To clarify influence of catgut embedding plus warm needle moxibustion on improving inflammation and quality of life of knee osteoarthritis patients.  The data of 120 patients with knee osteoarthritis admitted to our hospital from June 2018 to June 2021 were used for retrospective analysis. Patients were divided into control group and observation group in a random manner, with 60 cases each. The control group was orally administrated with one diclofenac sodium sustained-release tablet (100 mg) once a day, for 8 courses with 7 days for each course. The observation group underwent catgut embedding plus warm needle moxibustion. P < 0.05). Quality of life scores presented elevation after treatment and were higher in observation group than control group (P < 0.05). Curative efficacy presented no difference between two groups (P > 0.05), while clinical cure rate was higher in observation group than control group .  The Western Ontario and McMaster Universities Arthritis Index and gonitis Lequesne scores in two groups were decreased after treatment and were lower in observation group than control group ( Warm needle moxibustion plus functional exercise can effectively improve clinical symptoms of knee osteoarthritis patients, and improve their knee joint function and inflammatory response. Knee osteoarthritis (KOA) is a degenerative disease characterized by knee cartilage degeneration and reactive hyperplasia , which iInner Canon of Huangdi. The TCM believes that this disease is mostly caused by liver and kidney deficiency, invasion by external pathogens, and consumptive wear and tear. The main treatment methods of TCM for this disease include oral administration, external application, fumigation, acupuncture, and massage. Each treatment method can be used alone or cooperated with each other to reduce swelling, relieve pain, and improve joint function. Furthermore, TCM treatment has the advantages of convenience, less side effects, easy promotion, relatively small economic burden, etc., and is easily accepted by patients [In traditional Chinese medicine (TCM), KOA belongs to the category of “rheumatism”, which is recorded in the patients . Acupoinpatients . Catgut patients .In our research, we aimed to investigate the efficacy of catgut embedding combined with warm needle moxibustion on KOA, and to clarify its impact on quality of life of patients.Guidelines for the Diagnosis and Treatment of Osteoarthritis (2017 version); (2) KOA grade: II-IV; (3) those who did not receive other treatments within 1 month. Exclusion criteria: (1) those complicated with severe cardiovascular and cerebrovascular, liver, and renal system diseases; (2) those complicated with rheumatoid arthritis, septic arthritis, meniscus injury, joint tuberculosis, and other knee joint diseases; (3) those with blood diseases, mental disorders, and malignant tumors; (4) those with allergic constitution. Age, disease duration, KOA grade, and other data of KOA patients presented no difference but balance between two groups (P > 0.05). This study was approved by the Ethics Committee of Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, and all patients signed informed consent.The data of 120 patients with KOA admitted to our hospital from June 2018 to June 2021 were chosen for retrospective analysis and divided into two groups in a random manner. There were 60 cases in control group, including 32 males and 28 females; the age was 41-70 years, average: 59.52 ± 9.45 years, the disease duration was 0.5-10 years, average: 5.57 ± 1.38 years. There were 60 cases in observation group, including 34 males and 26 females; the age was 40-69 years, average: 58.05 ± 9.12 years, the disease duration was 0.5-10 years, average: 5.65 ± 1.42 years. Inclusion criteria: (1) meet the relevant diagnostic criteria in the The control group was administrated conventional nonsteroidal anti-inflammatory drugs , and ourThe observation group underwent catgut embedding plus warm needle moxibustion therapy. The patients were given warm needle moxibustion and acupoints such as the inner and outer knee eyes, Yanglingquan, Yinlingquan, Liangqiu, and Zusanli were chosen on the affected side. Routine disinfection of the skin, oblique puncturing of the inner and outer knees and inwards, straight puncturing in Yanglingquan, Yinlingquan, Liangqiu, and Zusanli, retention of the needles for 30 min after obtaining Qi, moxibustion in Liangqiu and Zusanli for 2 puncture/time, 1 time/d. Catgut embedding acupoints: Xuehai, Liangqiu, Yanglingquan, Ashi, popliteus point, and goose foot point. The patients took the supine position, with the knee joint fully exposed, the joint was flexed 30°-45°, and the back of the knee joint was bolstered. The operator stood on the affected side, operated in strict accordance with the surgical aseptic principle, and disinfected the skin with an iodophor cotton ball, and the disinfection area was supposed to include a range of 10 cm around the acupoint. The skin was disinfected from the acupoints to the peripheral skin three times in total, and then wiped with an alcohol cotton ball to remove the iodine on the skin surface. The catgut embedding needle-knife was taken out, the polyglycolide absorbable thread package  was opened with sterile scissors, the operator wore sterile gloves, and gently pulled the needle core handle of catgut embedding needle-knife back. The absorbable catgut was taken out with sterile tweezers, the catgut embedding needle-knife was inserted with a length of 0.75 cm, and the catgut was bent into a V shape. The thumb of the left hand was used to determine the acupoint again, the index finger and middle finger of the left hand were used to tighten the skin around the acupoint, and the catgut embedding needle-knife was pressed against the skin of the acupoint with the right hand. The direction of the blade was parallel to the longitudinal axis of the lower limb. After quickly piercing the skin, the needle was inserted slowly, with depth of 1.5 cm  and avoided entering the joint cavity. The needle knife was used to cut the local tissue longitudinally and rotated several times. When the needle felt loose, the needle handle was pushed down, the catgut was buried into the acupoint, the needle was slowly pulled out, and the acupoint was pressed at the same time. When there was no blood oozing out of the skin, the same method was used to puncture other acupoints on the front of the knee joint, and a sterile patch was applied after the puncture was completed. The patients were changed to the prone position to fully expose the acupoints behind the knee joint. After the operator changed sterile gloves, the same method was used to sterilize acupuncture at a fixed point. After the operation, the dressing was changed once a day for the first three days, and then every two days to avoid infection, once every 2 weeks, 4 weeks as a course of treatment, with continuous treatment for 2 courses. The patients in both groups were given standardized health guidance and performed functional exercises of the knee joint.Adverse events were defined as unanticipated and unanticipated signs, symptoms, and diseases that occurred after treatment during the course of this clinical study and were not necessarily caused by this clinical study. Subjects were suspended from trial treatment if a serious adverse event (SAE) occurred during the course of the study, and their participation was discontinued if continued treatment was considered dangerous to the subject and the adverse event was related to the intervention.All participants had the right to withdraw from the study at any time. If the subject refuses to continue, withdraws consent, or violates inclusion or exclusion criteria, participation will end at any stage. In addition, the investigators recorded the completion of the study and the reasons for stopping the trial.The KOS self-assessment scale was used to evaluate the condition. The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index mainly evaluated from three aspects: pain degree, stiffness degree, and difficulty in performing daily activities . It inclLequesne score for osteoarthritis  was mainα (TNF-α) levels in two groups before treatment, and after 2 courses of treatment were assessed by ELISA kit MMP-3, MMP-9, interleukin-1 (IL-1), and tumor necrosis factor-The health survey short-form MOS SF-36 evaluated quality of life , includiEfficacy Criteria for Diagnosis of Diseases in Traditional Chinese Medicine, clinical efficacy was classified into 4 grades: clinical cure , markedly effective , improved , and ineffective Referring to the x ± s), independent samples t-test was used for comparison between groups, and paired sample t-test was used for both within groups. Enumeration data were expressed as rate (%), and x2 test was used for comparison between groups. P < 0.05 meant there was statistical significance.SPSS 20.0 software was used for data analysis. Measurement data were expressed as (P > 0.05). WOMAC scores and total scores in two groups after treatment presented depletion relative to those before treatment, with statistical significance (P < 0.05). WOMAC scores and total scores in treatment group presented depletion relative to control group after treatment, with statistical significance . Relative to control group, serum MMP-3, MMP-9, IL-1, and TNF-α levels in observation group presented depletion after 1 month of treatment . After treatment, quality of life scores of each dimension and total scores presented elevation relative to those before treatment, and observation group presented elevation relative to control group, with statistical significance , which was comparable. Gonitis Lequesne scores in two groups after treatment presented depletion relative to those before treatment, with statistical significance (P < 0.001). Gonitis Lequesne scores in observation group presented depletion relative to control group, with statistical significance , but clinical cure rate in observation group presented elevation relative to control group, with statistical significance  needles are used to clear the nine orifices and remove the evil energy between the three hundred and sixty-five festivals in the whole body. This is called different needles have different functions and indications.” It is suggested that the use of acupuncture to release and decompress the soft tissues such as joint capsule and fascia of the whole body can achieve the purpose of curing pain with looseness. Acupuncture can release scars and soft tissue adhesions, protect articular cartilage cells, and maintain mechanical balance, which is a commonly used clinical treatment method [Miraculous Pivot: Beginning and End pointed out: “Those who have been ill for a long time will have deep penetration of pathogens. For such chronic diseases, deep acupuncture is required, and the needles are kept for a long time.” Acupoint catgut embedding can achieve continuous stimulation locally, and at the same time, it reduces the possible adverse reactions of long-term acupuncture to local tissues, and has the characteristics of “replacing the thread with needles.” Catgut embedding plus warm needle moxibustion combines traditional acupuncture and acupoint thread embedding, and has both the relaxing effect of traditional warm needle moxibustion and the continuous stimulation of acupoint thread embedding. The therapeutic effect is better than that of warm needle moxibustion or acupoint catgut embedding alone. Relative to warm needle moxibustion, it has the advantages of high stimulation intensity and long duration of curative efficacy. Our research will provide a clinical basis for exploring the effectiveness of catgut embedding plus warm needle moxibustion by observing the efficacy of catgut embedding plus warm needle moxibustion on KOA.Catgut embedding plus warm needle moxibustion is a new treatment method developed from traditional acupuncture and acupoint thread embedding. t method , 16. TheThe WOMAC scores can effectively reflect the patient's condition before and after treatment, such as the patient's satisfaction. It has a high reliability in the assessment of KOA . Herein,α can promote the formation of new blood vessels in the synovium, elevate the permeability of vascular wall, and aggravate inflammatory response of joints. Angiopoietin I can promote angiogenesis and stimulate synovial and cartilage lesions [α indicate that patients' bone and cartilage structures are being destroyed. Herein, after 1 month of treatment, relative to control group, serum MMP-3, MMP-9, IL-1, and TNF-α level in observation group presented depletion, suggesting that catgut embedding plus warm needle moxibustion can effectively reduce osteoarthritis in elderly patients.Inflammatory cytokines exert a vital role in KOA occurrence and development. Inflammatory cytokines stimulate synovial cells to secrete massive IL-1, promote the synthesis of MMP-3, and MMP-9, and further degrade articular cartilage, affecting bone metabolism . TNF-α c lesions . The eleMoreover, similar to control group, pain, knee joint function, and quality of life of patients in treatment group were also remarkably improved relative to those before treatment, but improvement in observation group was more marked. Though curative efficacy presented no difference between two groups, clinical cure proportion in observation group presented elevation relative to control group, suggesting that catgut embedding plus warm needle moxibustion in treating KOA may further optimize the curative efficacy and be more beneficial in pain relief and knee joint function and quality of life improvement.However, the study had several limitations. First, the burials in the included studies may not be uniform, the method quality is poor, and confounding factors may be introduced. Second, the sample of our study was relatively small. All above limitations will be perfected in near future.In conclusion, warm needle moxibustion plus functional exercise can effectively improve the clinical symptoms of KOA patients, and improve their knee joint function and inflammatory response, which is worthy of clinical reference.


