Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes.

Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.

A p21 Reporter iPSC Line for Evaluating CRISPR-Cas9 and Vector-Induced Stress Responses.

CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors (IDLVs) induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors.

Exposure to greenspaces sourced soils improves mice gut microbiota.

Greenspaces are important components of our living environment and have been linked to various human health. However, the mechanisms underlying the linkages remain unclear. Enriching microbiota has emerged as a novel mechanism, but the corresponding evidence is still limited. We collected soil samples from forest land, grassland, and barren land in Zunyi City, southwestern China and prepared soil solutions. A total of 40 BALB/c mice were evenly divided into normal control group, model control group, forest soil group, grassland soil group, and barren land soil group. After establishing the pseudo germ-free mouse model, different soil solutions were administered through gavage, lasting for seven weeks. Fecal samples were collected and a 16S rRNA high-throughput sequencing analysis was performed. Then, alpha- and beta-diversity were calculated and employed to estimate the effects of soil exposures on mice gut microbial diversity and composition. Further, Linear Discriminant Analysis Effect Size (LEfSe) analysis was carried out to evaluate the effects of soil exposures on gut microbiota specific genera abundances and functional pathways. Compared to mice exposed to barren land soils, those exposed to soils sourced from forest land showed an increase of 0.43 and 70.63 units in the Shannon index and the Observed ASVs, respectively. In addition, exposure to soils sourced from forest land and grassland resulted in healthier changes (i.e., more short-chain fatty acids (SCFAs)-producing bacteria) in gut microbiota than those from barren land. Furthermore, mice exposed to forest soil and grassland soil showed enrichment in 5 and 3 pathways (e.g., butanoate metabolism) compared to those exposed to barren land soil, respectively. In conclusion, exposure to various greenspaces soils may modify the gut microbial communities of mice, potentially fostering a more beneficial microbiota profile. Further better-designed studies are needed to validate the current findings and to explore the effects of greenspace related gut microbiota on human health.

Diversity and Activity of Soil N2O-Reducing Bacteria Shaped by Urbanization.

Nitrous oxide (N2O) is a potent greenhouse gas with various production pathways. N2O reductase (N2OR) is the primary N2O sink, but the distribution of its gene clades, typically nosZI and atypically nosZII, along urbanization gradients remains poorly understood. Here we sampled soils from forests, parks, and farmland across eight provinces in eastern China, using high-throughput sequencing to distinguish between two N2O-reducing bacteria clades. A deterministic process mainly determined assemblies of the nosZI communities. Homogeneous selection drove nosZI deterministic processes, and both homogeneous and heterogeneous selection influenced nosZII. This suggests nosZII is more sensitive to environmental changes than nosZI, with significant changes in community structure over time or space. Ecosystems with stronger anthropogenic disturbance, such as urban areas, provide diverse ecological niches for N2O-reducing bacteria (especially nosZII) to adapt to environmental fluctuations. Structural equation modeling (SEM) and correlation analyses revealed that pH significantly influences the community composition of both N2O-reducing bacteria clades. This study underscores urbanization's impact on N2O-reducing bacteria in urban soils, highlighting the importance of nosZII and survival strategies. It offers novel insights into the role of atypical denitrifiers among N2O-reducing bacteria, underscoring their potential ecological importance in mitigating N2O emissions from urban soils.

A convenient research strategy for functional verification of epigenetic regulators during spermatogenesis.

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.

A New Orthonairovirus Associated with Human Febrile Illness.

BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

Mechanisms Underlying the Therapeutic Effects of Nicotinamide Mononucleotide in Treating High-Fat Diet-induced Hypertrophic Cardiomyopathy based on GEO Datasets, Network Pharmacology, and Molecular Docking.

BACKGROUND: The beneficial effects of nicotinamide mononucleotide (NMN) on heart disease have been reported, but the effects of NMN on high-fat diet-induced hypertrophic cardiomyopathy (HCM) and its mechanisms of action are unclear. In this study, we systematically explored the effects and mechanism of action of NMN in HCM using network pharmacology and molecular docking. METHODS: Active targets of NMN were obtained from SWISS, CNKI, PubMed, DrugBank, BingingDB, and ZINC databases. HCM-related targets were retrieved from GEO datasets combined with GeneCards, OMIM, PharmGKB, and DisGeNET databases. A Protein-Protein Interaction (PPI) network was built to screen the core targets. DAVID was used for GO and KEGG pathway enrichment analyses. The tissue and organ distribution of targets was evaluated. Interactions between potential targets and active compounds were assessed by molecular docking. A molecular dynamics simulation was conducted for the optimal core protein-compound complexes obtained by molecular docking. RESULTS: In total, 265 active targets of NMN and 3918 potential targets of HCM were identified. A topological analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of NMN were mediated by genes related to inflammation, apoptosis, and oxidative stress, as well as the FOXO and PI3K-Akt signaling pathways. Molecular docking and molecular dynamics simulations revealed good binding ability between the active compounds and screened targets. CONCLUSION: The possible targets and pathways of NMN in the treatment of HCM have been successfully predicted by this investigation. It provides a novel approach for further investigation into the molecular processes of NMN in HCM treatment.

Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-Aged and Elderly: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Nicotinamide Mononucleotide (NMN) has gained attention as a precursor to Nicotinamide Adenine Dinucleotide (NAD+) in recent years, commonly utilized in anti-aging therapies. The anti-aging effects of NMN on muscle and liver functions in middleaged and elderly people are still unclear. OBJECTIVE: Based on available randomized controlled trials, we conducted a meta-analysis to evaluate the impact of NMN on muscle and liver functions in middle-aged and elderly individuals. METHODS: We conducted searches on three electronic databases (PubMed, Embase, Web of Science) for randomized controlled trials involving NMN interventions in middle-aged and elderly populations. Through the Cochrane Handbook, we assessed the specific methodological quality. All statistical analyses were obtained by Stata15, and statistical significance was set as P<0.05. RESULTS: There were 412 participants from 9 studies in this meta-analysis. Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass. Moreover, NMN had a better effect on ALT (SMD: -0.29 IU/L, 95%CI [-0.55, -0.03] p = 0.028). Subgroup analysis indicated that administering a small dose of NMN exerted the most prominent impact on Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). CONCLUSION: NMN has positive efficacy in enhancing muscle function, reducing insulin resistance and lowering aminotransferase levels in middle-aged and elderly individuals. NMN is an encouraging and considerable drug for anti-aging treatment.

Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (Mpro).

Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 and its variants, has further highlighted the urgent need for the development of effective therapeutic agents. Currently, the highly conserved and broad-spectrum nature of main proteases (Mpro) renders them of great importance in the field of inhibitor study. In this study, we categorize inhibitors targeting Mpro into three major groups: mimetic, nonmimetic, and natural inhibitors. We then present the research progress of these inhibitors in detail, including their mechanism of action, antiviral activity, pharmacokinetic properties, animal experiments, and clinical studies. This review aims to provide valuable insights and potential avenues for the development of more effective antiviral drugs against SARS-CoV-2.

Depressive symptom mediates the association between the number of chronic diseases and cognitive impairment: a multi-center cross-sectional study based on community older adults.

Objective: The purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults. Method: Participants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents' depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment. Result: A total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P<0.05). Depressive symptom had a mediating effect in the number of chronic diseases and cognitive impairment, and the mediating effect (1.109) accounted for 44.13% of the total effect (0.247). Conclusion: The mental health of the older adult needs to be taken seriously, and improving depressive symptom can reduce the occurrence of cognitive impairment in older patients with MCC to a certain extent.

Intestinal microbiota by angiotensin receptor blocker therapy exerts protective effects against hypertensive damages.

Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB-treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.

Vagus nerve stimulation (VNS) preventing postoperative cognitive dysfunction (POCD): two potential mechanisms in cognitive function.

Postoperative cognitive dysfunction (POCD) impacts a significant number of patients annually, frequently impairing their cognitive abilities and resulting in unfavorable clinical outcomes. Aimed at addressing cognitive impairment, vagus nerve stimulation (VNS) is a therapeutic approach, which was used in many mental disordered diseases, through the modulation of vagus nerve activity. In POCD model, the enhancement of cognition function provided by VNS was shown, demonstrating VNS effect on cognition in POCD. In the present study, we primarily concentrates on elucidating the role of the VNS improving the cognitive function in POCD, via two potential mechanisms: the inflammatory microenvironment and epigenetics. This study provided a theoretical support for the feasibility that VNS can be a potential method to enhance cognition function in POCD.

A Novel Animal Model for Pulmonary Hypertension: Lung Endothelial-Specific Deletion of Egln1 in Mice.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by high blood pressure in the pulmonary arteries, which can potentially lead to heart failure over time. Previously, our lab found that endothelia-specific knockout of Egln1, encoding prolyl 4-hydroxylase-2 (PHD2), induced spontaneous pulmonary hypertension (PH). Recently, we elucidated that Tmem100 is a lung-specific endothelial gene using Tmem100-CreERT2 mice. We hypothesize that lung endothelial-specific deletion of Egln1 could lead to the development of PH without affecting Egln1 gene expression in other organs. Tmem100-CreERT2 mice were crossed with Egln1 flox/flox mice to generate Egln1 f/f ;Tmem100-CreERT2 (LiCKO) mice. Western blot and immunofluorescent staining were performed to verify the knockout efficacy of Egln1 in multiple organs of LiCKO mice. PH phenotypes, including hemodynamics, right heart size and function, pulmonary vascular remodeling, were evaluated by right heart catheterization and echocardiography measurements. Tamoxifen treatment induced Egln1 deletion in the lung endothelial cells (ECs) but not in other organs of adult LiCKO mice. LiCKO mice exhibited an increase in right ventricular systolic pressure (RVSP, ~35 mmHg) and right heart hypertrophy. Echocardiography measurements showed right heart hypertrophy, as well as cardiac and pulmonary arterial dysfunction. Pulmonary vascular remodeling, including increased pulmonary wall thickness and muscularization of distal pulmonary arterials, was enhanced in LiCKO mice compared to wild-type mice. Tmem100 promoter-mediated lung endothelial knockout of Egln1 in mice leads to development of spontaneous PH. LiCKO mice could serve as a novel mouse model for PH to study lung and other organ crosstalk.

