OBJECTIVE To evaluate the efficacy of oral and facial muscle functional training in treating adult obstructive sleep apnea(OSA)and to identify clinical indicators influencing treatment outcomes.METHODS Through a prospective cohort study,patients diagnosed with OSA in the study unit were recruited to undergo a 3-month myofunctional therapy,including soft palate-related muscles,tongue muscles,buccal muscles,and labial muscles in multiple muscle groups,once a day,five times a week,with the use of offline clinic guidance,and the APP program video follow up training for effective training.Data were collected on multiple dimensions including physical signs,sleep breathing monitoring parameters,and airway measurements from imaging studies.Treatment efficacy was assessed by comparing subjective and objective sleep indicators before and after training.Patients were categorized into effective and ineffective groups based on treatment outcomes.Differences in baseline clinical indicators between these groups were analyzed using univariate and multivariate regression analyses.RESULTS The study finally included 58 people,51 males and 7 females,age(38.36±8.96)years,BMI(27.14±3.68)kg/m2,AHI of the enrolled patients was reduced from(31.27±22.28)times/h pre-training to(26.27±21.38)times/h post-training,the minimum oxygen saturation was increased from(78.43±10.07)%to(80.50±10.06)%,snoring index decreased from(62.80±75.20)times/h to(36.40±43.19)times/h,and ESS score decreased from 7.00±5.31 pre-training to 5.50±3.17.By comparing the effective and ineffective groups,it was found that there was a statistically significant difference in the tongue position and ESS scores between the two groups(both P<0.05),while no significant differences were found in gender,age,neck circumference,posterior soft palate area,uvula area,posterior tongue area,or posterior epiglottic area(all P>0.05).Univariate logistic regression analysis indicated that tongue position,AHI,and ESS scores were factors affecting the efficacy of oral and facial muscle function training.Multivariate regression analysis revealed that AHI was an independent prognostic factor for this training in OSA patients.CONCLUSION Oral and facial muscle function training can improve both subjective and objective sleep breathing indices in OSA patients.Tongue position,AHI,and ESS scores may serve as prognostic factors for OSA treatment,aiding in guiding subsequent individualized intervention therapies.

Gastrointestinal motility disorder is an important cause of digestive system diseases. Patients often suffer from nausea， vomiting， gastric retention， gastroparesis， constipation， and many other symptoms， and their quality of life is seriously reduced. Prokinetic agents are routinely used in clinical practice， but their long-term use is prone to problems such as reduced efficacy and increased adverse reactions. Since the incidence of gastrointestinal diseases has continued to rise globally in recent years， there is an urgent need for clinical development of safe and effective treatment strategies. Aurantii Fructus， a traditional Chinese medicine， has the effect of smoothing Qi and eliminating distention， and it has been used to treat gastrointestinal diseases for thousands of years. In modern clinical practice， it is mainly used for the treatment and auxiliary treatment of various gastrointestinal diseases such as functional dyspepsia， functional constipation， and irritable bowel syndrome. The efficacy is remarkable， and no adverse reactions have been reported at conventional doses. Therefore， it can greatly improve the symptoms of patients with gastrointestinal diseases and improve their quality of life. Modern research has revealed that there are many active components in Aurantii Fructus， among which flavonoids have the highest content and the most types. Flavonoids are the main active components in Aurantii Fructus to regulate gastrointestinal motility. Aurantii Fructus and its active components can affect gastrointestinal hormones， neural pathways， Cajal mesenchymal cells， and other multiple mechanisms. They can adjust gastrointestinal motility and correct gastrointestinal motility disorders， showing potential application value in the treatment of gastrointestinal motility disorders. However， a comprehensive analysis of Aurantii Fructus in this aspect is still lacking. This study summarized the pharmacological activities of active components of Aurantii Fructus extract and its flavonoids， volatile oils， alkaloids， and coumarin on the regulation of gastrointestinal motility and explored the latest research progress on its mechanism. Finally， the adverse reactions of Aurantii Fructus were summarized. It aims to provide a scientific basis for the research and clinical application of Aurantii Fructus and its active components in the regulation of gastrointestinal motility.