Idiopathic Scoliosis (IS) is the most common spinal deformity in adolescents, accounting for 80% of all spinal deformities. However, the etiology remains uncertain in most cases, being identified as Adolescent Idiopathic Scoliosis (AIS). IS treatments range from observation and sport to bracing or surgery. Several risk factors including sex and familiarity, have been linked with IS. Although there are still many uncertainties regarding the cause of this pathology, several studies report a greater incidence of the defect in families in which at least one other first degree relative is affected. This study systematically reviews the available literature to identify the most significant genes or variants related to the development and onset of IS.The research question was formulated using a PIOS approach on the following databases: Medline, Embase, Cinahl, Scopus, Web of Science and Google Scholar. The search was performed from July to August 2021, and articles from the inception of the database to August 2021 were searched.24 of the 919 initially identified studies were included in the present review. The 24 included studies observed a total of 16,316 cases and 81,567 controls. All the considered studies stated either the affected gene and/or specific SNPs. CHD7, SH2B1, ESR, CALM1, LBX1, MATN1, CHL1, FBN1 and FBN2 genes were associated with IS development.Although association can be found in some candidate genes the field of research regarding genetic association with the onset of IS still requires more information. Idiopathic Scoliosis (IS) is the most common spinal deformity in adolescents, accounting for 80% of all spinal deformities. However, the etiology remains uncertain in most cases, being identified as Adolescent Idiopathic Scoliosis (AIS) , 2. DiagSeveral risk factors such as sex and familiarity, have been linked with IS . MoreoveIS management is strictly related to the time of presentation and the value of the Cobb angle. The study by Weinstein et al. indicated bracing as an effective AIS treatment option in the case of non-surgical scoliosis (< 45° of Cobb angle). Another study by Hans-Rudolf Weiss reported that patients not treated for IS in the early stages of the disease  tended to have worse outcomes compared to ones treated early .Therefore, an early diagnosis and treatment could reduce the risks of intervention; furthermore, these improvements could lead to a decrease in the overall rate of complications in case of surgery.Genetic tests could diagnose IS before the beginning of characteristic symptoms, allowing early diagnosis and treatment. To our knowledge, however, few studies investigated specific genes related to IS onset. In the light of these considerations, the importance of refining strategies to predict and prevent the disease is evident and may be crucial to diagnosis and treatment.This study systematically reviews the available literature to identify the most significant genes or variants related to the development and onset of IS.The research question was formulated using a PIOS-approach: Patient (P); Intervention (I); Outcome (O) and Study Design (S). This systematic review aims to study the association (O) between patients that have developed IS (P) and specific genes, identified through genetic screening. Literature in which patients affected with IS were genetically tested (I) for mutations in genes of interest was reviewed. The following study designs were included (S): Randomized Controlled Trials (RCT) and Non-Randomized (NRCT) as Prospective (PS), Retrospective (RS), Case series (CS), Case–Control (CC), and Cohort (CS) studies.Only articles published in English were screened. Peer-reviewed articles of each level of evidence according to Oxford classification were considered. Only studies reported on affected genes in the onset of IS in patients were included.Technical notes, letters to editors, instructional courses or studies that did not include genetic testing of patients were excluded. Studies with a sample size smaller than 10 patients were considered not eligible for the present study. Studies with missing or incomplete data were also excluded. The analysis did not include degenerative, syndromic, and neurological scoliosis.A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Medline, EMBASE, Scopus, CINAHL and CENTRAL bibliographic databases were searched using the following string: ((diagnosis) AND ((genetic) OR (genome))) AND ((scoliosis) AND ((((adolescent) OR (idiopathic)) OR (early-onset)) OR (late-onset))). Keywords were used both isolated and combined. Additional studies were searched among reference lists of selected papers and systematic reviews.The search was performed by two authors (A.G. and M.M.) from July to August 2021 and articles from the inception of the database to August 2021 were searched.Two independent reviewers performed data collection (A.G. and M.M.), and differences were reconciled by mutual agreement. Any disagreement was resolved upon consultation of a third reviewer (S.D.S.). Firstly, title and abstract screening were performed, and then selected texts were reviewed in full text. The PRISMA flowchart, seen in Fig. General study characteristics extracted included: primary author, year of publication, country, type of study, level of evidence, sample size (cases and controls), affected gene, statistical association , diagnostic method, type of scoliosis (early or late-onset).The non-randomized control studies included in this review were assessed for the possibility of bias using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool by Cochrane. Cochrane's Risk of Bias 2 (RoB 2) tool was used to test for bias in randomized control studies. The scoring was performed by the authors A.G. and M.M. independently, and any disagreement was resolved by a third author S.D.S.The search resulted in 919 records identified, which went down to 917 after duplicate removal. Of the 917 records, 850 were excluded during title/abstract screening, leaving 67 articles for the full-text assessment. After the full-text assessment, 43 articles were not considered eligible for the study: some did not provide relevant information for the present review (n = 36) or provided insufficient data on the genes of interest (n = 2); one study was excluded because it included less than 10 participants and one article was not available in English. Thus, 24 studies were included for qualitative synthesis. Due to different identified genes in the collected data, a meta-analysis could not be performed.The 24 included studies observed a total of 16,316 cases and 81,567 controls. The high number of controls compared to cases is mostly accounted by Kou et al., who utilized three large genome wide association studies (GWAS) that included 73,884 controls compared to 5,327 cases.All the considered studies stated either the affected gene and/or specific single nucleotide polymorphisms (SNPs). Of the 23 studies 15 stated SNPs of the affected gene, 15–26, In regards to statistical data extracted, 11 studies included only the p-value–26, 28, Of the selected studies, the following levels of evidence and study designs were included: 10 level III case–control studies, 29, 30,All data discussed in the following section are reported in Table Alden et al.  evaluateFour of the included studies reported on CNV 16p11.2, Buchan et al. reported on various deletions and duplications; however, the proximal duplication 1q21.1 was the only one that showed a significant correlation to the onset of IS given its p-value of 0.0057 .Sadler et al. focused on gene SH2B1 with a 16p11.2 distal deletion and duplication , which sIn two other studies, Takeda et al. and Zhao et al. identified a 16p11.2 deletion , 17, 29 Borysiak et al. focused on three SNPs of the CHD7 gene. However, only rs101786 demonstrates a statistical association . These vKou et al. identified a specific SNP, of gene TBX6 rs1978060, with a statistically significant association between gene modification and IS onset .Estrogen Receptor Genes (ESRs) may be related to IS, specifically ESR1 and ESR2. In the three tested SNPs, Wang et al. reported a significant association for the missense variant in ESR1 and another missense variant in ESR2 , 28. ZhaSNP rs12885713.Another associated SNP is rs12885713 of the CALM1 gene, which Zhao et al. found a p-value of 0.034 .The LBX1 gene was identified in three included studies , 18, 20.While two studies both tested for the MATN1 gene, one for the 1p35 marker and the other for rs1149048, both reported no statistically significant association , 27.Moon et al. and Sharma et al. identified rs10510181, an SNP of the CHL1 gene; however, the two studies showed a discrepancy in p-value , 19. WhiFBN1 and FBN2.Buchan et al. gave p-value and odds ratio for FBN1 only, FBN2 only, FBN1 or FBN2: the p-value and OR were 0.0041 and 4.2, 0.0307 and 3.0, and 0.00054 and 3.5 respectively . These vUpon assessment using the ROBINS-I tool, the risk of bias for 11 of the studies was considered “low”, while 13 were found to have a “moderate risk of bias”. “Bias due to missing data” was the most common bias domain, followed by “bias due to selection of participants”. Most of the studies were similar in design and did not precisely describe the enrollment criteria of the participants Fig. .Fig. 2RONo Randomized Clinical Trials were not considered eligible; therefore, the RoB-2 tool was not used.Idiopathic Scoliosis is a multifactorial condition, and the present study focuses on exploring whether specific genetic mutations or polymorphisms could influence its onset , 33. UndThe CALM1 gene, along with CALM2 and CALM3, are genes that code for calmodulin, a calcium receptor protein involved in various cellular processes, including cell differentiation, cell proliferation, and cytoskeletal architecture and function, and metabolic homeostasis . This geThe studies by Buchan  and SadlFurthermore, data seems to support the idea that distal regions may exert regulatory effects on proximal regions of the CNV, including the TBX6 gene . This isKotwicki, Wang, and Wu et al. looked at estrogen receptors genes, but only the latter two found significant statistical association , 28, 30.15,16. LBX1 mutations have been linked to disruption of paraspinal development, which is regulated by the WNT/beta-catenin pathways [Three studies focused on the LBX1 gene , 18, 20,pathways . This mapathways . One spepathways . Microdupathways . Paraspipathways .Moon and Sharma identified rs10510181, an SNP of the CHL1 gene , 19. WhiThe LBX1 gene, beyond playing a role in embryological muscle development also specifies distinct neuronal subtypes in the spinal cord . LBX1 exHowever, both LBX1 and CHL1 influence the CNS and have both been statistically associated with IS onset.Data on genetic correlations with IS onset would benefit from some standardizing measures, including more consistent reporting of odds ratio and p-value as statistical measures, a standardized measure for reporting allele frequency, clearer