Previous research proposed that ligament laxity is a clinical feature that can be easily overlooked in patients with adolescent idiopathic scoliosis (AIS). Relaxin and relaxin-related peptides, which have anti-fibrosis roles in the vascular and kidney system and relax the pubic symphysis during pregnancy, may contribute to ligament laxity. The goal of this research was to evaluate the role of in AIS. We found significantly increased relaxin-3 plasma in patients with AIS, as well as a significant correlation between joint hypermobility and relaxin 3 plasma levels. In a classic mouse model (C57BL/6J) of scoliosis, which was established according to the literature, showed significantly higher relaxin-3 plasma levels compared to normal group. In the relaxin-3 knockout C57BL/6J mice model the prevalence of scoliosis was significantly decreased. An in vitro experiment showed that relaxin 3 has anti-fibrotic effects on spinal ligament fibroblasts in both humans and mice by inhibiting TGF-β via relaxin family peptide receptor 3 (RXFP3) and increasing expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 via the TGF-β/Smad2 and MAPK-ERK1/2 pathway. Blocking RXFP3 function with R3(B1-22)R significantly decreased the prevalence of scoliosis in C57BL/6J mice. In summary, the anti-fibrotic effects of relaxin-3 and RXFP3 activation may aggravate the pathogenesis of AIS.

The mammary glands are closely related to the female reproductive system. Due to various factors including increased survival of patients with breast cancer (BC), there is an increased probability of developing additional primary gynecologic cancers such as ovarian cancer (OC), endometrial cancer (EC), and cervical cancer (CC). Multiple primary cancers (MPCs) refer to two or more different primary malignancies occurring in the same or different organs in the same patient. This review discusses the common types of BC-associated MPCs, namely, BC associated with OC, EC, or CC, as well as risk factors, clinical classifications, pathology, treatment, and prognosis.

Introduction: Cor triatriatum sinister (CTS) is a rare congenital heart defect associated with atrial fibrillation (AF). The incidence of hemodynamically insignificant CTS in the AF ablation population and its effect on ablation success are not known. Furthermore, little is known about the potential effect of CTS on arrhythmogenic substrate. Objective: We define the incidence of hemodynamically insignificant CTS in patients undergoing AF ablation with RF and cryoballoon ablation, the technical challenges created by the left atrial partitioning, and the potentially arrhythmogenic effects of the membrane. Methods: First-time AF ablation cases at our institution over a 10-year period were screened to identify and describe patients with CTS. Additionally, a PubMed/MEDLINE search was performed for a review of literature on patients with CTS undergoing CA of AF. Results: Of the 3,953 consecutive patients undergoing initial AF ablation during the study period, four patients (0.10%) had CTS. Ablation was successful acutely in all patients. One patient had recurrent AF and required repeat ablation for a single procedure success rate of 75% and multi-procedure success rate of 100%. The CTS membrane was associated with low voltage zones in the two patients in whom it was measured and with substrate for macro-reentrant atrial tachycardia in one of these patients. Conclusion: The incidence of hemodynamically insignificant CTS in patients undergoing CA for AF is very low, but does not serve as a significant barrier to successful ablation as long as pulmonary vein access is approached by directed access to the superoposterior chamber.

Apart from its contribution to climate change, offshore oil and gas extraction is also a potential threat to the diversity and function of marine ecosystems. Routine monitoring of the environmental status of affected areas is therefore critical for proper management. While current morphology-based monitoring is relatively time-consuming, costly and prone to identification bias, environmental DNA metabarcoding offers an attractive alternative, including for impacts of oil drilling, extraction or spills. However, to be ready for routine monitoring, its performance needs to be demonstrated, through agreement with assessments based on physicochemical measurements and current bioindicators. To this end, we applied metabarcoding to sequence the metazoan and total eukaryotic benthic components. We targeted an range of sites, from high to low impacts, located near active production platforms and reference sites, in the North and Barents Seas. Alpha diversity and community structure of both datasets correlated strongly with a physicochemical pressure index (PI), based on total hydrocarbons, PAH16, Ba and Cu. The macroinvertebrate-based Norwegian Sensitivity Index (NSI) based on the COI metabarcoding data also agreed well with morpho-taxonomy based values, and with PI. Further, we identified a set of bioindicator taxa from both metabarcoding datasets, to develop novel biotic indices and demonstrate their predictive performance using cross-validation. Finally, we compared co-occurrence networks from impacted v less disturbed sites, to improve the understanding of the ecological consequences of impacts. Our study demonstrates that metabarcoding is comparable to the morpho-taxonomic approach in terms of accuracy, and could eventually be used to replace it, given further efforts.

