LGBTQ Utilization of a Statewide Tobacco Quitline: Engagement and Quitting Behavior, 2010-2022.

INTRODUCTION: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals use tobacco at disproportionately high rates but are as likely as straight tobacco users to want to quit and to use quitlines. Little is known about the demographics and geographic distribution of LGBTQ quitline participants, their engagement with services, or their long-term outcomes. AIMS AND METHODS: Californians (N = 333 429) who enrolled in a statewide quitline 2010-2022 were asked about their sexual and gender minority (SGM) status and other baseline characteristics. All were offered telephone counseling. A subset (n = 19 431) was followed up at seven months. Data were analyzed in 2023 by SGM status (LGBTQ vs. straight) and county type (rural vs. urban). RESULTS: Overall, 7.0% of participants were LGBTQ, including 7.4% and 5.4% of urban and rural participants, respectively. LGBTQ participants were younger than straight participants but had similar cigarette consumption. Fewer LGBTQ participants reported a physical health condition (42.1% vs. 48.4%) but more reported a behavioral health condition (71.1% vs. 54.5%; both p's < .001). Among both LGBTQ and straight participants, nearly 9 in 10 chose counseling and both groups completed nearly three sessions on average. The groups had equivalent 30-day abstinence rates (24.5% vs. 23.2%; p = .263). Similar patterns were seen in urban and rural subgroups. CONCLUSIONS: LGBTQ tobacco users engaged with and appeared to benefit from a statewide quitline even though it was not LGBTQ community-based. A quitline with staff trained in LGBTQ cultural competence can help address the high prevalence of tobacco use in the LGBTQ community and reach members wherever they live. IMPLICATIONS: This study describes how participants of a statewide tobacco quitline broke down by sexual orientation and gender. It compares participants both by SGM status and by type of county to provide a more complete picture of quitline participation both in urban areas where LGBTQ community-based cessation programs may exist and in rural areas where they generally do not. To our knowledge, it is the first study to compare LGBTQ and straight participants on their use of quitline services and quitting aids, satisfaction with services received, and rates of attempting quitting and achieving prolonged abstinence from smoking.

An anatomical study of the tibial nerve branches innervating the posterior tibial artery.

The arteries of the lower limbs are innervated by vascular branches (VBs) originating from the lumbar sympathetic trunk and branches of the spinal nerve. Although lumbar sympathectomy is used to treat nonreconstructive critical lower limb ischemia (CLLI), it has limited long-term effects. In addition, the anatomical structure of tibial nerve (TN) VBs remain incompletely understood. This study aimed to clarify their anatomy and better inform the surgical approach for nonreconstructive CLLI. Thirty-six adult cadavers were dissected under surgical microscopy to observe the patterns and origin points of VBs under direct vision. The calves were anatomically divided into five equal segments, and the number of VB origin points found in each was expressed as a proportion of the total found in the whole calf. Immunofluorescence staining was used to identify the sympathetic nerve fibers of the VBs. Our results showed that the TN gave off 3-4 VBs to innervate the posterior tibial artery (PTA), and the distances between VBs origin points and the medial tibial condyle were: 24.7 ± 16.3 mm, 91.7 ± 66.1 mm, 199.6 ± 52.0 mm, 231.7 ± 38.5 mm, respectively. They were mainly located in the first (40.46%) and fourth (31.68%) calf segments, and immunofluorescence staining showed that they contained tyrosine hydroxylase-positive sympathetic nerve fibers. These findings indicate that the TN gives off VBs to innervate the PTA and that these contain sympathetic nerve fibers. Therefore, these VBs may need to be cut to surgically treat nonreconstructable CLLI.

Coumarin protects Cherax quadricarinatus (red claw crayfish) against white spot syndrome virus infection.