inclusion and exclusion criteria for participants, and more participant data, including sex, age of IS onset, and ethnicity. These measures could improve the quality of preliminary data and allow for a more in-depth and accurate exploration of the genetic correlations with IS onset and facilitate comparison across different studies.The present review has some limitations. The study did not collect data from randomized control trials and included some low-quality studies.Secondly, the meta-analysis of results could not be performed due to the heterogeneity of the collected data. Only English-language articles were included, limiting the number of eligible articles. Most of the included studies did not distinguish between early-onset and late-onset scoliosis. This is a limitation because the information on the age of onset may have been relevant in understanding the function of the identified genes, or possibly allowed for discrimination between genes identified in early and late-onset.Another important point to mention is that due to the complexity of this topic contradicting data was sometimes found when searching for genetic correlations to the onset of IS likely due to its complex and multifactorial nature. The discrepancy between Moon et al. and Sharma et al. results regarding the same gene serves as an example.Furthermore, the present study does not consider the ethnicity of patients and consequentially the possible genetic differences between ethnic groups in relation to the onset of IS. Although more literature on the subject is required studies have reported differences in the prevalence of IS across various races , 45. ForSeveral studies show an association between the development of scoliosis and specific genes, SNPs, CNVs and markers. Therefore, identifying genes directly linked to the onset of scoliosis would represent a turning point in the diagnosis and treatment of this condition. However, it is not possible to draw a conclusion, due to the lack of high-quality evidence. For this reason, more numerous and higher-quality studies are needed.


Lung cancer screening (LCS) programs through low-dose Computed Tomography (LDCT) are being implemented in several countries worldwide. Radiation exposure of healthy individuals due to prolonged CT screening rounds and, eventually, the additional examinations required in case of suspicious findings may represent a concern, thus eventually reducing the participation in an LCS program. Therefore, the present review aims to assess the potential radiation risk from LDCT in this setting, providing estimates of cumulative dose and radiation-related risk in LCS in order to improve awareness for an informed and complete attendance to the program. After summarizing the results of the international trials on LCS to introduce the benefits coming from the implementation of a dedicated program, the screening-related and participant-related factors determining the radiation risk will be introduced and their burden assessed. Finally, future directions for a personalized screening program as well as technical improvements to reduce the delivered dose will be presented. Lung cancer (LC) is the most common cancer in Europe and ranges second in the USA, accounting for nearly 2.2 million new cases per year and the leading cause of cancer death, with up to 1.8 million deaths in 2020 . ConversThe effectiveness of LC screening (LCS) has been explored by several randomized trials ,11,12,13Suitability of a screening program depends on the selection of a target risk population that would benefit from screening, the accuracy of the screening test, its frequency and duration, as well as the economic burden and adverse effects . RadiatiSeveral studies reported a lack of knowledge on radiation risk from medical imaging among both physician and general population, this frequently leading to a biased understanding of the benefit-to-risk balance of radiological examinations ,28. TherWhile the secondary effects of high radiation doses are well known, those related to low-dose exposure by medical imaging are still debated. Based on epidemiological evidence from atomic bomb survivors, the National Academy of Sciences Biologic Effects of Ionizing Radiation (BEIR) VII report advanced a linear no-threshold (LNT) model to estimate the lifetime radiation-related risk of cancer . The LNTHence, in LCS, ethical concerns do not only arise from exposing healthy individuals to radiation by cumulative radiation exposure from iterative prolonged screening rounds, but also from the additional radiological investigations required for the work-up of lesions detected by LDCT. Such further investigations may include follow-up LDCT, Positron Emission Tomography/Computed Tomography (PET/CT), fluoroscopy during bronchoscopic procedures, or CT-guided biopsy.Several factors should be considered to estimate the risk related to radiation exposure in LCS, both screening-related  and participant-related .As a rule, CT protocols are established to ensure diagnostic quality images while keeping a low radiation exposure according to the “as low as reasonably achievable” (ALARA) principle. For LCS, LDCT is recommended to reduce the effective dose (ED). ED  is a derived value that estimates dose exposure and the related biological risk. For CT examination, the ED is calculated by multiplying the dose-length product , which is the product of the volume computed tomography dose index  by the scan length , using a specific conversion factor “k” of 0.0146 mSv/mGy x cm, according to IRCP103 .In LCS trials, the ED ranges from 0.2 mSv to 2.36 mSv ,38,39,40These single screening values that are lower than a regular chest CT (average of 3.8 mSv) are reassuring when considering individual average annual background dose of approximately 3–5 mSv ,45. MoreLCS over a prolonged period can enhance the screening benefit, leading up to a 58 and 39% reduction in LC mortality at 6 and 10 years, respectively . MoreoveAlthough cumulative dose may be reduced by biannual screening protocols, several societies recommend annual screening rounds ,52,53,54In contrast to the results from the initial screening rounds in the NELSON trial, the fourth round, performed 2.5 years after the third one, detected a significant number of interval LCs at an advanced stage, indicating that annual and biannual screenings are effective in early LC diagnosis, but increasing this to a 2.5-year interval may miss faster-growing lung cancers .In conclusion, shifting to a biannual screening would save many LDCT rounds and reduce both cumulative dose exposure and costs. Consequently, future research should focus on personalized interval screening algorithms to identify participants that benefit from annual and biannual screening ,58.The starting age differed among the trials, with 55-year-old in the NLST and ITALUNG trials versus 50-year-old in NELSON, DLCST, MILD and UKLS trials ,8,10,11.−4 in a woman starting at 50 years compared to 5.1 × 10−4 at 55 years [The radiation-related risk depends on the age at start of screening. While for most tissues and organs radiation sensitivity is greatest at a younger age, lungs are more sensitive when exposed at an older age, with a peak around 50–55 years. The radiation-related LC risk hypothetically decreases from 1.8 to 0.8% by deferring the initiation of annual screening from 50 to 60 years . The lif55 years , and the55 years .−4 at age 50 to 7.2 × 10−4 at age 55 [There are actually gender discrepancies in both benefit and radiation risk in LDCT. Several studies demonstrated that LCS is more effective in women than in men since women more frequently develop slower growing adenocarcinomas ,12,60,61t age 55 . The estt age 55 . OverallSmokers and former smokers are the target risk population for LCS. Carcinogenesis is increased in lungs exposed to tobacco and may synergistically augment the risk of developing cancer from radiation ,64. DosiSince the delivered ED depends on CT technology, facility protocol settings and patient’s body weight, guidelines setting the dose levels for LDCT in LCS have been published. In 2014, the American College of Radiology (ACR) recommended an upper limit for CTDIvol of 3 mGy for a standard-size patient with ≤1 mm thick images by using at least a 32 rows CT ,66. At tThe technical parameters recommended by the ESTI allow reduced radiation exposure when compared to those reported for most clinical trials; hence, the ED estimates for LCS should be lower than those reported to date.However, the accomplishment of these dose values is not straightforward. A prospective analysis of data from 12,529 participants who underwent LCS in 72 institutions by Demb et al., observed that CTDIvol and ED exceeded the ACR benchmarks in up to 18 and 50% of the participants, respectively . Higher The main goal of LCS implementation is to identify the best strategy to obtain a cost-effective program.In the USA, the implementation of LCS has encountered several issues, showing that a balance between invested effort and identification of individuals at risk, adherence to program and an acceptable benefit-harm-cost ratio is not as simple. Optimal participant selection, choice of screening intervals, and duration of program may reduce the potential issue and harms, such as participant dismissal, high costs, false positive results and excessive radiation exposure. The eligibility criteria for LCS in the USA rely on USPSTF2013 recommendations . HoweverRecent developments in software and hardware technology have enabled low-noise images while maintaining diagnostic quality images, that allowing further dose reduction . In partInteresting results come by deep learning iterative reconstruction (DLIR), an artificial intelligence method for CT image reconstruction that reduces background image noise, allowing image quality improvement and, consequently, a dose reduction of about 20% . In a prA new CT technology using photon-counting detectors (PCD) is under evaluation . PDCT-CTFinally, the value of magnetic resonance imaging (MRI) in nodule detection and volume assessment should also be explored, especially with low-field equipment at 0.55 T ,80. A piIn conclusion, currently available data from LCS trials and simulation studies are reassuring in terms of radiation burden from LDCT. Nevertheless, attention must be paid to the accurate selection of eligible subjects who are at the highest risk and the optimal CT protocols to minimize radiation-induced cancer risk during LCS rounds and additional investigations. Personalized screening algorithms and risk stratification, taking into account gender, age, interval time and duration are desirable to reduce unnecessary radiation exposure. A dedicated radiologist and medical physicist should optimize the LDCT protocol to comply with international guidelines and ensure an optimal image quality/radiation dose balance. Future technological advances that will improve image quality will probably allow further reduction on delivered dose in this setting.


