetic Scope Guide Assist (ScopeGuide) in enhancing the procedural competence of endoscopists and reducing patient discomfort during colonoscopy. METHODS: This was a retrospective study with 88 trainee participants. The study participants were trained on patients who underwent colonoscopy without anesthesia. Both ScopeGuide-assisted training and conventional training (without ScopeGuide) were utilized for colonoscopy instruction. The outcomes of training were compared, with a particular emphasis on the competency of looping resolution. RESULTS: ScopeGuide-assisted training was superior to conventional training in multiple aspects, including looping resolution ( Z =-3.681, P <0.001), pain scores ( Z =-4.211, P <0.001), time to reach the cecum ( Z =-4.06, P <0.001), willingness to undergo repeat colonoscopy ( Z =-4.748, P <0.001), competence of positional changes ( Z =-4.079, P <0.001), and the effectiveness of assisted compression ( Z =-3.001, P =0.003). Further stratified analysis revealed that the ScopeGuide-assisted training mode was more beneficial for junior endoscopists ( P <0.05 in all parameters) but not for intermediate endoscopists ( P >0.05) and partially beneficial for senior endoscopists ( P <0.05 for all parameters except looping resolution). CONCLUSION: ScopeGuide-assisted training can significantly facilitate endoscopists in resolving loops and reducing patient pain, thereby enhancing their colonoscopy abilities.

Purification, crystallization and preliminary crystallographic analysis of Chlamydophila pneumoniae AP endonuclease IV.

Base excision is a crucial DNA repair process mediated by endonuclease IV in nucleotide excision. In Chlamydia pneumoniae, CpendoIV is the exclusive AP endonuclease IV, exhibiting DNA replication error-proofreading capabilities, making it a promising target for anti-chlamydial drug development. Predicting the structure of CpendoIV, molecular docking with DNA was performed, analyzing complex binding sites and protein surface electrostatic potential. Comparative structural studies were conducted with E. coli EndoIV and DNA complex containing AP sites.CpendoIV was cloned, expressed in E. coli, and purified via Ni-NTA chelation and size-exclusion chromatography. Low NaCl concentrations induced aggregation during purification, while high concentrations enhanced purity.CpendoIV recognizes and cleaving AP sites on dsDNA, and Zn2+ influences the activity. Crystallization was achieved under 8% (v/v) Tacsimate pH 5.2, 25% (w/v) polyethylene glycol 3350, and 1.91 Å resolution X-ray diffraction data was obtained at 100 K. This research is significant for provides a deeper understanding of CpendoIV involvement in the base excision repair process, offering insights into Chlamydia pneumoniae.

Oral Chinese Herbal Medicine plus usual care for diabetic kidney disease: study protocol for a randomized, double-blind, placebo-controlled pilot trial.

Background: Diabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD. Methods: A mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant's perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants' benefits, the data's credibility, and the results' validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy. Discussion: Conducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD. Trial registration number: https://www.chictr.org.cn/, identifier ChiCTR2200062786.

Antiplatelet effects of the CEACAM1-derived peptide QDTT.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and "inside-out" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.

What is the context? The study focuses on Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its role in platelet activation, particularly through the GPVI/FcRγ-chain pathway.The research aims to identify specific fragments of CEACAM1's extracellular domain that could restrict platelet activation, without increasing bleeding risk.What is new? The researchers identified a peptide called QDTT derived from the A1 domain of CEACAM1's extracellular segment. This peptide demonstrated the ability to inhibit platelet aggregation, secretion, and GP IIb/IIIa activation.The study also revealed that specific amino acids within the QDTT sequence were essential for its inhibitory effects on collagen-induced aggregation.What is the impact? The findings suggest that the A1 domain-derived peptide QDTT from CEACAM1 could serve as a potential basis for developing novel antiplatelet drugs. This peptide effectively limits platelet activation and aggregation without significantly prolonging bleeding time, indicating a promising approach to managing thrombosis and related disorders while minimizing bleeding risks.

Urea nitrogen-to-albumin ratio predicts ventricular aneurysm formation in ST-segment elevation myocardial infarction.