Coumarin is a natural compound from plants with the molecular formula C9H6O2. Cherax quadricarinatus (red claw crayfish) is an aquaculture species exhibiting high economic efficiency and quality that is mainly distributed and cultivated in the southeast provinces in China. In order to identify an effective herbal immunopotentiator against white spot syndrome virus (WSSV) infection, this study examined the effect of coumarin as a feed additive in protecting C. quadricarinatus against WSSV infection. The expression of immune-related genes and WSSV copies were analyzed by Q-PCR. Challenge experiments were conducted to analyze the survival rate and determine the optimal concentration of coumarin. The Phenoloxidase activity (PO), Acid phosphatase (ACP) and superoxide dismutase activity (SOD) activity and lysozyme activity were also analyzed. Total hemocyte count (THC) and apoptosis rate were determined by flow cytometry. The WSSV challenge results showed that 40 mg/kg coumarin reduced the mortality of C. quadricarinatus and delayed the WSSV infection process. Further investigation showed that coumarin treatment had a positive effect on the important immunity-related parameters THC, ACP activity, SOD activity, LZM and PO activity. Coumarin up-regulated the expression of proPO, JAK, STAT, ALF, Hsp70 and down-regulated the expression of caspase at the mRNA level. After WSSV infection, the hemocyte apoptosis rate was lower in the 40 mg/kg coumarin + WSSV group compared with the WSSV only group. These data illustrate that coumarin enhances innate immunity in C. quadricarinatus and exhibits a protective effect against WSSV infection by reducing the number of WSSV copies and slowing the process of infection, which provides a potential theoretical basis for studies of coumarin as a new aquatic feed additive in crustacean aquaculture.

Early adoption of heated tobacco products resembles that of e-cigarettes.

BACKGROUND: Heated tobacco products (HTP) generate nicotine-containing aerosol by heating tobacco rather than burning it. The US Food and Drug Administration (FDA) has recently authorised the sale of one HTP brand, iQOS, in the USA. This study examined the awareness, use and risk perceptions of HTP in the USA following FDA authorisation. METHODS: A national probability sample of 20 449 US adults completed an online survey between November 2019 and February 2020. In addition to assessing awareness and use of HTP, two ratios were calculated: the ratio of those who experimented with HTP given that they had heard about it (E/H) and the ratio of those who currently used HTP given experimentation (C/E). These ratios for HTP were compared against those for e-cigarettes from a similar national survey in 2012. RESULTS: Overall, 8.1% of respondents had heard of HTP. Only 0.55% had tried and 0.10% were current users. The rate of experimentation among those who heard about HTP and the rate of current use among experimenters were, however, similar to those for e-cigarettes in 2012: E/H and C/E for HTP were 6.8% and 18.2%, respectively; and 10.7% and 17.8%, respectively for e-cigarettes. The majority of respondents considered HTP either less harmful than (11.6%), or equally harmful as e-cigarettes (42.7%). CONCLUSIONS: Only a small fraction of US population in 2020 have tried any HTP. However, the similarity in early adoption rates following awareness, suggests that future adoption for HTP may be similar to that for e-cigarettes, if HTP are marketed more aggressively.

The Molecular Genetics of Marfan Syndrome.

Marfan syndrome (MFS) is a complex connective tissue disease that is primarily characterized by cardiovascular, ocular and skeletal systems disorders. Despite its rarity, MFS severely impacts the quality of life of the patients. It has been shown that molecular genetic factors serve critical roles in the pathogenesis of MFS. FBN1 is associated with MFS and the other genes such as FBN2, transforming growth factor beta (TGF-ß) receptors (TGFBR1 and TGFBR2), latent TGF-ß-binding protein 2 (LTBP2) and SKI, amongst others also have their associated syndromes, however high overlap may exist between these syndromes and MFS. Abnormalities in the TGF-ß signaling pathway also contribute to the development of aneurysms in patients with MFS, although the detailed molecular mechanism remains unclear. Mutant FBN1 protein may cause unstableness in elastic structures, thereby perturbing the TGF-ß signaling pathway, which regulates several processes in cells. Additionally, DNA methylation of FBN1 and histone acetylation in an MFS mouse model demonstrated that epigenetic factors play a regulatory role in MFS. The purpose of the present review is to provide an up-to-date understanding of MFS-related genes and relevant assessment technologies, with the aim of laying a foundation for the early diagnosis, consultation and treatment of MFS.