Periodontitis and increased missing teeth were associated with an increased risk of RA. Maintaining good oral hygiene through frequent tooth brushing and regular dental scaling may reduce the risk of RA occurrence.Periodontitis and rheumatoid arthritis (RA) are inflammatory diseases that share many similarities. We aimed to investigate the associations of periodontitis and oral hygiene status and behaviors with RA in a nationwide general population cohort. Participants from the National Health Screening cohort database of Korea who underwent oral health screening by dentists between 2003 and 2004 were included. The occurrence of RA was analyzed according to the presence of periodontitis, oral health examination findings, and behaviors. Overall, 2,239,586 participants were included. During a median of 16.7 years, RA occurred in 27,029 (1.2%) participants. The risk for incident RA was higher when participants had periodontitis (hazard ratio (HR) 1.2, 95% confidence interval (CI), 1.08−1.24) and an increased number of missing teeth . In contrast, better oral hygiene behaviors, such as a higher frequency of daily tooth brushing (HR 0.76, 95% CI 0.73–0.79,  Periodontal diseases are common inflammatory diseases affecting nearly 30% of the adult population worldwide . PeriodoRheumatoid arthritis (RA), which has a prevalence of 0.5% to 2% worldwide, is a chronic inflammatory disease characterized by synovial inflammation that results in joint damage . RA is aPorphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, are suggested to play a crucial role in the link between periodontitis and RA [Periodontitis and RA share several genetic and environmental risk factors. Genetic risk factors, such as shared epitopes within the β-chain of human leukocyte antigen (HLA) and tyrosine phosphatase PTPN22), are involved in both diseases ,20. Smok, are invs and RA .Several epidemiologic studies have suggested a bidirectional relationship between periodontitis and RA. In US population data, patients with RA showed a 1.8 times increased risk of periodontitis . A histoThis study aimed to investigate the association of oral health examination estimates with the occurrence of RA with a null hypothesis of no association between oral health status or related behaviors and risk of RA in a nationwide population-based cohort database in a longitudinal setting. This study used the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort database of Korea. The NHIS, controlled and supported by the Korean government, is the sole insurance provider in Korea and is administered to almost 97% of Koreans. The remaining 3% of the population is supported by the Medical Aid program administered by the NHIS ,27,28. Pn = 167,106) for whom data on at least one variable of need, including oral health examinations and laboratory findings, were missing. Next, participants (n = 9271) with a previous history of RA from 2002 (including a one-year washout period) to before the oral health examination were excluded. Finally, 2,239,586 participants were analyzed in this study  ,30,31. Tis study .The index date was defined as the date of the oral health examination. The following baseline characteristics were identified on the index date: age, sex, household income, and body mass index. Information on smoking habits, alcohol consumption (frequency per week), and physical exercise (frequency per week) was collected using questionnaires. Smoking status was categorized as none, former, and/or current smoker. Periodontitis was defined as more than one claim including the diagnostics codes for periodontitis -10 codes: K052-K054) with at least one claim for one of the following procedure codes: U2232, U2240, U2233, U2221, U1010, U2211, U4454, U2222, U0010, U1051, U1052, U4455, U1060, U2231, M0111, and U4660 or a positive result on the oral health examination for a periodontal pocket detected by a dentist. Dentists also detected tooth loss during oral health examinations. The number of missing teeth was classified into four groups regardless of cause, such as periodontal disease or other dental reasons: 0, 1–7, 8–14, and over 15. Oral hygiene behavior was classified by the frequency of tooth brushing per day  and by whether the participant received dental scaling at least once in the last year ,13,14.The outcome of our study was the occurrence of RA based on two or more claims of the ICD-10 diagnostic code M05 with the copayment beneficiaries’ program (V223) with the prescription of any disease-modifying antirheumatic drug . This RAt-test for continuous variables. Continuous variables are presented as the mean ± standard deviation, and categorical variables are presented as numbers (percentages). Kaplan–Meier survival curves with the log-rank test were used to evaluate the association of oral health status and oral hygiene behaviors with incident RA risk. The number of RA cases was divided by the sum of person-years to estimate the RA incidence. Cox’s proportional hazard regression was used to determine the association of oral health status and oral hygiene behaviors with the occurrence of RA, and hazard ratios (HRs) and 95% confidence intervals (CIs) were determined. A multivariable regression model adjusted for age, sex, household income, body mass index, smoking status, alcohol consumption, regular physical activity, and comorbidities  was constructed. The number of lost teeth was divided into terciles and adjusted with no tooth loss as a reference. In consideration of the multicollinearity between oral hygiene and health behaviors, multivariable analysis was performed for each estimate regarding oral hygiene and oral health behaviors. Subgroup analyses for the association of the presence of periodontitis with the occurrence of RA were performed according to age, sex, and covariates. Regarding sensitivity analysis, a multivariable analysis was performed after excluding participants with RA within one year from the index date to minimize the possibility of reverse causality . The assumption of the proportionality of hazards was tested using Shoenfeld’s residuals. No departure from the proportional hazards assumption was detected. All statistical analyses were performed using Statistical Analysis System software . All values with p-values < 0.05 were considered statistically significant.We used the chi-square test for categorical variables to compare the baseline characteristics and the independent Among a total of 2,239,586 participants, the average age of the included participants was 42.3 ± 12.8 years, and 66.4% were male. A total of 13,926 (0.6%) participants had more than 15 missing teeth, 923,237 (41.2%) participants brushed their teeth more than three times a day, and 512,683 (22.9%) participants had dental scaling within the previous year. The baseline participant characteristics and a comparative analysis according to the presence of periodontitis are shown in p < 0.001) and an increased number of missing teeth (p < 0.001). Moreover, better oral hygiene behaviors including a higher frequency of daily tooth brushing and a history of dental scaling within the previous year were also associated with a lower occurrence of RA (p < 0.001)  years, RA occurred in 27,029 (1.2%) participants. < 0.001) .p <0.0001). An increased number of missing teeth was associated with an increased risk of RA; the adjusted HR (in reference to subjects with no missing teeth) was 1.52  for participants with more than 15 missing teeth. Furthermore, an increased frequency of tooth brushing was negatively correlated with the occurrence of RA. In reference to participants who brushed their teeth less than once a day, subjects who brushed their teeth more than three times a day  had a decreased risk of RA. Moreover, participants who received dental scaling within one year showed a significantly lower risk of occurrence of RA than those who did not   . In the = 0.013) . In the sensitivity analysis with a landmark analysis, the associations of periodontitis, number of missing teeth, frequency of tooth brushing, and dental scaling with the occurrence of RA were consistently noted even though the outcome (occurrence of RA) was redefined as RA after one year from the index date . This study revealed that periodontitis and increased tooth loss were associated with an increased risk of seropositive RA and that maintaining better oral hygiene through frequent tooth brushing and dental scaling was associated with a decreased risk of RA. Several clinical, epidemiological, and serologic studies have shown a bidirectional association between periodontitis and RA ,18,34. PAn increased number of missing teeth was a risk factor for RA occurrence in our study, which is similar to the findings of previous reports. Pablo et al. showed that the prevalence of tooth loss was higher in patients with RA, and the association with complete tooth loss was robust in patients with seropositive RA . This asP. gingivalis, is a unique anaerobe that can express PAD and produce citrullinated peptides, which trigger ACPAs. With their various virulence factors, local inflammation of the gingival mucosa and synovial membrane is exacerbated by proinflammatory host immune responses and by inhibition of the host’s protective mechanism due to citrullination and protease degradation [P. gingivalis induced periodontitis and ACPA-associated RA in an experiment with rats [P. gingivalis, other periodontal pathogens such as Treponema denticola and A. actinomycetemcomitans have also been shown to be associated with RA and are being studied [Although our study did not demonstrate the mechanism of the link between periodontitis or tooth loss and the development of RA, some basic research support this association. Some periodontal bacteria that are crucial in the development of periodontitis have been suggested to induce autoimmunity in RA. The detection of antibodies against periodontal pathogens and DNA from periodontal bacteria in serum and synovial fluid of patients with RA supports this idea ,42. Bactradation . As expeith rats . In partith rats ,45,46, o studied . Althoug studied ,48, it mPoor oral hygiene is a critical factor associated with periodontitis and tooth loss; thus, maintaining good oral hygiene through tooth brushing and frequent dental visits is associated with a reduced risk of periodontitis . RecentlMoreover, this association between oral care behaviors and disease was reported in patients with RA ,54. KharThere are some limitations in our study. Firstly, the severity of periodontitis, such as the detailed attachment loss, could not be investigated due to the nature of the data. Secondly, our study design cannot suggest a causal relationship as a retrospective observational study. Although the severity of periodontitis was not described in every subject, our data based on the results of an oral health examination performed by a dentist could minimize the error. Furthermore, this study has strengths in that we used large-scale nationally representative data that have been tracked for a long time to elucidate the association of oral health and oral behaviors with the occurrence of RA. Our nationwide results provide unique evidence supporting the benefits of improving oral hygiene or behavior for RA prevention.The presence of periodontitis and an increased number of missing teeth may be risk factors for the occurrence of RA. Better oral hygiene care including tooth brushing and dental scaling might be associated with a decreased risk of RA. Further studies supporting the causative relationship between oral hygiene and RA are needed. Understanding the underlying mechanisms of the inter-relationship between oral hygiene and RA might be a cornerstone in finding novel predictive markers of disease initiation in individuals at risk of RA.