It is a new attempt to investigate thermal stability and reactivity of four 3-Phenyl-2-propene compounds by MCPVT. The temperature of initial oxygen absorption (Ta) and rapid oxidation(TR) were calculated. Results showed that four 3-Phenyl-2-propene compounds were stable under nitrogen atmosphere. The Ta of cinnamaldehyde, cinnamyl alcohol, β-methylstyrene and cinnamic acid were 271.25K, 292.375K, 323.125K, and 363.875K, and the TR of cinnamaldehyde, cinnamyl alcohol, β-methylstyrene and cinnamic acid were 301.125K, 332.75K, 357.91K, and 385.375K, respectively. The oxidation reactivity order was derived: cinnamaldehyde > cinnamyl alcohol > β-Methylstyrene > cinnamic acid. The oxidation kinetics of four 3-Phenyl-2-propene compounds was calculated, which showed a second-order reaction. Peroxide concentrations of initial oxidation were determined by iodimetry, and the oxidation products were analyzed by gas chromatography-mass spectrometry (GC-MS). Results showed peroxides were generated. According to the complex oxidation products, important insights into the pathways of oxidation were provided.

Aim: We aimed to investigate the correlation of acute flank pain incidence with number of pregnancies and hydronephrosis. Material and method: Forty-eight patients admitted with acute flank pain have been included in this study. Patients with urinary tract infection, abnormal urinalysis, kidney or ureteric stone have been excluded. Twenty-four were nulliparous and the remaining pregnancies were multiparous. All patients had urinary ultrasound (US) by the same radiologist. Visual analogue scale (VAS) was used. All the patients had conservative management firstly. same radiologist. Visual analogue scale (VAS) was used when patients admitted to the hospital. All the patients had intravenous fluid therapy as conservative management, paracetamol as analgesic treatment and oral nitrofurantoin as antibiotherapy. Patients who did not benefit from conservative treatment had ureteral JJ stent placement. Results: Nulliparous pregnant were younger and had earlier gestational weeks (25.1±3.7 – 28.7±3.8 p=0.004 and 22,9±3.7 – 26.3±4.0 p=0.005), but higher VAS scores. In the nulliparous pregnant women, a significant, medium level positive correlation was found between the degree of hydronephrosis and the VAS scores. It was observed that the higher the hydronephrosis, the higher the VAS scores were. On the other hand, in multiparous pregnant women, no correlation was detected between the degree of hydronephrosis and the VAS scores. In comparison of two groups in relation to BM, hydronephrosis degree, hydronephrosis side, serum creatinine levels, type and side of pain, no significant difference was identified. Forty-two percent of patients described a colic pain. While 91.7% of the patients benefitted from conservative treatment, 4 patients had JJ stent insertion. Conclusion: This study demonstrates that there is a correlation between acute flank pain and hydronephrosis and that the degree of hydronephrosis increases as the pain intensifies, especially in the nulliparous, such correlation is stronger. Keywords: Pregnancy, hydronephrosis, acute flank pain, nulliparous, multiparous