High-performance gas sensors based on a thiocyanate ion-doped organometal halide perovskite.

Thin films of a thiocyanate ion (SCN-)-doped organometal halide perovskite, CH3NH3PbI3-x(SCN)x, were used as a sensing material for developing high-performance gas sensors. The CH3NH3PbI3-x(SCN)x-based chemiresistor-type sensor can sensitively and selectively detect acetone and nitrogen dioxide (NO2) at room temperature with high sensitivities of 5.6 × 10-3 and 5.3 × 10-1 ppm-1. The limits of detection for acetone and NO2 were measured to be 20 ppm and 200 ppb. This sensor also exhibited excellent repeatability, and its environmental stability was greatly improved by doping the perovskite with SCN- ions.

Long-term e-cigarette use and smoking cessation: a longitudinal study with US population.

BACKGROUND: E-cigarettes have grown popular. The most common pattern is dual use with conventional cigarettes. Dual use has raised concerns that it might delay quitting of cigarette smoking. This study examined the relationship between long-term use of e-cigarettes and smoking cessation in a 2-year period. METHODS: A nationally representative sample of 2028 US smokers were surveyed in 2012 and 2014. Long-term e-cigarette use was defined as using e-cigarettes at baseline and follow-up. Use of e-cigarettes only at baseline or at follow-up was defined as short-term use. Non-users did not use e-cigarettes at either survey. Quit attempt rates and cessation rates (abstinent for 3 months or longer) were compared across the three groups. RESULTS: At 2-year follow-up, 43.7% of baseline dual users were still using e-cigarettes. Long-term e-cigarette users had a higher quit attempt rate than short-term or non-users (72.6% vs 53.8% and 45.5%, respectively), and a higher cessation rate (42.4% vs 14.2% and 15.6%, respectively). The difference in cessation rate between long-term users and non-users remained significant after adjusting for baseline variables, OR=4.1 (95% CI 1.5 to 11.4) as did the difference between long-term users and short-term users, OR=4.8 (95% CI 1.6 to 13.9). The difference in cessation rate between short-term users and non-users was not significant, OR=0.9 (95% CI 0.5 to 1.4). Among those making a quit attempt, use of e-cigarettes as a cessation aid surpassed that of FDA-approved pharmacotherapy. CONCLUSIONS: Short-term e-cigarette use was not associated with a lower rate of smoking cessation. Long-term use of e-cigarettes was associated with a higher rate of quitting smoking.

Comparison of smoking cessation between education groups: findings from 2 US National Surveys over 2 decades.

OBJECTIVES: We examined smoking cessation rate by education and determined how much of the difference can be attributed to the rate of quit attempts and how much to the success of these attempts. METHODS: We analyzed data from the National Health Interview Survey (NHIS, 1991-2010) and the Tobacco Use Supplement to the Current Population Survey (TUS-CPS, 1992-2011). Smokers (≥ 25 years) were divided into lower- and higher-education groups (≤ 12 years and >12 years). RESULTS: A significant difference in cessation rate between the lower- and the higher-education groups persisted over the last 2 decades. On average, the annual cessation rate for the former was about two thirds that of the latter (3.5% vs 5.2%; P<.001, for both NHIS and TUS-CPS). About half the difference in cessation rate can be attributed to the difference in quit attempt rate and half to the difference in success rate. CONCLUSIONS: Smokers in the lower-education group have consistently lagged behind their higher-education counterparts in quitting. In addition to the usual concern about improving their success in quitting, tobacco control programs need to find ways to increase quit attempts in this group.

Synthesis of a Class of Chiral-Bridged Phosphoramidite Ligands and Their Applications in the First Iridium-Catalyzed Asymmetric Addition of Arylboronic Acids to Isatins.