Objective:To observe the effects of moxibustion on the levels of glucose-6-phosphate dehydrogenase(G6PD)and reduced nicotinamide adenine dinucleotide phosphate(NADPH)in the plasma and spleen and the CD4+T-cell number in the spleen of rats with adjuvant arthritis,thus to explore the mechanism in rheumatoid arthritis(RA)treatment with moxibustion by regulating the CD4+T-cell proliferation through G6PD-mediated pentose phosphate pathway. Methods:Twenty-seven male Sprague-Dawley rats were randomly divided into a blank group,a model group,and a moxibustion group,with 9 rats in each group.Incomplete Freund's adjuvant was used to induce inflammation in the model group and the moxibustion group.The blank group and the model group were not intervened.In the moxibustion group,suspended moxibustion was performed at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 30 min,once a day for 24 times in total.Hematoxylin-eosin staining was used to evaluate the histopathological changes of rat synovial tissue;the swelling degree of the rat toes was observed by measuring the toe volume;G6PD and NADPH in the spleen and plasma were detected by Western blotting and enzyme-linked immunosorbent assay.Flow cytometry was used to detect the CD4+T-cell number in the spleen. Results:Compared with the blank group,the levels of G6PD and NADPH in the plasma and spleen and the CD4+T-cell number in the spleen were significantly increased in the model group(P<0.01 or P<0.05).Compared with the model group,the NADPH level in the spleen and plasma and the CD4+T-cell number in the spleen in the moxibustion group decreased significantly(P<0.05 or P<0.01),and the G6PD level in the plasma decreased significantly(P<0.05),but there was no significant difference in the G6PD level in the spleen(P>0.05). Conclusion:Moxibustion can regulate immunity and improve joint synovial inflammation in RA.The mechanism may be that the G6PD-mediated pentose phosphate pathway reduces the production of metabolite NAPDH in CD4+T cells,thereby inhibiting the proliferation of naive CD4+T cells.

Objectives:To present the epidemiological characteristics of stroke incidence and stroke-related mortality among the whole population in national cardiovascular disease surveillance areas from 2015 to 2019. Methods:Data of stroke incidence and stroke-related mortality from 2015 to 2019 were collected from the China Registry of Cardiovascular Events(China RACE),which was established in 2014,covering 100 counties(cities,districts)in 31 provinces in China.The Joinpoint model was used to analyze the annual percentage changes(APC)and trends of stroke incidence rate.The age-standardized incidence rate(ASIR)was calculated using the Seventh National Census data as the standard population.With annual reported stroke events and stroke-related deaths,the mortality to incidence ratio(M/I)were examined. Results:From 2015 to 2019,an increase of 9.41%(APC=2.12%,95%CI:1.43%-2.82%,Ptrend<0.01)resulted in the overall stroke crude incidence rate(CIR)of 468.48/100 000 in 2019 among the whole population,with relatively higher in male and in rural area.The more sharply elevating of CIR appeared in males(11.26%[APC=2.53%,95%CI:1.83%-3.24%,Ptrend<0.01])rather than in females(7.26%[APC=1.63%,95%CI:0.81%-2.46%,Ptrend<0.01]).Meanwhile,the general ASIR decreased 7.47%(APC=-1.72%,95%CI:-3.23%--0.20%,Ptrend<0.05),reaching 523.82/100 000 in 2019.The females generally showed significant descending trend(9.56%[APC=-2.27%,95%CI:-3.99%--0.52%,Ptrend<0.05]),as well as more reduction than that in the males(15.82%vs.11.40%)in urban area.The crude incidence rate of stroke increased with age.From 2015 to 2019,the CIR in 45-49 age group increased 12.48%(APC=3.18%,95%CI:1.67%-4.72%,Ptrend<0.01),compared with an reduction of 15.76%(APC=-4.39%,95%CI:-7.63%--1.04%,Ptrend<0.05)in 80-84 age group.Over the monitoring years,the overall M/I was 0.19,with an age-specific U-shaped distribution.The lowest of M/I(0.10)appeared in those aged 50-54 and 55-59,while the highest(0.45)detected in those aged 85 and over.The M/I of all age in urban areas were consistently lower than that in rural areas. Conclusions:Stroke incidence burden increased from 2015-2019 in the national surveillance areas in China,along with the unfavorable geographic diversity and age-specific divergence.Further efforts are required to improve health care covering all ages and regions in China to reduce the incidence of stroke and stroke-related mortality.