Aims of the study: We aimed to investigate the effects of TAS2R38 (bitter taste gene) and TAS1R2 (sweet taste gene) gene polymorphisms, which are the most important members of the Tat gene family, on the dental status of obese and normal-weight children. Methods used to conduct the study: The study included 78 healthy children and 100 children diagnosed with obesity (5 - 16 years old). Anthropometric measurements and the dental status of the children were evaluated. The DMFT/dmft index of teeth was determined, using standards methods recommended by world health organization. Blood samples were collected from all subjects and were analyzed via PCR using specific primers for the genetic analyses. Five single nucleotide polymorphisms (SNPs) indicating TAS2R38 gene and TAS1R2 polymorphisms were investigated. Truncate poisson and truncate negative binomial modeling approach used with the data. Results of the study: DMFT score was low in obese children and it was high in children who doesn’t sense bitter taste (non-taster). While obese non-taster children had increased DMFT scores, normal weighted non-taster children had decreased DMFT scores. Conclusions drawn from the study and clinical implications: The alanine, valine, and isoleucine (AVI), as well as the proline, alanine, and valine haplotypes (PAV), of the TAS2R38 gene are associated with DMFT score and obesity. What’s Now: It is known that the sense of taste affects nutrition. Moreover, nutrition is associated with caries and obesity. What’s New: The authors studied caries and obesity along with taste genes in this study. There are little studies in the literature that study obesity, decay and taste genetics together, and this study clarifies this issue in three ways. At the same time, an effort was given to the statistical analysis part Keywords: Oral health, childhood obesity, tooth decay, TAS2R38 polymorphism, diet, genetic

Purpose: Magnetic Resonance-High Intensity Focused Ultrasound (MR-HIFU) has revolutionized the treatment of Uterine fibroids. Usually, they are associated with prolonged heavy bleeding during the menstrual period, sacral pain, and increased frequency of UTIs, secondary dysmenorrhea, constipation, and pregnancy-associated problems. It also impacts usual activities, which lead to diminished quality of life and rising healthcare costs. Generally, surgery is the only choice for uterine fibroids; however, MR-HIFU is an entirely non-invasive novel therapy, preferred in pregnancy desiring females. Excluding trials with stringent treatment protocols that are no longer used, the efficacy of Magnetic Resonance-High Intensity Focused Ultrasound (MRHIFU) therapy for uterine fibroids is being re-evaluated. Methods: RCTs, Prospective or Retrospective non-randomized, and cross-over studies that considered clinically symptomatic uterine fibroid treatment were included. The author has searched the data in Cochrane Library, PubMed/MEDLINE, SCOPUS, EMBASE databases. Meta-Analysis was performed using NCSS software, and data were analyzed at a 95% confidence level with a level of precision at 0.05. The NPV%, tSSS change%, and QoL were computed. Meta-Regression was done to evaluate the association between the different parameters. Results: The overall effect of NPV% was 70.24, where the 95% confidence interval ranged from 61.9% to 78.16%. The overall impact of tSSS% change is near 50% after the follow-up of 3 months, 6 months, and 12 months in the included studies. There was a significant improvement in the health-related quality of life (Hr-QoL). Conclusion: The efficacy of MR-HIFU therapy was improved as treatment protocols aimed for total ablation. On the other hand, regulated studies are required to determine the function of MR-HIFU in the treatment of uterine fibroids.

Forestation actions are a major tool for both climate-change mitigation and biodiversity conservation, which are often considered independently. In either case, little attention is given to the potential of the vast drylands, and the albedo warming effect associated with such forestation efforts. We propose an approach to identify suitable land for forestation and quantify its ‘net equivalent carbon stock change’ over 80 years of forests lifetime (Ceq-80), accounting for both carbon sequestration and albedo changes. Applying it over Queensland as a test case shows that albedo effects reduce the carbon sequestration cooling effects by >50%, with residual Ceq-80 of 0.72 Gt, equivalent to 15% of the state’s projected carbon emissions for the same time. Our methodology extends restoration efforts by identifying new land for forestation and demonstrates the importance of quantifying the climatic value of forestation in drylands, which must also be considered in biodiversity conservation efforts.