A series of novel chiral phosphoramidite ligands based on chiral-bridged biphenyl backbones have been prepared conveniently and characterized. The ligands complexed with [IrCodCl]2 provided the first iridium catalyst system for the asymmetric addition of arylboronic acids to N-protected isatins with high efficiency. When performed in THF/H2O at 80 °C with 2 equiv of the arylboronic acids, the transformations acquired good to excellent results (up to 98% yield and 95% ee).

Population support before and after the implementation of smoke-free laws in the United States: trends from 1992-2007.

INTRODUCTION: Several states implemented comprehensive smoke-free laws in workplaces (14 states), restaurants (17 states), and bars (13 states) between 2002 and 2007. We tested the hypothesis that public support for smoke-free laws increases at a higher rate in states that implemented smoke-free laws between 2002 and 2007 (group A) than in states that implemented smoke-free laws after that time or not at all (group B). The period before the implementation (1992-2001) was also considered. METHODS: Data was used from the Current Population Survey (CPS) Tobacco Use Supplements (TUS), which is representative for the U.S. adult population. Respondents were asked whether they thought smoking should not be allowed in indoor work areas, restaurants, and bars and cocktail lounges. Differences in trends were analyzed with binomial mixed effects models. RESULTS: Population support for smoke-free restaurants and bars was higher among group A than among group B before 2002. After 2002, support for smoke-free restaurants and bars increased at a higher rate among group A than among group B. Population support for smoke-free workplaces did not differ between group A and B, and the increase in support for smoke-free workplaces also did not differ between these groups. CONCLUSIONS: The positive association between the implementation of smoke-free restaurant and bar laws and the rate of increase in support for these laws partly supported the hypothesis. The implementation of the laws may have caused support to increase, but also states that have higher support may have been more likely to implement smoke-free laws.

Do smokers support smoke-free laws to help themselves quit smoking? Findings from a longitudinal study.

BACKGROUND: A growing number of smokers support smoke-free laws. The theory of self-control provides one possible explanation for why smokers support laws that would restrict their own behaviour: the laws could serve as a self-control device for smokers who are trying to quit. OBJECTIVE: To test the hypothesis that support for smoke-free laws predicts smoking cessation. METHODS: We used longitudinal data (1999-2000) from a US national sample of adult smokers (n=6415) from the Current Population Survey, Tobacco Use Supplements. At baseline, smokers were asked whether they made a quit attempt in the past year. They were also asked whether they thought smoking should not be allowed in hospitals, indoor sporting events, indoor shopping malls, indoor work areas, restaurants, or bars and cocktail lounges. At 1-year follow-up, smokers were asked whether they had quit smoking. FINDINGS: Smokers who supported smoke-free laws were more likely to have made a recent quit attempt. At 1-year follow-up, those who supported smoke-free laws in 4-6 venues were more likely to have quit smoking (14.8%) than smokers who supported smoke-free laws in 1-3 venues (10.6%) or smokers who supported smoke-free laws in none of the venues (8.0%). These differences were statistically significant in multivariate analyses controlling for demographics. CONCLUSIONS: Support for smoke-free laws among smokers correlates with past quit attempts and predicts future quitting. These findings are consistent with the hypothesis that some smokers support smoke-free laws because the laws could help them quit smoking.

Revisit of the anatomy of the distal perforator of the descending genicular artery and clinical application of its perforator "propeller" flap in the reconstruction of soft tissue defects around the knee.