Data of the Autism Diagnostic Interview–Revised were available for 428 participants . By means of binominal logistic regressions and an ensemble feature selection, we identified a subset of items that best differentiated between autism spectrum disorder and mood and anxiety disorder. Overall, the results indicate that a combination of communicational deficits and unusual and/or inappropriate social overtures differentiates autism spectrum disorder and mood and anxiety disorder. Aspects of social cognition are also relevant. Limitations of the current study and implications for research and practice are discussed.Autism spectrum disorder shares many symptoms with other mental health disorders, and comorbid disorders such as mood and anxiety disorders are common, making the diagnostic process challenging. We aimed to explore the diagnostic accuracy of two standard autism spectrum disorder diagnostic instruments and to identify those behavioral items that best differentiate between autism spectrum disorder and mood and anxiety disorder in a naturalistic sample of patients utilizing autism spectrum disorder specialist services. The study included data of 847 participants (5–65 years of age, Symptoms of mood and anxiety disorders overlap with symptoms of autism spectrum disorder, making the diagnostic process challenging. This study found that a combination of communicational deficits and unusual and/or inappropriate social overtures facilitates differentiation between autism spectrum disorder and mood and anxiety disorders. Furthermore, the results confirm the essential need of a behavioral observation with the Autism Diagnostic Observation Schedule in combination with a full Autism Diagnostic Interview–Revised to support diagnostic decisions. Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a worldwide prevalence of just less than 1% . ComorbiBesides high rates of comorbidities, the differentiation of ASD versus mood or anxiety disorder (MAD) can be difﬁcult. Clinical observations as well as research results have revealed symptom overlap between ASD and MAD, meaning that symptoms occur in ASD as well as in MAD. Respective symptoms are preoccupations, repetitive behaviors (e.g. obsessions and compulsions), and speech irregularities. Furthermore, individuals with ASD and those with MAD show deficits in emotion recognition , avoidanFurthermore, MAD and ASD are difficult to distinguish because of overlapping predictors in early life , such asIn a clinical context, the differentiation between ASD and MAD has particular implications for treatment planning. The most frequently evaluated psychological treatment for anxiety disorders is cognitive behavior therapy (CBT), which involves the application of exposure techniques to enable the individual to endure feared situations accompanied by cognitive restructuring procedures. Misclassification of anxiety disorder as ASD could increase the risk that this individual would not get these effectful interventions on time. In addition, there is evidence that individuals with anxiety disorders with some ASD traits (but not fulfilling a diagnosis of ASD) benefit more from family-oriented CBT compared with individual CBT , whereasIn summary, there are a high amount of symptom overlap and high rates of comorbidities between ASD and MAD, leading to a challenging diagnostic process that requires diagnostic instruments with sufficient specificity to plan adequate treatment regimens. To understand the differences between diagnostic categories, disorders are usually compared in individuals without comorbidity to describe single diagnoses among individuals with overlapping symptoms e.g. , 2016. WIn this study, we thus examined scores of the Autism Diagnostic Observation Schedule ADOS;  and the Data from the current study were extracted from an established research database of the ASD-Net, a state-funded German research network , which wInternational Statistical Classification of Diseases and Related Health Problems, 10th Revision , neuropsychological testing, reports from other institutions, school reports, home videos, ADOS, ADI-R, differential diagnostic examination with established structured questionnaires and structural clinical interviews frequently used in German-speaking countries;  ICD-10; . Differen = 586 with ASD, n = 261 with mood, anxiety, or emotional disorders), all evaluated with the ADOS in the context of the diagnostic process. The sample was separated for the identification of the most discriminative behavioral items insofar as individuals were administered different measures (i.e. ADOS modules) depending on age and language ability. The subgroups are henceforth labeled Module 3  and Module 4 . A total of 560 participants were tested with Module 3  = 4; n = 172 with MAD, 18.6% female, 5–17 years of age, median age = 10.0, IQR = 4), whereas 287 individuals were tested with Module 4 . Complete ADI-R data were available for 428 participants .The study included data of 847 participants , 2  to 3 (profound severity), with additional codes of 7 and 8 for abnormal behavior or behavior not exhibited during the observation, and a code of 9 for missing values (i.e. answers omitted or left blank). The behavioral items were grouped into two domains: social affect (SA) and restricted and repetitive behavior (RRB). The ADOS diagnostic algorithms yield classifications of autism and autism spectrum versus non-ASD.The German Versions of the ADOS , a standardized, semi-structured clinical interview for caregivers of individuals suspected of having ASD. Responses are scored by trained administrators based on the caregiver’s description of the child’s behavior. The ADI-R yields three domain scores based on behavior , which are calculated by summing items within the areas of qualitative abnormalities in reciprocal social interaction , qualitative abnormalities in communication (communication), and restricted, repetitive, and stereotyped patterns of behavior (RRB). Totals from domains can be compared with algorithm cutoffs that yield classifications of autism or nonautism.For data preparation, ADOS and ADI-R codes of 7 and 8 were recoded to 0, and domain scores were calculated as suggested in the ADOS and ADI-R manuals after codes of 3 were recoded to 2. For Module 3, the ADOS-2 algorithm was used to calculate scores. For Module 4, the revised algorithm of ADOS-2  and the To explore the diagnostic accuracy of standard ASD diagnostic instruments (Aim 1), ADOS algorithm cutoff scores, domain scores for SA, RRB, and the total calibrated severity scores (CSS) were calculated for the full sample. Based on the algorithm cutoffs, percentages of MAD and ASD cases meeting diagnostic thresholds of the ADOS and ADI-R were computed. Group differences on domain levels of ADOS  and ADI-R  were tested by analyses of variance.To identify specific profiles of ASD symptoms on domain and item level in individuals with MAD compared with individuals with ASD (Aim 2), we first identified items that discriminated best between ASD and MAD by a methodology for discrimination purposes .To determine the most important items suitable for accurate classification of ASD versus MAD cases (Aim 3) in the full sample, we performed an ensemble feature selection  and a test of exclusion based on Wald statistics, following a chi-square distribution . Thus, items were added to the regression model, if they lay under the cutoff for exclusion and if a significant improvement in the model is achieved.Subsequently, in a separate analysis, binominal logistic regressions were computed on two subsamples as the samples of ADOS Modules 3 and 4 differ widely concerning age see . RegressComplete IQ data were available for 690 participants (81.5% of the entire sample), whereas IQ-level data  were available for 753 participants (88.9% of the entire sample). Preliminary analyses on significant group differences on age, IQ, and IQ level are reported in n = 29) met the autism spectrum cutoff, whereas 7.0% (n = 12) met the autism cutoff. In Module 4, 16.9% (n = 15) met the autism spectrum cutoff and 9.0% (n = 8) met the autism cutoff of the revised algorithm. For the ADOS-G algorithm of Module 4, 19.1% (n = 17) met the autism spectrum cutoff, whereas 7.9% (n = 7) met the autism cutoff.In Module 3, 16.9% of the MAD sample (n = 45), an anxiety disorder subgroup , and an emotional disorder with onset specific to childhood group . About 25.0% of the anxiety disorder group, 17.8% of the mood disorder group, and 15.2% of the emotional disorder group met ADOS spectrum cutoffs. In contrast, 88.9% of the ASD sample in Module 3 (ADOS-2) and 80.3% of Module 4  met autism spectrum cutoffs. Investigations of the ADI-R showed that 34.4% of the MAD sample met algorithm criteria for the reciprocal social interaction domain, 18% for the communication, and 26.2% for the RRB domain. In total, 49.2% of MAD cases met at least one out of three ADI-R thresholds, 19.6% fulfilled two, and 9.8% all three thresholds. However, only one of the six participants who fulfilled all three thresholds of the ADI-R also met the ADOS autism spectrum algorithm cutoff.To explore whether there was a specific subgroup of the MAD sample that exceeded the thresholds, we divided the MAD sample into a mood disorder subgroup  = 503.82, p < 0.001, η2 = 0.47; CSS SA: F = 491.5, p < 0.001, η2 = 0.47; and CSS RRB: F = 202.7, p < 0.001, η2 = 0.27. For Module 4, CSS Overall: F = 157.3, p < 0.001, η2 = 0.36; CSS SA: F = 206.5, p < 0.001, η2 = 0.42; and CSS RRB: F = 37.8, p < 0.001, η2 = 0.12. As illustrated in F = 103.2, p < 0.001, η2 = 0.20; communication: F = 57.81, p < 0.001, η2 = 0.12; and RRB: F = 39.28, p < 0.001, η2 = 0.08.Algorithm scores for ADI domains were presented in Six items of Module 3 see  met critThe model based on ADOS items of Module 3, identified by logistic regression, explained 76.8% of the variance. In addition, the percentage of accuracy in classification (PAC) was high with PAC = 91.3% . Six items were included into the model