Abstract Objective To evaluate the effects of number and quality of transferred blastocysts and female age on pregnancy outcomes. Design A retrospective study. Setting Two IVF centers. Population Women undergoing first blastocyst transfer in frozen-thawed cycles. Methods 6096 frozen-thawed blastocyst transfer cycles were divided into five groups based on blastocyst number and quality and three groups according to female age. Main Outcome Measures Implantation rate (IR), clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), live birth rate (LBR) and neonatal characteristics. Results Female age, quality and number of transferred blastocysts had significant effects on pregnancy outcomes. IR, CPR and LBR of the same blastocyst transfer groups decreased gradually with age. Increasing the transferred number of same grade blastocysts did not obviously increase CPR and LBR, however, it significantly increased MPR. For double blastocyst transfer, the better-quality the transferred blastocysts were, the higher the IR, CPR, MPR and LBR were. Singleton group had the best neonatal characteristics followed by dizygotic twins and monozygotic twins. There was a positive correlation between sex ratio and the proportion of good-quality blastocysts, and the difference was significant between good-quality and poor-quality blastocyst groups (1.35 vs 0.98, P/CI = 0.002/1.123-1.687). Conclusions Selective single good-quality blastocyst transfer may serve as an effective embryo transfer strategy to reduce MPR while maintaining LBR and obtain good pregnancy outcomes, but, the strategy may result in an unbalanced sex ratio of newborns. Funding None. Keywords: Blastocyst transfer, age, multiple pregnancy, live birth rate, neonatal characteristics.

In this paper, we consider the existence and concentration of positive solutions of the Kirchhoff-type problem \[ \left\{ \begin{array} [c]{ll}% -\left(a+b\int_{\mathbb{R}^3}|\nabla u|^2dx\right)\Delta u+\lambda V(x)u=f(x,u)\text{,} & \text{in }\mathbb{R}^{3}\text{,}\\ u>0~~~~\text{in }\mathbb{R}^{3}~~~~u\in H^1(\mathbb{R}^3)\text{,}% \end{array} % \right. \] where $a,b>0$ are constants, $\lambda>0$ is a parameter. Under some suitable assumptions on $V$ and $f$, the existence and concentration of positive solutions is obtained by using variational methods.

Objective: To review our experiences of descending necrotizing mediastinitis (DNM) secondary to deep neck infection (DNI) and determine appropriate airway management for decreasing mortality and morbidity of patients with DNM. Study Design: A retrospective study Subjects and Methods: Medical records of 20 patients (8 women and 12 men) who had been managed for DNM secondary to DNI between March 2006 and December 2019 were analyzed. Diagnosis and extent of infection were confirmed by computed tomography of the neck and chest. The upper airway was closely monitored with a fiberoptic laryngoscope. Complications were evaluated according to various types of airway management in our serial cases. Results: Five (25 %) out of 20 patients died as a result of septic shock and multi-organ failure. None of these patients died from accidental airway obstruction or airway management mishaps. Keeping short-term orotracheal intubation was safe and adequate after the initial surgery. Early tracheotomy was performed for four patients of all but it was significantly associated with mortality (p=0.032). Three patients who underwent late tracheotomy had no mortality. Patients with tracheotomy had longer duration of overall hospital stay than those without tracheotomy. Conclusions. Well-controlled airway management might decrease mortality, hospitalization, and airway complications in patients with DNM secondary to DNI. Keeping orotracheal intubation rather than upfront tracheotomy should be first considered when managing airway along with examination of the upper airway with a fiberoptic laryngoscope.

Background: The personal protective equipment (PPE) and frequent hand hygiene procedures needed during the COVID-19 outbreak impair skin integrity in healthcare workers (HCWs). We aimed to evaluate the prevalence and risk factors of adverse skin reactions related to infection-prevention measures among HCWs. Methods: A questionnaire survey was administered to evaluate the duration of PPE, disinfectant, and moisturizing agent use, as well as handwashing frequency among our hospital’s HCWs. Results: The questionnaire was completed by 702 HCWs with a mean age of 34.8±9.8 years. Adverse skin reactions were reported by 79.5% of our participants. Hands (63.5%) and face (48.9%) were the most commonly affected areas. Female sex, being a doctor/nurse, having a history of underlying chronic dermatoses, and PPE usage more than six hours per day were increased the risk of adverse skin reactions. Handwashing more than 10 times/day and moisturizing less than 5 times/day were also related to increased adverse skin reactions. In HCWs, wearing more than one mask was associated with pressure-induced skin changes on the face and triggering herpes labialis. Conclusion: Hand hygiene-associated dermatitis is triggered by frequent handwashing and less moisturizing among HCWs. Surgical masks may also be just as responsible as N95 masks for causing facial skin damage.