PURPOSE: In this article,we revisited the anatomy of the distal perforator of the descending genicular artery (DGA) and report the clinical application of its perforator propeller flap in the reconstruction of soft tissue defects around the knee. METHODS: Forty fresh human lower limbs were dissected to redefine the anatomy of the branches of the DGA and their perforators and the anatomical landmarks for clinical applications. Five patients underwent "propeller" distal anteromedial thigh (AMT) flaps based on DGA perforators for the reconstruction of post-traumatic (n = 4) and post-oncologic (n = 1) soft tissue defects occurring near the knee with a size ranging from 4.8 cm × 6.2 cm to 10.5 cm × 18.2 cm. RESULTS: A constant cutaneous perforator of the osteoarticular branch (OAB) of the DGA was found in the distal AMT fossa with a mean caliber of 1.2 ± 0.4 mm. It arose 9.4 ± 3.1 cm distally to the origin of the OAB and 4.0 ± 0.4 cm above the knee joint. The size of the harvested flaps ranged from 6.0 cm × 7.1 cm to 11.0 cm × 20.1 cm. All the flaps healed uneventfully at a mean period of 7.4 months. All the patients regained full range motion of the knee-joint. CONCLUSION: Our study provided evidence of the vascular supply and the clinical application of the distal AMT flap based on a constant perforator arising from the OAB of the DGA. This flap may be a versatile alternative for the reconstruction of the defects around the knee because of its consistent vascular pedicle, pliability and thinness, adequate retrograde perfusion, and the possible direct suture of the donor site.

Impact of epidemic prevention policies on public vaccination willingness: empirical research in China.

Background: The sudden emergence of the COVID-19 pandemic in early 2020 posed an enormous threat to public health. Vaccination is currently recognized as the most cost-effective preventive and control measure against the COVID-19 pandemic worldwide and is the key to constructing a line of defense against the virus, while the epidemic prevention policies adopted by governments have an important impact on the protective behavior of the public. The purpose of this study is to analyze the mechanism by which the stringency of epidemic prevention policies affects public vaccination willingness and to explore the mediating effect of public risk perception. Methods: A cross-sectional survey was conducted among 387 adults from December 2022 to June 2023 in China. A multiple linear regression model was used to explore the impact of epidemic prevention policy stringency on public vaccination willingness, and a hierarchical regression model was used to test the mediating effect of public risk perception. Results: Our results showed that public vaccination willingness increased by approximately 45.5% for every one-unit increase in the stringency of the epidemic prevention policies, which shows that the stringency of epidemic prevention policies has a significant positive influence on public vaccination willingness. In addition, public risk perception increased by approximately 38.9% during the period of stringent government policies on epidemic prevention. For every one-unit increase in risk perception, public vaccination willingness increased by approximately 40.9%, and the relationship between the stringency of epidemic prevention policies and public vaccination willingness was partially mediated by risk perception. Conclusion: The stricter the epidemic prevention policies, the stronger the public vaccination willingness; risk perception plays a mediating effect between the stringency of epidemic prevention policies and public vaccination willingness. This finding is particularly important for exploring and analyzing the factors influencing public vaccination willingness and for improving public health.

A Big Data and FRAM-Based Model for Epidemic Risk Analysis of Infectious Diseases.

Purpose: The use of multi-source precursor data to predict the epidemic risk level would aid in the early and timely identification of the epidemic risk of infectious diseases. To achieve this, a new comprehensive big data fusion assessment method must be developed. Methods: With the help of the Functional Resonance Analysis Method (FRAM) model, this paper proposes a risk portrait for the whole process of a pandemic spreading. Using medical, human behaviour, internet and geo-meteorological data, a hierarchical multi-source dataset was developed with three function module tags, ie, Basic Risk Factors (BRF), the Spread of Epidemic Threats (SET) and Risk Influencing Factors (RIF). Results: Using the dynamic functional network diagram of the risk assessment functional module, the FRAM portrait was applied to pandemic case analysis in Wuhan in 2020. This new-format FRAM portrait model offers a potential early and rapid risk assessment method that could be applied in future acute public health events.

[Correlation between Morphological Typing and Monoclonality of Bone Marrow Plasma Cells and Its Diagnostic Value for High-Risk Smoldering Multiple Myeloma].