indicating to be discriminative see , of whicFor Module 4, the logistic regression model explained 50.6% of the variance. The PAC was lower than for Module 3 with 83.6% . Five items were included into the model see . One iteLogistic regression was also calculated for ADI-R algorithm items, resulting in a model explaining 35.5% of the variance. Total PAC was 87.8% by better PAC for ASD (97.5%) than for MAD (29.5%). Five ADI-R items were identified to discriminate between ASD and MAD see .The results of the EFS  are presDue to high rates of comorbidities and a wide symptom overlap with other psychiatric conditions, the  diagnostic process of ASD in clinical settings can be challenging. This is particularly true for the assessment of verbally fluent children, adolescents, and adults with multiple social and behavioral problems. Thus, more finely tuned and precise information about the symptom overlap and differences between ASD and other mental disorders such as MAD is needed to create a better understanding for diagnostic purposes as well as tailoring individualized treatment strategies. We explored ASD symptoms in patients with MAD who were initially referred to ASD specialized clinics with suspicion of ASD and thus represent a well-balanced and most relevant clinical sample. By examining those behavioral aspects that best discriminate between ASD and MAD, this study contributes substantially to the understanding of differential diagnoses in ASD and highlights the need to be cautious in overestimating the diagnostic utility of the established instruments to support diagnostic decision-making in clinical samples with symptoms of mood, anxiety, and emotional disorders.Several patients of the MAD group showed ASD symptoms to an extent exceeding the diagnostic thresholds of the instruments. This indicates a high amount of symptom overlap between these two disorders. Given the fact that the examined participants were referred to specialized ASD clinics due to ASD concerns, this result is not surprising and consistent with previous studies showing that the disorders share a substantial number of symptoms . In our In our study, percentages exceeding ADI-R threshold were high for MAD participants, compared with those reported in a study by In line with The ADOS performed slightly better than the ADI-R, resulting in more items identified to adequately discriminate between the MAD and ASD groups. On the basis of a more clinical-methodological approach , our results indicate that the ASD group scored significantly higher on all domain scores of the ADOS and the ADI-R, despite high variance, outliers and low to medium effect sizes.The number of ADOS  items that met criteria for adequate distinction between groups was small. Furthermore, there is an outstanding qualitative difference in symptom overlap between ASD and MAD, as examined in our study, compared with results on ASD versus ADHD by Results of regression analyses indicate that, especially for Module 3, a satisfactory amount of variance could be explained by the identified model with high percentages of accuracy in classification. Besides already mentioned discriminating items , we found that the use of stereotyped words or phrases is a strong indicator for ASD. Abnormalities in insight and gestures also increase probability of ASD. Reduced reciprocal social communication and abnormalities in insight and empathy are indicators for ASD, whereas abnormalities in offering information increase the probability of MAD in adolescents and adults. These results indicate that a combination of communicational and social cognition aspects is relevant for the discrimination between ASD and MAD, while many other items overlap in ASD and MAD. Of course, the observation of anxiety-related symptoms—including initial wariness or self-consciousness as well as more obvious signs of worry, upset or concern—is a significant indicator for MAD and should thus receive close attention during administration of the ADOS. Our results indicate that retrospective information from caregivers alone, as collected by the ADI-R, is not appropriate for the discrimination of ASD and MAD.By using an EFS approach, a quantification of the importance of all single features of the ADOS in combination with the ADI-R could be obtained. A combination of eight items (five from the ADOS and three from the ADI-R) could be identified to increase both sensitivity and specificity. It seems that the combination of these instruments is essential to accurately classify ASD versus MAD.The gold standard in ASD diagnostic processes is the combination of a behavioral observation through the ADOS, which is conducted via one-on-one interaction and observation for a limited time period and, at a present time point, with an extensive determination of anamnestic data . AnamnesIn accordance with other studies , we founThis selected number of items that show significant discrimination between ASD and MAD could be—in addition to be considered within an ASD diagnostic evaluation—the foundation for the development of a specific screening instrument with training tools for clinicians to evaluate indications of ASD .One limitation of this work is that the substantial sample size still did not allow for differentiation between different mood and anxiety subcategories. Thus, more finely tuned information on even more subtle differences between the different symptomatology could not be derived and should be subject to future investigations. Our sample included individuals with MAD with suspicion of ASD, which is not representative for all individuals with MAD. In addition, as individuals with comorbid ASD and MAD were explicitly excluded from the analyses, results cannot be transferred to this subgroup. Therefore, future studies should investigate clear features that characterize this patient group of comorbid ASD and MAD. Furthermore, although the sample comprises an expectable number of female cases, separate analyses for female individuals, which would be desirable from both a clinical and a theoretical perspective, did not seem appropriate. In addition, there may be confounders that were not considered in our analyses like the child’s intellectual as well as adaptive functioning, comorbidities, and changes in anxiety across development. There is evidence that these factors affect the development and intensity of MAD symptomatology also in individuals with ASD . TherefoDiagnostic and Statistical Manual of Mental Disorders  or ICD-10 diagnostic criteria. Caution is required if the clinician observes symptoms of anxiety . A differential diagnostic examination with respect to any anxiety or mood disorder has to be undertaken to decide whether observed social impairment or repetitive, stereotyped behavior is explainable through the diagnosis of MAD or clearly meets diagnostic criteria for an additional ASD diagnosis.Our results suggest that—similar to There are several further clinical conclusions that result from our study. First, the differentiation of ASD and MAD is difﬁcult, and ADOS and ADI-R items are important to master the challenge. Second, when symptoms of MAD are evident in patients with marked deficits in the domain of social interaction, timely interventions have to address both symptoms. In some cases, the symptoms of ASD and MAD are overlapping to such an extent that it is necessary to start interventions targeting symptoms of MAD. CBT is an effective treatment not only for patients with MAD  but also


The total consistency of the AI immunophenotypic diagnosis and the manual results was 0.889 . The consistency and speedup of the AI-assisted workflow indicate its promising clinical application.We developed an artificial intelligence (AI) model that evaluates the feasibility of AI-assisted multiparameter flow cytometry (MFC) diagnosis of acute leukemia. Two hundred acute leukemia patients and 94 patients with cytopenia(s) or hematocytosis were selected to study the AI application in MFC diagnosis of acute leukemia. The kappa test analyzed the consistency of the diagnostic results and the immunophenotype of acute leukemia. Bland–Altman and Pearson analyses evaluated the consistency and correlation of the abnormal cell proportion between the AI and manual methods. The AI analysis time for each case  was significantly shorter than the average time for manual analysis . The total consistency of diagnostic results was 0.976 (kappa (κ) = 0.963). The Bland–Altman evaluation of the abnormal cell proportion between the AI analysis and manual analysis showed that the bias ± SD was 0.752 ± 6.646, and the 95% limit of agreement was from −12.775 to 13.779 ( Leukemia is a malignant clonal disease of hematopoietic stem cells. The diagnosis of leukemia is made by a combination of clinical findings, morphologic examination of peripheral blood (PB) and bone marrow (BM) specimens, and cytogenetic and molecular data, as well as immunophenotypic analysis by multiparameter flow cytometry (MFC) ,2,3. In As reported, AI has been used in the prognosis of breast cancer and gastric cancer, as well as the diagnosis of colorectal cancer and the differential diagnosis of malignant or benign masses in the breast ,12. MoreIn this study, we evaluated an AI-assisted methodology for the diagnosis of leukemia, including the diagnostic results, abnormal cell proportion, and cell phenotypic diagnosis, as well as compared the method’s diagnostic accuracy with that of conventional manual analysis. A clinic-orientated AI-assisted diagnosis workflow was validated to perform automatic data analysis with not only the final diagnostic results, but also human-understandable and editable intermediate steps.The study group consisted of 200 acute leukemia patients who were referred to the First Affiliated Hospital of Sun Yat-Sen University from March 2019 through June 2020. The diagnosis of acute leukemia was made according to the current WHO classification criteria by a combination of clinical findings, morphologic examination of PB