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Introduction: PDL1 and its interaction with PD1 is implicated in immune dysfunction in TB and HIV. The expression of PDL1 on multiple subsets of monocytes as well as their associations with cytokines and microbial products have not been well studies. Method HIV (n=35), TB (n=34) and TBHIV co-infected patients (n=12), primarily treatment naïve and apparently healthy controls (n=39) were recruited. Monocyte subsets were evaluated for PDL1 expression by flow cytometry; plasma TNFα, IL6, IP10, IL10 were measured by Luminex; and cytokine mRNA from purified monocytes quantitated by qPCR. The association of PDL1 with cytokines, clinical and microbial indices, including HIV viral load, TB smear microscopy and TB urinary lipoarabinomannan (LAM) were assessed. Results: Monocyte expression of PDL1 was significantly higher in TB, HIV and TBHIV co-infected patients compared with healthy controls (p=0.0001), with the highest levels in TBHIV co-infected patients. The highest expresser of PDL1 was intermediate (CD14+CD16+) monocytes in all participant groups. PDL1 moderately correlated with viral load and smear positivity in HIV and TB respectively, whereas weakly with LAM in TBHIV co-infection. PDL1 levels strongly correlated with plasma TNFα, IL6, IP10 and IL10 level in TB subjects, and TNFα and IP10 in HIV patients. However, cytokine mRNA from purified monocytes showed no association with either plasma cytokines or monocyte PDL1, implying that if cytokines modulate PDL1, there are likely not originating from circulating monocytes themselves. These results underscore the importance of further characterization of multiple monocyte subsets and their phenotypic and functional differences in different disease states.

As an important ruminant on the Qinghai-Tibet Plateau, Tibetan sheep can maintain their population reproduction rate in the harsh high-altitude environment of low temperature and low oxygen, which is related to their special adaptations to the plateau. Microbes (known as “second genomes”) play an important role in the host adaptations. However, there have been no reports on the effects of the interactions among rumen fermentation, the microbiota, and host gene expression on the adaptation of Tibetan sheep to high altitude. In this study, rumen fermentation characteristics, the microbiota, and rumen epithelial gene expression of Tibetan sheep in various months were analyzed. The results show that the rumen fermentation characteristics of Tibetan sheep differed in different months. The total SCFA, acetate, propionate, and butyrate concentrations were highest in Oct and lowest in Jun. The CL activity was highest in Feb, while the ACX activity was highest in Apr. In addition, the diversity and abundance of rumen microbes differed in different months. Bacteroidetes (53.4%) and Firmicutes (27.4%) were the dominant phyla. Prevotella_1 and Rikenellaceae_RC9_gut_group were the dominant genera. The abundance of Prevotella_1 was highest in Jun (27.8%) and lowest in Dec (17.8%). In addition, the expression of CLAUDIN4 and ZO1 was significantly higher in Apr than in Aug and Dec, while the expression of SGLT1 was highest in Aug. Correlation analysis showed that there were interactions among rumen fermentation characteristics, the microbiota, and host gene expression, and the host adjusted the rumen fermentation and microbiota structure according to changes in ambient temperature, to adapt to the plateau environment.