OBJECTIVE: To investigate the correlation between morphological typing and monoclonality of bone marrow plasma cells, and explore the diagnostic value of plasma cell morphological typing for high-risk smoldering multiple myeloma(HR-SMM). METHODS: The correlation between the morphological characteristics and the monoclonality of bone marrow plasma cells was analyzed in 84 patients with HR-SMM who treated in our hospital. The consistency of morphologically abnormal bone marrow plasma cells with serum free light chain (sFLC) ratio, next-generation sequencing (NGS) detection results, and its correlation with monoclonal plasma cells detected by flow cytometry (FCM) were further verified. The immunoglobulin types and levels of non-involved immunoglobulins in serum of the patients were detected, and the distribution of plasma cell clusters in patients with different disease was observed. RESULTS: The mean percentage of mature plasma cells were decreased successively in the order of reactive plasmacytosis (RP) group, monoclonal gammopathy of undetermined significance (MGUS) group, smoldering multiple myeloma (SMM) group, HR-SMM group and multiple myeloma (MM) group; while the mean percentage of immature, primitive, reticular and flaming plasma cells were increased successively in the order of RP group, MGUS group, SMM group, and HR-SMM group, and the difference between any two groups was statistically significant (P < 0.05).The average proportion of abnormal plasma cells in the bone marrow of HR-SMM patients was 96.2% of the total plasma cells. The proportion of abnormal plasma cells were in good agreement with the sFLC ratio and the results of NGS detection in HR-SMM patients (kappa=0.879 and kappa=0.891, both >0.75)，and showed good correlation with the monoclonal plasma cells with immunophenotype of CD45-/CD38+/CD138+/CD56+/CD19-( γ=0.825). The levels of non-involved immunoglobulin in IgG, IgA and IgM type HR-SMM patients were all decreased by more than 25% compared with the normal reference range, and the differences were statistically significant (P < 0.05). There was no significant difference in the distribution ratio of plasma cell clusters among different disease groups (P >0.05). CONCLUSION: In HR-SMM patients, the immature, primitive, reticular and flaming plasma cells in bone marrow are considered as abnormal plasma cells, and they are correlated with monoclonal plasma cells. The proportion of abnormal plasma cells in total plasma cells of bone marrow and the reduction extent of non-involved immunoglobulin level in patients have certain reference value for the diagnosis of HR-SMM.

Tobacco Quitline Callers Who Use Cannabis and Their Likelihood of Quitting Cigarette Smoking.

INTRODUCTION: Cigarette smoking continues to decline in the U.S., but cannabis use is increasing. Many people who smoke cigarettes also use cannabis. This study examines the characteristics of persons who co-use and those who do not co-use and the likelihood of quitting cigarettes for callers to Kick It California, a large state tobacco quitline. METHODS: Data were examined from Kick It California callers from January 2020 through December 2023 (N=45,151), including those from a subgroup randomly sampled and reached for evaluation at 7 months after quitline enrollment (n=3,545). The rate of cigarette smoking cessation at 7 months after enrollment for people who co-use cannabis was compared with that for people who do not. Analyses started in 2023 and concluded in January 2024. RESULTS: More than a quarter (27.2%) of Kick It California callers co-used cannabis. They were more likely to be male, to be younger, and to have a mental health condition than those who did not. Those who co-use cannabis and those who do not have similar rates of receiving quitline counseling or using Food and Drug Administration-approved cessation aids. Controlled for effects of personal characteristics and use of smoking-cessation services, people who co-use cannabis were less likely to quit cigarette smoking 7 months after enrollment (23.2% vs 28.9%; p<0.001). Among those who co-use, 42.9% intended to quit using cannabis in the next 30 days. CONCLUSIONS: A substantial percentage of tobacco quitline callers use cannabis. Those who do co-use quit cigarette smoking at a lower rate than those who do not. Over 40% of people who co-use reported intention to quit cannabis, making tobacco quitlines a rich environment to learn about people who co-use and develop strategies for intervention.

Investigating the link between gut microbiome and bone mineral density: The role of genetic factors.