and BM specimens, and cytogenetic and molecular data . Cases wBM aspirate samples were collected in EDTA anticoagulant and processed within 24 h of collection. After incubation with monoclonal antibodies for 20 min at room temperature, erythrocytes were lysed with ammonium chloride  at room temperature for 10 min using a standard lysing/washing technique. An eight-color FCM analysis was performed on a FACS Canto Plus flow cytometer , which was standardized daily using CS&T beads, and data were analyzed. The panel of antibodies used was CD45 , CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD13, CD14, CD15, CD16, CD19, CD20, CD22, CD33, CD34, CD38, CD56, CD64, CD117, HDL-DR, MPO, CD79a, and cCD3. Some cases of AML, such as AML M6, CD235a and CD71, as well as AML M7, CD41, CD42b, and CD61, were also included in the panel. The antibody panel is shown in Deepflow is an AI-assisted flow cytometry analysis software that was developed by DeepCyto LLC, WestLinn, OR, USA. DeepFlowVeriosn 1.0.1 was evaluated in this study on both leukemia and non-leukemic cases. The AI-assisted workflow consists of five major analysis phases: (1) data validation, (2) population classification, (3) immune-phenotype classification, (4) AI-assisted diagnosis, and (5) report generation. These five phases are discussed in detail in below.The data validation incorporates multiple machine learning models to extract nucleated single cells from the raw MFC data, such as flow time stability screening, doublets filtering, and debris removal, as shown in In the population classification phase, a multidimensional density–phenotype coupling (MDPC) algorithm specially developed for MFC data is applied on all of the nucleated cell data. The algorithm considers all of the channels’ distributions and phenotypes at the same time and automatically adjusts a cluster’s span according to the overall distribution. Two main criteria are used to differentiate the cell populations: the cell distribution density across all of the markers, and the marker expression phenotype on all of the markers . The pervasive expression levels of each channel are classified into five levels: bright, positive, partial, dim, and negative. A new cell population will be created whenever these two criteria are met. At the end of this phase, all of the nucleated cells are clustered into cell groups, each of which is given a unique population ID. Considering that acute leukemia usually reaches above 20% in terms of the abnormal cell percentage, the MDPC algorithm is optimized for large cell groups (5% and above).All of the cell clusters from the previous phase are classified in the population classification phase. In this phase, a random forest classifier with bootstrap aggregating is built for each tube. According to each tube’s specific antibody combinations, the AI models can not only characterize five common categories ) in each tube, but they can also distinguish some subcategories, such as T-cells and B-cells, and identify blasts’ lineages. In the AI-assisted diagnosis phase, a diagnosis AI model gathers all of the previously obtained information, affirms acute leukemia subtypes and negative cases, and raises diagnostic warnings. The AI model adopts a boosted random forest algorithm and takes the input of all of the categorized cell clusters, which are parameterized based on its ratio, category, and phenotypes. For the normal cell clusters, such as lymphocytes, monocytes, and granulocytes, the AI model examines and reports any unusual expression. The AI model also analyzes the abnormal cell clusters, combines clusters with similar expressions, computes the cell percentages, and diagnoses the acute leukemia’s subtype.The report generation is the last phase of the AI-assisted workflow. Along with the diagnosis, 2D scatterplots that reveal the intermediate results  are automatically integrated into a FCM diagnosis report in one PDF file, as shown in The consistency analysis of AI results and manual results was carried out by kappa analysis and Bland–Altman analysis. SPSS software was used for kappa analysis, and Graphpad Prism 5 was used for Bland–Altman analysis.p value of less than 0.05 was considered to be statistically significant.Statistical analysis was carried out by SPSS Statistics version 25 and Graphpad Prism 5. A two-tailed n = 23), postchemotherapy bone marrow suppression (n = 26), autoimmune cytopenia(s) (n = 16), chronic renal insufficiency (n = 9), iron deficiency anemia (n = 6), and drug-induced cytopenia(s) (n = 9). The mean age of the leukemia-positive group and non-leukemic group was 43.12 ± 11.05 and 39.59 ± 9.18 (years), respectively. The sex and age between the leukemia patients and non-leukemic-patients had no statistically significant difference (p > 0.05).The leukemia-positive group included 200 acute leukemia patients: 95 men and 105 women. The non-leukemic group included 44 men and 50 women. The non-leukemic group included five patients with aplastic anemia and 94 patients with cytopenia(s) or hematocytosis attributable to a variety of non-neoplastic conditions, including infection , which indicates that the abnormal cell proportion of AI and manual results had significant correlation. As shown in p = 0.1225).The abnormal cell proportions of the AI and manual results were 64.487 ± 23.36 and 62.973 ± 22.693, respectively. As shown in As shown in MFC plays a crucial role in the diagnosis of acute leukemia. In the past decade, many machine learning attempts have made been to solve the flow cytometry data analysis problem. Most machine learning applications in MFC data focus on the biomedical research field, but an AI solution for clinical flow cytometry application is still lacking for several reasons.First, the motivation of the research flow cytometry is to be innovative, which pushes the continuous trial of different panel designs with constant changes in reagents in a small batch of samples ,17. In cSecond, most published AI attempts in the flow cytometry field have been based on an end-to-end black-box approach, which lack the human understandable intermediate diagnosis results, and clinical practitioners have found them to be difficult to review and validate ,24. TherIn our study, we established an AI model to analyze the data of MFC, which can assist examiners in making a diagnosis of leukemia. Our results show that the AI model could quickly detect abnormal cell proportion and cell phenotype to obtain the diagnostic results. Comparably, the consistency of diagnostic results between AI analysis and manual analysis was high. Seven cases were manually diagnosed as leukemia . In contrast, AI only found abnormal blasts and raised a prompt for manual review. These cases were not easily diagnosable cases. All four AML cases were MPO negative and cross-expressed lymphoid antigens such as CD7 or/and CD56. Moreover, in the three ALL cases, the expression of the lymphoid-lineage-specific marker such as cCD3 or CD79a was dim, and myeloid antigens such as CD13 or/and CD33 were cross-expressed. Actually, the correct diagnosis of such cases is challenging for tyro. In this situation, AI did give abnormal-diagnosis hints, indicating that further manual review was needed. Of course, in the future, with a larger training set containing more atypical phenotypes, AI can be used to make a more definitive diagnosis, even for less common cases. Moreover, the detection of abnormal cell percentage and MFI results were also in close numerical range.The average time of the manual analysis of each sample FCM assay test was about 15 min by experienced examiners; the analysis speed of the AI model  was 10 times faster than that of traditional manual analysis. In addition, AI analysis significantly reduced the error of entry and calculation introduced by manual analysis.p < 0.04), which indicates a good correlation of the AI model and manual analysis.As shown in As shown in We investigated the potential for using the AI-assisted methodology to help pathologists identify abnormal cell populations faster and more objectively. This study focused on acute leukemia cases. More flow cytometry panels  will be included in future research to test the generalization ability of the AI methodology for flow cytometry. Further validation will be made by testing the AI methodology on the variant FCM panels from different laboratories. As flow cytometry is highly customized in panel design, AI can help standardize the hematology diagnosis in flow cytometry. The AI model established in this study is mainly based on clustering, classification, and dimension-reduction algorithms. In the future, we will try to use the method of a convolutional neural network  to more In summary, a clinic-orientated AI-assisted diagnosis workflow was validated to perform automatic data analysis with not only the final diagnostic results, but also human-understandable and editable intermediate steps. Specifically, the AI-assisted diagnostic system adopts customized machine learning algorithms for all of the clinical MFC analysis stages, and each step produces intermediate human-readable results that follow the same diagnosis logic in the manual analysis workflow. Therefore, a pathologist can easily understand and evaluate the AI-generated results. Moreover, the AI-assisted workflow supports interactive editing in each step, where the pathologist can decide to accept or adjust the results. This provides extra flexibility so that AI can adaptively learn each pathologist’s personal preferences in the gating and diagnosis process. AI-assisted automated MFC analysis is promising in leukemia diagnosis, and it is more rapid and effective. In addition, it can be integrated with other test findings, such as morphological, cytogenetic, and molecular abnormalities, to diagnose and stratify the prognosis of acute leukemia. Although its clinical application still needs to be further validated, this scalable system can be used as the basis for a clinical decision-making support system.