Background: LAB are important probiotics and are considered safe food-grade microorganisms. With the continuous in-depth study of LAB, which was discovered that LAB are faces various environmental pressure phenomena in applications. These stressful environments will obviously worsen the physiological condition of LAB, which in turn will affect the production of their fermentation and metabolites. Purpose: In order to realize the industrialization of cheap biological raw materials and reduce the cost of raw materials. Based on biomass resources, the economical fermentation processes have become a research focus. Summary: This article reviews the application status of cheap raw materials in LAB, focusing on the development of biomass resources based on LAB fermentation. discusses the bottlenecks in the production and metabolism of LAB, and prospects the development of LAB. Conclusion: It provides a theoretical basis for the construction of process engineering technology and metabolic regulation. In addition, the use of modern biotechnology strategies to screen target strains needed to increase LA production was also discussed, such as adaptive evolution.

In light of the current pandemic, the Corona pandemic, researchers are making a great effort to try to understand and appreciate the characteristics of the SARS-CoV-2 epidemic in order to prevent its spread. It was founded that the virus is increasing in many regions and countries that have achieved clear success in combating environmental pollution or that are not exposed to dusty storm, and infections are increasing again in the same country with different densities of sick people according to the weather temperature and windy season. Three important countries have been taken as case studies, such as Italy, China and Iran. it was found that the regions that are exposed to dust currents are less spreading of the coronavirus. This due to the dust is almost contain 90 % of metal oxide that act as nature photocatalysts for O●-2 and ●OH production. This oxidizing spices are capable to destroy SARS-Cov-2.

Colorectal cancer is one of the deadliest cancers, and the discovery of new diagnostic biomarkers and therapeutic targets is vital. Interleukin-36α (IL-36α) is a proinflammatory factor that can initiate the inflammatory response and promote the systemic T helper-1 (Th1) immune response. In this study, we investigated the immunological role of IL-36α in CRC. We found that IL-36α was downregulated in human CRC tissues. Patients with high IL-36α levels showed better survival and low IL-36α expression was significantly associated with greater tumor distal metastasis and TNM stage. We constructed two cell lines overexpressing IL-36α (CT26-IL-36α and HT29-IL-36α cells). In vitro assays revealed that IL-36α overexpression reduced the proliferation, migration, and invasion of CT26-IL-36α, and HT29-IL-36α cells. Using CT26-vector and CT26-IL-36α tumor xenograft and lung metastasis models, we found that IL-36α overexpression elicited a significant antitumor effect and inhibited lung metastasis in vivo. These inhibitory effects were associated with an increase in the number of CD3+CD8+ T lymphocytes within the tumor tissue as well as increased cytokine production in CD8+ T lymphocytes present in the tumor, spleen, and draining lymph nodes. Furthermore, we revealed that CT26-IL-36α cells enhanced the secretion of CXCL10 and CXCL11 from chemotactic CD8+ T lymphocytes, as compared with CT26-vector cells. Taken together, these results suggest that IL-36α is a promising therapeutic agent for targeting CRC by promoting the activation, proliferation, and tumor infiltration of T lymphocytes.

Stage-structured population models parameterized from benchtop trials of individual growth, reproduction and survival predicted that temperature rise should make populations of Daphnia magna more resilient to periodic harvest perturbation, despite reduced stock abundance. We tested these predictions under controlled laboratory conditions on 24 populations maintained under constant levels of food abundance, but subjected to weekly harvest events over 10 weeks. As predicted, unperturbed Daphnia populations raised at 15◦C were substantially more abundant by the end of 10 week trials than those raised at 25◦C, but abundance declined sharply with harvest intensity and Daphnia populations collapsed entirely at the highest harvest rate, whereas those populations raised at 25◦C were little affected by perturbation. Our findings suggest that projected patterns of climate change should tend to make populations whose growth rates and rate of maturation increase with temperature better capable of coping with periodic harvest perturbation, despite declining levels of abundance.