Osteoporosis is a complex metabolic bone disease that severely undermines the quality of life and overall health of the elderly. While previous studies have established a close relationship between gut microbiome and host bone metabolism, the role of genetic factors has received less scrutiny. This research aims to identify potential taxa associated with various bone mineral density states, incorporating assessments of genetic factors. Fecal microbiome profiles from 605 individuals (334 females and 271 males) aged 55-65 from the Taizhou Imaging Study with osteopenia (n = 270, 170 women) or osteoporosis (n = 94, 85 women) or normal (n = 241, 79 women) were determined using shotgun metagenomic sequencing. The linear discriminant analysis was employed to identify differentially enriched taxa. Utilizing the Kyoto Encyclopedia of Genes and Genomes for annotation, functional pathway analysis was conducted to identify differentially metabolic pathways. Polygenic risk score for osteoporosis was estimated to represent genetic susceptibility to osteoporosis, followed by stratification and interaction analyses. Gut flora diversity did not show significant differences among various bone mineral groups. After multivariable adjustment, certain species, such as Clostridium leptum, Fusicatenibacter saccharivorans and Roseburia hominis, were enriched in osteoporosis patients. Statistically significant interactions between the polygenic risk score and taxa Roseburia faecis, Megasphaera elsdenii were observed (P for interaction = 0.005, 0.018, respectively). Stratified analyses revealed a significantly negative association between Roseburia faecis and bone mineral density in the low-genetic-risk group (ß = -0.045, P < 0.05), while Turicimonas muris was positively associated with bone mineral density in the high-genetic-risk group (ß = 4.177, P < 0.05) after multivariable adjustments. Functional predictions of the gut microbiome indicated an increase in pathways related to structural proteins in high-genetic-risk patients, while low-genetic-risk patients exhibited enrichment in enzyme-related pathways. This study emphasizes the association between gut microbes and bone mass, offering new insights into the interaction between genetic background and gut microbiome.

Enhanced axon outgrowth of spinal motor neurons in co-culturing with dorsal root ganglions antagonizes the growth inhibitory environment.

Introduction: Forming a bridge made of functional axons to span the lesion is essential to reconstruct the motor circuitry following spinal cord injury (SCI). Dorsal root ganglion (DRG) axons are robust in axon growth and have been proved to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. However, whether DRG transplantation affects the axon outgrowth of spinal motor neurons (SMNs) that play crucial roles in motor circuitry remains unclear. Methods: We investigated the axonal growth patterns of co-cultured DRGs and SMN aggregates (SMNAs) taking advantage of a well-designed 3D-printed in vitro system. Chondroitin sulphate proteoglycans (CSPG) induced inhibitory matrix was introduced to imitate the inhibitory environment following SCI. Axonal lengths of DRG, SMNA or DRG & SMNA cultured on the permissive or CSPG induced inhibitory matrix were measured and compared. Results: Our results indicated that under the guidance of full axonal connection generated from two opposing populations of DRGs, SMNA axons were growth-enhanced and elongated along the DRG axon bridge to distances that they could not otherwise reach. Quantitatively, the co-culture increased the SMNA axonal length by 32.1 %. Moreover, the CSPG matrix reduced the axonal length of DRGs and SMNAs by 46.2 % and 17.7 %, respectively. This inhibitory effect was antagonized by the co-culture of DRGs and SMNAs. Especially for SMNAs, they extended the axons across the CSPG-coating matrix, reached the lengths close to those of SMNAs cultured on the permissive matrix alone. Conclusions: This study deepens our understanding of axon-facilitated reconstruction of the motor circuitry. Moreover, the results support SCI treatment utilizing the enhanced outgrowth of axons to restore functional connectivity in SCI patients.

The posterolateral mid-forearm perforator flap: anatomical study and clinical application.