A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): a prospective, multicenter, randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings. METHODS: The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in postinguinal hernia surgery (IHS) patients. The patients were randomly assigned (1:1) to the intervention or control arm. The intervention group used the three-factor model to identify patients at moderate or high risk of VTE for subsequent prophylaxis according to clinical guidelines. Both groups were followed for 4 weeks, with randomization implemented using computer-generated sequences. The primary outcome measured was the rate of VTE prophylaxis. Secondary outcomes included time spent on VTE risk assessment (surgeon self-reported), postoperative D-dimer trends, perioperative VTE occurrence, bleeding events, and the net clinical benefit. RESULTS: Of the 1109 participants, 508 in the experimental group and 601 in the control group completed follow-up. The three-factor model showed higher VTE prophylaxis rates in all patients (pharmacologic prophylaxis: 26.2 vs. 6.00%, P <0.001) and particularly in those at high risk (pharmacologic prophylaxis: 57.3 vs. 9.50%, P <0.001). The experimental group significantly reduced VTE risk assessment time compared to the Caprini score (1.39±0.55 min vs. 5.73±1.35 min, P <0.001). The experimental group had lower D-dimer levels (0.26±0.73 mg/l vs. 0.35±0.55 mg/l, P =0.028). In the experimental group, the patients did not experience an increased risk of VTE (0 vs. 1.66%, P =0.268) and bleeding (1.18 vs. 0.67%, P =0.558) compared to the controls. There was no significant difference in net clinical benefit, which combined VTE and bleeding events, between the experimental and control groups (1.18 vs. 0.83%, P =0.559). CONCLUSION: Applying the simple three-factor model in perioperative VTE management could quickly identify the patient with a high risk of VTE and improve the prophylaxis rate of perioperative VTE.

Harnessing three-dimensional porous chitosan microsphere embedded with adipose-derived stem cells to promote nerve regeneration.

BACKGROUND: Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. METHODS: In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. RESULTS: Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. CONCLUSIONS: The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.

A prospective study of two-dimensional ultrasonography combined with shear wave elastography for pregnancy-related diastasis recti abdominis.

Objectives: To compare the inter-rectus distance (IRD), rectus abdominis thickness (RAT), and stiffness in women during pregnancy and postpartum and identify the risk and protective factors affecting diastasis recti abdominis (DRA). Materials and methods: A total of 171 pregnant women who volunteered to participate in this study were recruited. Using an ultrasonographic diagnostic instrument with shear wave elastography function, IRD, RAT and the Young's modulus of the rectus abdominis muscles were measured at 12 weeks, 37 weeks of pregnancy, and 6 weeks postpartum. Results: The IRD at 37 weeks was significantly higher than that at 12 weeks and then decreased at 6 weeks postpartum, but it was still higher than that at 12 weeks (p < 0.001). RAT and Young's modulus decreased significantly at 37 weeks compared with those at 12 weeks and then recovered at 6 weeks postpartum, but they were lower than those at 12 weeks (p < 0.001). IRD at 12 weeks was significantly higher in multiparae than in primiparae (p < 0.001). Moreover, positive correlation between the RAT and Young's modulus of rectus abdominis muscles at 12 and 37 weeks of gestation and 6 weeks postpartum (p < 0.001) was observed. Multiple linear regression analysis showed that the regression equation was significant (f = 24.856, p < 001). Conclusion: Our study identified differences in IRD, thickness and stiffness of the rectus abdominis muscle between early and advanced pregnancy and the postpartum period. The risk and protective factors of DRA may guide pregnant women's protection and treatment.

Traditional Chinese medicine for post-viral olfactory dysfunction: A systematic review.

Background: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD. Methods: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis. Results: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection). Conclusions: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit. Protocol registration: The protocol of this review was registered at PROSPERO: CRD42022366776.

[Prognostic Factors Affecting Recurrence in Peripheral T-Cell Lymphoma Patients with Different HDAC Levels].

OBJECTIVE: To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma (PTCL) patients with different levels of histone deacetylase (HDAC) based on latent class analysis. METHODS: 112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group. The clinical data of the two groups of patients were compared. Multivariate logistic regression was used to analyze the risk factors for recurrence. Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group. RESULTS: There were 87 patients (77.68%) in recurrence group and 25 patients (22.32%) in non-recurrence group. The result of multivariate logistic regression showed that ECOG score ≥2, Ann Arbor stage III-IV, IPI score >2, bone marrow involvement, elevated serum ß2-microglobulin (ß2-MG), short-term efficacy not reaching complete remission (CR) or partial remission (PR), and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL (P <0.05). The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels (P <0.05). The results of cluster analysis showed that the risk of recurrence was obviously clustered, and the patients could be divided into high recurrence risk group (HDAC＞5 points) and low recurrence risk group (HDAC≤5 points). The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group, compared with the low recurrence risk group (P <0.05). CONCLUSION: There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.