Background: The present meta-analysis was carried out to assess the risk of infection and other side effects after anti TNF- α use to treat Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. Methods: To assess the impact of anti-TNF medicines on the prevalence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection; risk of cancer), we performed a meta-analysis. We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 27 articles were used for the data analysis. The risk of bias (RoB) in included studies was evaluated using the QUADAS-2 tool. The odds ratio of these studies was used to construct the forest plot. The random-effects model was used to pool the data. Also, the random-effects model was used with statistical significance at a p-value less than 0.05 to assess the risk of infections and cancer after anti-TNF treatment. Results: The risk of developing cancer (OR=1.13; 95% CI 0.79 to 1.62; p<0.05) which is lesser than serious infections (OR= 1.5; 95% CI 1.0257 to 2.2276; p<0.05) after anti TNF treatment. However, the risk of developing tuberculosis infection is highest in the patients on anti-TNF treatment (OR=3.96; 95% CI 2.87-5.45) followed by skin and soft tissue infections, i.e. (OR= 2.4598; 95% CI 1.0481 to 5.7732; p<0.05). Conclusion: With the growing use of TNF inhibitors in adult patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, it is critical to keep track of their safety profiles using additional resources (e.g., registries and long-term epidemiological studies). The present meta-analysis is recent evidence which suggests that there is a definite high risk of tuberculosis and cancer after anti-TNF treatment.

The innate immune system recognizes conserved features of viral and microbial pathogens via pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are one type of PRRs used by the innate immune system to mediate the secretion of pro-inflammatory cytokines and promote innate and adaptive immune responses. TLR family members TLR7 and TLR8 (refer as TLR7/8 subsequent) are endosomal transmembrane receptors that recognize purine-rich single-stranded RNA and bacterial DNA and thereby elicit an immunologic reaction to pathogens. TLR7/8 have been demonstrated to mediate pro-inflammatory cytokine secretion by activating immune cells. Accumulating evidence indicate that TLR7/8 are closely related to numerous immune-mediated disorders, specifically cancers, autoimmune diseases, and viral diseases. The TLR7/8 agonists and antagonist used as drugs or adjuvants have been well identified in preclinical studies and clinical trials as promising immunostimulators for the immunotherapy of these immune-mediated disorders. These achievements are a good reason for humans to open new doors for exploring immunotherapy of immune-mediated disorders. Nevertheless, many needs remain unmet, and their therapeutic effects are poor, and always cause strong immune-related toxicities. In this mini review, we present an overview of the TLR family members, particularly TLR7/8, and address the underlying molecular mechanisms and clinical implications of TLR7/8 in immune-mediated disorders.

Partial anomalous pulmonary venous connection is a rare adult congenital heart disease that leads to an anatomical lefttoright shunt. Right superior pulmonary vein and azygos vein open to the superior vena cava, with atrial septal defect and severe pulmonary hypertension are also rare congenital anomalies that result in right-to-left shunt. A 52yearold male presented with dyspnea on exertion and fatigue. He was further diagnosed in our hospital and was found to have the aforementioned congenital abnormalities, causing a bidirectional shunt. On further investigation, he was found to have hypoxemia on oximetry. The patient was treated via surgical corrections of the congenital anomalies, but still showed persistent hypoxemia after the operation. After the related diseases were excluded through various examinations, we finally thought that hypoxemia was probably caused by pulmonary hypertension.

Restrictive mitral valve annuloplasty is the worldwide used technique to treat secondary mitral valve regurgitation. This procedure is still associated with high rate of recurrent mitral valve regurgitation at 1 year follow-up. In the last 2 decades, several investigators proposed different surgical techniques to add to mitral valve annuloplasty to improve the long-term repair results in secondary mitral valve regurgitation. Papillary muscle (PPM) relocation technique aimed to reduce the distance between the head of PPM and the mitral annulus to relieve leaflets tethering and improve coaptation. Chordal cutting procedure consist in cutting a limited number of basal chordae to improve systolic leaflet motion and coaptation and reduce leaflets tethering; eliminating secondary chordae in the anterior leaflet can allow the leaflets to assume a more normal and less taut configuration, with more effective coaptation at their free margin. Chordal cutting and transfer procedure was proposed to maintain the continuity between the mitral apparatus and the left ventricle. PPM sling or approximation technique is performed using prolene suture reinforced with pleagets to joint bot papillary muscles; this technique reduce the muscles displacement and improve systolic coaptation. Several papers showed the superiority of the adjunction subannular procedure up to isolated restrictive annuloplasty in term of outcomes .