BACKGROUND: Defects sustained at the distal forearm are common and pedicled perforator flaps have unique advantages in resurfacing it. The purpose of this study is to reappraise the anatomy of the perforator in the posterolateral aspect of the mid-forearm and present our clinical experience on using perforator flaps based on it for reconstruction of defects in the distal forearm. METHODS: This study was divided into anatomical study and clinical application. In the anatomical study, 30 preserved upper limbs were used. Clinically, 11 patients with defects at the forearm underwent reconstruction with the posterolateral mid-forearm perforator flaps. The defects, ranging from 4.5 × 2.5 cm to 10.5 × 4.5 cm, were located at the dorsal aspect of the distal forearm in 6 cases and at the volar aspect of the distal forearm in 5 cases. RESULTS: Three patterns of the perforator were observed in the posterolateral aspect of the mid-forearm, which originated from the posterior interosseous artery, the proximal segment of the radial artery or the radial recurrent artery, and the middle segment of the radial artery, respectively. The perforator was located 11.8 ± 0.2 cm to 15.8 ± 0.4 cm inferior to the lateral humeral epicondyle. Clinically, flaps in 8 cases survived uneventfully, while the other 3 cases suffered mild marginal epidermal necrosis, which was cured with continuous dress changing. CONCLUSION: The location of the perforator at the posterolateral aspect of the mid-forearm is consistent; the posterolateral mid-forearm perforator flap is particularly suitable to cover defects in the distal one-third of the forearm.

Research on the Regulatory Mechanism of Ginseng on the Tumor Microenvironment of Colorectal Cancer based on Network Pharmacology and Bioinformatics Validation.

BACKGROUND: A network pharmacology study on the biological action of ginseng in the treatment of colorectal cancer (CRC) by regulating the tumor microenvironment (TME). OBJECTIVE: To investigate the potential mechanism of action of ginseng in the treatment of CRC by regulating TME. METHOD: This research employed network pharmacology, molecular docking techniques, and bioinformatics validation. Firstly, the active ingredients and the corresponding targets of ginseng were retrieved using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Traditional Chinese Medicine Integrated Database (TCMID), and the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan). Secondly, the targets related to CRC were retrieved using Genecards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM). Tertiary, the targets related to TME were derived from screening the GeneCards and National Center for Biotechnology Information (NCBI)-Gene. Then the common targets of ginseng, CRC, and TME were obtained by Venn diagram. Afterward, the Protein-protein interaction (PPI) network was constructed in the STRING 11.5 database, intersecting targets identified by PPI analysis were introduced into Cytoscape 3.8.2 software cytoHubba plugin, and the final determination of core targets was based on degree value. The OmicShare Tools platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets. Autodock and PyMOL were used for molecular docking verification and visual data analysis of docking results. Finally, we verified the core targets by Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases in bioinformatics. RESULTS: A total of 22 active ingredients and 202 targets were identified to be closely related to the TME of CRC. PPI network mapping identified SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 as possible core targets. Go enrichment analysis showed that it was mainly involved in T cell co-stimulation, lymphocyte co-stimulation, growth hormone response, protein input, and other biological processes; KEGG pathway analysis found 123 related signal pathways, including EGFR tyrosine kinase inhibitor resistance, chemokine signaling pathway, VEGF signaling pathway, ErbB signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, etc. The molecular docking results showed that the main chemical components of ginseng have a stable binding activity to the core targets. The results of the GEPIA database showed that the mRNA levels of PIK3R1 were significantly lowly expressed and HSP90AA1 was significantly highly expressed in CRC tissues. Analysis of the relationship between core target mRNA levels and the pathological stage of CRC showed that the levels of SRC changed significantly with the pathological stage. The HPA database results showed that the expression levels of SRC were increased in CRC tissues, while the expression of STAT3, PIK3R1, HSP90AA1, and AKT1 were decreased in CRC tissues. CONCLUSION: Ginseng may act on SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 to regulate T cell costimulation, lymphocyte costimulation, growth hormone response, protein input as a molecular mechanism regulating TME for CRC. It reflects the multi-target and multi-pathway role of ginseng in modulating TME for CRC, which provides new ideas to further reveal its pharmacological basis, mechanism of action and new drug design and development.