LRRC8B (Leucine Rich Repeat Containing 8 VRAC Subunit B) gene was selected to evaluate the association between its genetic variations and the body conformation traits in two native sheep breeds in China. Four body conformation traits, including withers height, body length, chest circumference, and body weight, were collected from 269 Chaka sheep. We also collected the body length, chest width, withers height, chest depth, chest circumference, cannon bone circumference, and height at hip cross of 149 Small-Tailed Han sheep. Two different genotypes, ID and DD, were detected in all sheep. Our data showed that the polymorphism of the LRRC8B gene was significantly associated with chest depth (p < 0.05) in Small-Tailed Han sheep, and it is greater in sheep with DD than those with ID. In conclusion, our data suggested that the LRRC8B gene could serve as a candidate gene for marker-assisted selection in Small-Tailed Han sheep.Marker-assisted selection is an important method for livestock breeding. In recent years, this technology has been gradually applied to livestock breeding to improve the body conformation traits. In this study, the  LRRC8 gene family was discovered in recent years, and it is composed of five subunits, namely LRRC8A, LRRC8B, LRRC8C, LRRC8D, and LRRC8E [LRRC8A is the most important subunit of the VRAC channel, and it co-expresses with one or more of the other subunits to constitute correct VRAC liveness [LRRC8A is essential for the formation of the VRAC channel. Notably, gene expression should remain in a certain level, and the overexpression of the LRRC8A gene may interfere with the normal activity and function of the VRAC channel [The d LRRC8E ,2. Specid LRRC8E ,4,5,6. Id LRRC8E ,11,12,13d LRRC8E  and is cliveness . Therefo channel ,16.LRRC8A and other LRRC8 proteins in the LRRC8 gene family can produce VRACs with different functional characteristics. Moreover, the difference in VRAC activity that the LRRC8A/B isomer causes may depend on the cell type and different physiological conditions [LRRC8A/D isomer is the main pathway through which cells are responsible for excreting GABA (γ-aminobutyric acid), taurine, and inositol [LRRC8A/E isomer is activated by intracellular oxidation, whereas the LRRC8A/C and LRRC8A/D isomers are restrained by oxidation [LRRC8A/C and LRRC8A/D isomers, the activity of the LRRC8A/E isomer is significantly inhibited by positive membrane potential [In addition, studies have shown that the co-expression of nditions . The LRRinositol ,18. The xidation . Compareotential .LRRC8B gene, a protein coding gene, is an important member of the LRRC8 gene family. Specifically, the LRRC8B protein, a subunit of the channel complex, takes part in regulating the substrate specificity of the channel and participates in intracellular Ca2+ homeostasis through an endoplasmic reticulum leakage channel [LRRC8B gene is closely related to the lung transplantation process and can be used as a new therapeutic target for lung transplantation complications [LRRC8B gene in livestock and poultry breeding.The  channel ,20. Furt channel ,22,23. I channel . In addiications . HoweverAfter years of continuous development and improvement, molecular marker breeding with InDel (Insertion and Deletion) technology has become one of the most important methods for livestock and poultry breeding . Recent In terms of the formation mechanism, CNV, InDel, and SNP have different emphases. The formation of CNV is mainly due to non-allelic homologous recombinationg (NAHR), non-homologous end joining (NHEJ), and fork stalling and template switching (FoSTeS). NAHR usually occurs during meiosis, when the copy number is changed due to the exchange of genome sequences. NHEJ is a DNA damage repair mechanism existing in the body, which can reconnect broken DNA and inevitably introduce copy number, resulting in mutation. FoSTeS is the result of DNA replication using the wrong replication template, which also causes mutations to occur. SNP is mainly the variation produced by adaptation to the environment. In the process of biological evolution, mutation is inevitable, and the most common mutation type is SNP. In order to survive, favorable variation is preserved. The generation of InDel is mainly related to the characteristics of genome and DNA replication errors. When the genome sequence is AT(A/C)(AC)GCC and TACCRC, the probability of insertion will be increased. However, sequences containing TATCGC and GCGG are not susceptible to insertion and deletion mutations. InDel is more likely to be produced in regions with high replication; for example, the occurrence frequency of euchromosomes is lower than that of sex chromosomes . In addiAs germplasm resources are dwindling, it is crucial to breed high-quality sheep. There are many types of sheep breeds in China, but most of them have poor performance and cannot satisfy people’s increased demand. Chaka sheep and Small-Tailed Han sheep are two good breeds in our country, widely distributed throughout the country. Chaka sheep, which live in Wulan County, Qinghai Province, are a famous hybrid breed of sheep used for local wool and meat with high meat quality but low yield . On the A total of 269 healthy Chaka sheep aged from 1 year old to adults were randomly selected from Chaka Town, Wulan County, and they had no blood relationship with each other. This included 83 male sheep, 101 female sheep, and 85 wether sheep for which experimental records were made. A total of 149 healthy Small-Tailed Han sheep with no blood relations were also randomly selected from Ruilin Technology Breeding Co., Ltd., Yongjing County, Gansu Province, China, including 85 male sheep and 64 female sheep for which experimental records were made. Notably, these sheep in each growth stage were under the same feeding management and nutrition conditions.Blood samples were collected from all experimental animals, following which they were fully mixed with anticoagulant and stored at −80 °C. Simultaneously, the body size traits of the experimental animals were recorded, including the wither height, body length, chest circumference, and body weight of the Chaka sheep, as well as the body length, chest width, wither height, chest depth, chest circumference, cannon bone circumference, and height at the hip cross of the Small-Tailed Han sheep. To reduce random errors in this experiment, the same person measured and recorded the same trait.LRRC8B gene sequence , which the NCBI database published, was referred to, and gene-specific primers were designed using Primer. The specific primers were submitted to Sangon Bioengineering Co., Ltd  for synthesis  The 5xpClone007 Versatile Simple Vector Mix was developed to construct the T Vector (junction site: CCCTT AAGGG). The sixth step was the transformation of connection products. The seventh step was to inoculate the transformed product into a bacterial petri dish. Step eight was to select monoclones, and second generation sequencing was used for verification.http://analysis.bio-x.cn (accessed on 10 March 2021)) to analyze the HWec (Hardy–Weinberg equilibrium constant), Ho (homozygosity), He (heterozygosity), PIC (polymorphism information content), genotype frequency, and allele frequency of LRRC8B gene polymorphisms in the sheep population. All data were presented as means ± SE [mn = μ + Gm + en, where μ was the average population value, Gm was the genotype fixed effect, and en was the stochastic error.SPSS23.0 software was used to conduct association analysis between the body size data of the Chaka and Small-Tailed Han sheep populations and the InDel typing results. We used the website SHEsis  and homozygous deletion (DD), and the DNA sequence is consistent with the electrophoretic figure (The 4 bp mutation site of the c figure .p < 0.05). Furthermore, He was 0.409 and PIC was 0.409, showing moderate polymorphism. In the Small-Tailed Han sheep, the frequency of the D gene was 0.795, so it belonged to the dominant gene in the HWec (p < 0.05), whereas He was 0.326 and PIC was 0.326, so it belonged to moderate polymorphism.The results of the genotyping were statistically analyzed to calculate the HWec, Ho, He, PIC, genotype frequency, allele frequency, etc., which are presented in a table . In the LRRC8B gene. However, no obvious associations were found among these four traits (LRRC8B gene. The results showed that there was a significant association with chest depth (p < 0.05) with a p value of 0.044. Additionally, the DD genotype of the Small-Tailed Han sheep was better than their ID genotype. However, no significant association was found with the other six body conformation traits , with the other presumably being a heterologous double strand [In this study, a tiny InDel mutation of the sheep Heterologous double strands are formed from the complementary pairing of the single-stranded bases of the double-stranded molecules of both parents. However, due to the different sources of the two single DNA strands, the bases are not completely paired, and it is easy to form an unpaired ring structure. Therefore, to verify the heterologous double-stranded structure of this experiment, a TA cloning experiment was conducted. The sequencing results showed not only ID and DD genotypes but also many sequences that were significantly different from the PCR products, which confirmed our speculation about heterologous double chains.LRRC8B gene and body conformation traits  in the 269 Chaka sheep population. Surprisingly, the ID genotype had better traits than the DD genotype, with the best association being for body length, followed by body weight and wither height, and the worst association being for chest circumference. We speculated that individuals with ID genotype could regulate the expression of LRRC8B or other genes, thus promoting the growth and development of Chaka sheep. Among the 149 Small-Tailed Han sheep population, the InDel of LRRC8B gene was significantly correlated with the chest depth of Small-Tailed Han sheep, and the association coefficients reached 0.044. The traits of DD genotype were superior to that of ID genotype. However, InDel of LRRC8B gene did not show significant association with other six traits . The dominant traits of ID genotype individuals included body length, wither height, cannon bone circumference, and height at hip cross, whereas the dominant traits of DD genotype individuals included chest width and chest circumference. The best association was cannon bone circumference, and the worst was body length. The HWec of Chaka sheep and Small-Tailed Han sheep were both lower than 0.05, indicating that the gene frequency and genotype frequency of the two sheep breeds were in a state of balance. The population genetic diversity showed a positive association with polymorphism information content. The PIC and He of Chaka sheep and Small-Tailed Han sheep were both greater than 0.25 and less than 0.5, which belonged to the moderate polymorphism level. The genetic variation was rich; we could increase the mining of beneficial mutations and promote the breeding process of Chaka sheep and Small-Tailed Han sheep.Our results showed that there was no significant association between the InDel of PLAG1 and SIRT4 genes are significantly correlated with the body conformation traits of several cattle breeds [Cry2 and GDF9 genes have been found to be significantly correlated with the litter size of sheep and goats, respectively [Oct4 gene is associated with the reproductive traits of male piglets [GOLGB1 gene is significantly correlated with the growth and carcass traits of chickens [FecB gene is significantly correlated with the number of offspring produced in Chinese Australian White sheep [LRRC8B gene was significantly correlated with the chest depth of Small-Tailed Han sheep, and the DD genotype individuals showed better performance. The insertion–deletion mutation of the CREB1 gene, which is involved in the regulation of fat metabolism in sheep adipose tissue, is also significantly related to the body conformation traits of sheep [In the field of livestock and poultry breeding, InDel molecular marker technology has made remarkable achievements, one example of which shows that the InDel mutations of e breeds ,39. In aectively ,40. Furt piglets , whereaschickens . In addite sheep . Similarof sheep . These rLRRC8B gene is associated with other unchecked traits. Therefore, the InDel molecular marker still has great application prospects for animal breeding. Furthermore, the Small-Tailed Han sheep is an excellent local sheep breed in China with high performance and can be used as an ideal parent candidate in meat production. In this study, it was found that the mutation of the LRRC8B locus at 74,215 bp–74,218 bp is significantly associated with chest depth in Small-Tailed Han sheep (p < 0.05), and chest depth is closely and positively related to sheep body condition. That is, the deeper the chest, the fatter the sheep. However, further research is needed to explain this.Chaka sheep have adapted to the environment of Chaka Salt Lake over time, forming a unique gene pool with abundant alleles . AlthougLRRC8B gene and the chest depth of Small-Tail Han sheep, we plan to construct LRRC8B gene interference and overexpression vector and transfect sheep muscle primary cells to detect the growth and development of cells (such as cell proliferation and differentiation). Meanwhile, ESEfinder 3.0 online software was used to predict the splicing point changes of the pre-mRNA of the gene, and Phyre2 software was used to predict the protein structure and function of the gene.In order to test the association between the InDel site of LRRC8B gene, most of which have been in the field of medical research and are widely used in cancer treatment [LRRC8B gene and the body conformation traits of Chaka and Small-Tailed Han sheep.To date, there have been few functional studies on the reatment . In addiLRRC8B gene in the Small-Tailed Han sheep population and suggested that it can be used as a molecular marker to improve meat yield.In conclusion, this study found a new InDel of the