AIMS: Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. The aim of this study was to investigate the possible predictive value of blood urea nitrogen-to-albumin ratio (BAR) for the LVA formation in acute ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 1123 consecutive patients with STEMI were prospectively enrolled. The clinical and laboratory data were compared between LVA group and non-LVA group. Multivariable logistic regression analysis was performed to assess the independent risk factors of LVA formation. Predictive power of BAR and composite variable for LVA formation were assessed using receiver operating characteristic curve. LVA was detected in 162 patients (14.4%). The BAR was significantly higher in patients with LVA [0.16 (0.13-0.19) vs. 0.13 (0.10-0.17), P < 0.001]. Multivariable logistic regression analysis revealed that left ventricular ejection fraction (LVEF) [odds ratio (OR) = 0.865, P < 0.001], culprit vessel-left anterior descending artery (LAD) (OR = 4.705, P < 0.001), and BAR (OR = 2.208, P = 0.018) were all independent predictors for LVA formation. The predictive value of BAR remained significant even after cross-validation by splitting population into training set (OR = 1.957, P = 0.034) and validation set (OR = 1.982, P = 0.039). The maximal length and width of LVA were significantly increased in patients with BAR ≥ 0.15 when compared with BAR < 0.15 (3.37 ± 1.09 vs. 2.92 ± 0.93, P = 0.01, for maximal length, and 2.20 ± 0.55 vs. 1.85 ± 0.63, P = 0.001, for maximal width). The discriminant power of BAR for LVA is 0.723, which is superior to both blood urea nitrogen (C statistic = 0.586, P < 0.001) and albumin (C statistic = 0.64, P < 0.001). The combination of BAR, LVEF, and culprit vessel-LAD could significantly increase the predictive ability (C statistic = 0.874, P < 0.001, for vs. BAR). Subgroup analysis of age, sex, hypertension, diabetes, smoking, LVEF, serum albumin, multiple-vessel disease, and Gensini score had no effect on the association between BAR and risk of LVA formation (P < 0.05 for all subgroups). CONCLUSIONS: A higher BAR was an independent predictor for LVA formation in STEMI patients with primary PCI.

Analysis of PROS1 mutations and clinical characteristics in three Chinese families with hereditary protein S deficiency.

We report three heterozygous PROS1 mutations that caused type I protein S deficiency in three unrelated Chinese families. We measured protein S activity and antigen levels for all participants, screened them for mutations in the PROS1 gene. And we employed the calibrated automated thrombin generation (CAT) method to investigate thrombin generation. Numerous bioinformatics tools were utilized to analyze the conservation, pathogenicity of mutation, and spatial structure of the protein S. Phenotyping analysis indicated that all three probands exhibited simultaneous reduced levels of PS:A, TPS:Ag, and FPS:Ag. Genetic testing revealed that proband A harbored a heterozygous c.458_458delA (p.Lys153Serfs*6) mutation in exon 5, proband B carried a heterozygous c.1687C>T (p.Gln563stop) mutation in exon 14, and proband C exhibited a heterozygous c.200A>C (p.Glu67Ala) mutation in exon 2. Bioinformatic analysis predicted that the p.Lys153Serfs*6 frameshift mutation and the p.Gln563stop nonsense mutation in the protein S were classified as "disease-causing." The identification of the novel mutation p.Lys153Serfs*6 in PROS1 enriches the Human Genome Database. Our research suggests that these three mutations (p.Lys153Serfs*6, p.Gln563stop, and p.Glu67Ala) are possibly responsible for the decreased level of protein S in the three families. Furthermore, the evidence also supports the notion that individuals who are asymptomatic but have a family history of PSD can benefit from genetic analysis of the PROS1 gene.

Ultrasensitive one-pot detection of monkeypox virus with RPA and CRISPR in a sucrose-aided multiphase aqueous system.

IMPORTANCE: The monkeypox virus was declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) and continues to cause infection cases worldwide. Given the risk of virus evolution, it is essential to identify monkeypox virus infection in a timely manner to prevent outbreaks. This study establishes a novel one-pot recombinase polymerase amplification-Clustered Regularly Interspaced Short Palindromic Repeats (RPA-CRISPR) assay for monkeypox virus with an ultra-high sensitivity. The assay shows good specificity, accuracy, and the rapidness and convenience important for point-of-care testing. It provides an effective tool for the early diagnosis of monkeypox, which is useful for the prevention of an epidemic.

Analysis of PROC mutations and clinical features in 22 unrelated families with inherited protein C deficiency.

Currently, limited information is available in the literature regarding the relationships between PROC mutations and clinical features in Chinese individuals. We aimed to characterize severe congenital Protein C deficiency in 22 unrelated Chinese families in a tertiary hospital by analyzing its clinical manifestation, associated risk factors, and gene mutations. We measured protein C activity and antigen levels for all participants, screened them for mutations in the PROC gene, and analyzed the clinical features of each family to identify commonalities and differences. The analysis revealed a total of 75 individuals with PCD and 16 different PROC mutations, including 12 missense mutations and 4 deletion mutations. Among them, 11 who were compound heterozygotes or homozygotes for mutations tended to develop symptoms at a younger age without any clear triggers. In contrast, the remaining 64 individuals who were heterozygotes for mutations often had clear triggers for their symptoms and experienced a milder course of the disease. It is worth noting that the mutation c.565C > T occurred most frequently, being identified in 8 out of 22 families (36%). Our team also reported five novel mutations, including c.742-744delAAG, c.383G > A, c.997G > A, c.1318C > T, and c.833T > C mutations. The identification of five novel mutations adds to the richness of the Human Genome Database. Asymptomatic heterozygotes are not uncommon, and they are prone to develop symptoms with obvious triggers. The evidence presented strongly suggest that asymptomatic individuals with family history of protein C deficiency can benefit from mutational analysis of PROC gene.

Implementation of Tunneled Peripherally Inserted Central Catheters Placement in Cancer Patients: A Randomized Multicenter Study.

This study sought to evaluate the impact of the subcutaneous tunneling technique on peripherally inserted central catheter (PICC) placement. We randomized 694 patients who needed PICC placement to either the tunneled PICCs (experimental group) or the non-tunneled PICCs (control group) from August to December 2021. The cumulative frequency of complications was assessed as the primary outcome. Secondary outcomes comprised of the amount of bleeding, catheter insertion time, self-reported pain score, and one-puncture success rate. After 6 months of follow-up, the tunneled PICCs group showed a significant decrease in the frequency of total complications, especially in infection (3.0% vs. 7.1%, p = .021) and catheter-related thrombosis (3.3% vs. 8.3%, p = .008), although approximately 0.5 ml bleeding and 3.5 min time were increased. This randomized multicenter study supports the efficacy of subcutaneous tunneling technology in reducing PICC-related complications, enhancing patient comfort, and encouraging using subcutaneous tunneling technology for PICC placement.

Interference of MDM2 attenuates vascular endothelial dysfunction in hypertension partly through blocking Notch1/NLRP3 inflammasome pathway.

BACKGROUND: Hypertension is a life-threatening disease mainly featured as vascular endothelial dysfunction. This study aims to explore the regulatory role of murine double minute 2 (MDM2) in hypertension and vascular damage. METHODS: Mice were infused with angiotensin II (AngII) to establish a hypertension mouse model in vivo and AngII-stimulated HUVECs were constructed to simulate the damage of vascular endothelial cells in hypertension in vitro. The plasmids targeting to MDM2 was injected to mice or transfected to HUVECs. qRT-PCR and western blot were performed to detect corresponding gene expression in mice aorta. Blood pressure was measured. H&E and Masson staining were conducted to evaluate histological changes of aorta. Responses to the acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in aorta. ZO-1 expression and cell apoptosis were detected by immunofluorescence and TUNEL, respectively. Network formation ability was determined employing a tube formation. RESULTS: MDM2 was upregulated in hypertensive mice. Knockdown of MDM2 inhibited AngII-induced high BP, histological damage, vascular relaxation to Ach, and promoted the levels of p-eNOS and ZO-1 in the aorta in hypertensive mice. MDM2 knockdown inactivated Notch1 signaling and NLRP3 inflammasome, while the inhibitory effect of MDM2 knockdown on NLRP3 inflammasome activation was partly restored by the activation of Notch1. Furthermore, knockdown of MDM2 relieved AngII-induced endothelial dysfunction in HUVECs, as well as suppressing AngII-promoted cell apoptosis. Whereas, the impacts generated by MDM2 knockdown were partly weakened by the activation of Notch1 signaling or NLRP3 inflammasome. CONCLUSION: In summary, knockdown of MDM2 can attenuate vascular endothelial dysfunction in hypertension, which may be achieved through inhibiting the activation of Notch1 and NLRP3 inflammasome.

Molecular and clinical characterization of two unrelated families with factor V deficiency, including a novel nonsense variant (p.Gln1532*).

BACKGROUND: Factor V (FV) is an essential cofactor in the coagulation cascade. The characterization of novel mutations is advantageous for the clinical management of FV-deficient patients. METHODS: Coagulation screening and thrombin generation assay were performed with the plate-poor plasma. All 25 exons of the F5 gene were amplified and sequenced. The ClustalX-2.1 software was applied to the multiple sequence alignment. The possible adverse effects of mutations were investigated with online bioinformatics software and protein modeling. RESULTS: Two unrelated families with FV deficiency were under investigation. Proband A was an 18-year-old youth with recurrent epistaxis. Proband B was a 29-year-old woman who did not present with any bleeding symptoms. Three heterozygous mutations (p.Gln1532*, p.Phe218Ser, and p.Asp2222Gly) were detected. Interestingly, they were compound heterozygotes and both contained the p.Asp2222Gly, a polymorphism. The thrombin generation assay showed that both patients had impaired ability of thrombin generation, and in particular, proband A was more severe. Conservation, pathogenicity and protein modeling studies all indicated that these three mutations could cause deleterious effects on the function and structure of FV. CONCLUSION: These three mutations are responsible for the FV-deficient in two pedigrees. Moreover, the nonsense variant p.Gln1532* is first reported in the world.