Objectives:The present study aims to investigate the incidence and mortality feature of acute myocardial infarction(AMI)from 2015 to 2019 in China by utilizing national registry data. Methods:Data of AMI incidence and mortality in the surveillance area during 2015 to 2019 were abstracted from China Registry of Acute Cardiovascular Event(China RACE),which was established in 100 counties from 31 provincial regions in China.Incidence rate,age standardized incidence rate(ASIR)and mortality to incidence ratio(M/I)was estimated in AMI cases.A Joinpoint regression was executed and annual percent change(APC)was examined to identify trends in incidence. Results:From 2015 to 2019,a total of 257 686 acute myocardial infarction incidence and 149 169 deaths were registered.The annual incidence rate of AMI in 2019 was 82.76 per 100 000.Over the study period,the incidence rate of AMI increased by 6.05%for men(APC=1.30%,95%CI:0.56%to 2.02%)but decreased by 11.80%for women(APC=-3.10%,95%CI:-4.54%to-1.68%),resulting a steady trend for AMI crude incidence rate for the overall population.The overall ASIR of AMI declined by 16.59%(APC=-4.32%,95%CI:-5.32%to-3.34%)from 113.68 per 100 000 in 2015 to 94.82 per 100 000 in 2019.The ASIR of AMI declined by 11.04%(APC=-2.72%,95%CI:-3.78%to-1.67%)for men,23.96%(APC=-6.56%,95%CI:-8.57%to-4.58%)for women,12.57%(APC=-3.08%,95%CI:-6.01%to-0.08%)for the urban areas,and 19.24%(APC=-5.18%,95%CI:-10.19%to 0.03%)for rural areas respectively.The incidence rate of AMI increases gradually with age in both men and women.The incidence of AMI in urban men of 35-44 and 45-54 year age groups increased by 77.16%(APC=13.52%,95%CI:3.29%to 24.57%)and 26.36%(APC=5.71%,95%CI:-0.95%to 12.68%)over time.However,the incidence of AMI fell in the population above 65 year old,by 26.58%(APC=-6.68%,95%CI:-11.98%to-1.01%),19.85%(APC=-5.64%,95%CI:-11.57%to 0.65%)and 14.53%(APC=-4.44%,95%CI:-7.75%to-1.04%)in the 65-74 year age,75-84 year age and≥85year age groups respectively from 2015 to 2019.The mortality to incidence ratio of AMI was 0.58 over time,higher in women than in men,and higher in rural areas than in urban areas.The M/I ratio of AMI decreased from 0.62 in 2015 to 0.52 in 2019(APC=-4.28%,95%CI:-5.75%to-2.83%).There was a declined trends in M/I of AMI in urban residents of both male and female,and in the rural male residents(all P<0.05),while a steady trend in the rural female residents(P>0.05). Conclusions:The overall incidence of AMI remains steady during 2015 to 2019 in the national surveillance areas in China.Yet,downward trends in elder and female residents and increased trend in middle-aged urban males in AMI incidence are observed.The mortality of AMI in these period are age,sex and urban-rural dependent.Targeted mitigation strategies on AMI prevention and treatment need to be strengthened to reduce its incidence and mortality.

Macrophages, as important immune cells, are involved in the key processes that maintain the homeostasis of intrahepatic microenvironment. Recent studies have shown that different liver diseases can induce macrophage polarization (MPP) and form M1 and M2 phenotypes with mutual antagonism. The former promotes the clearance of pathogens and inhibits tumor progression, while the latter exerts an anti-inflammatory effect and promotes tissue repair. However, there are significant differences in the mechanism of action and phenotypic switching of MPP in different liver diseases or at different pathological stages of the disease. This article focuses on the origin and polarization characteristics of intrahepatic macrophages and summarizes the research advances in the role of MPP in the pathogenesis and therapeutic drugs of non-neoplastic liver diseases such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and liver fibrosis, in order to explore the potential of MPP in regulating the immune response and inflammatory response of liver diseases.

Background and Objectives: Manipulating different signaling pathways via small molecules could efficiently inducecardiomyocytes from human induced pluripotent stem cells (hiPSC). However, the effect of transcription factors on the hiPSC-directed cardiomyocytes differentiation remains unclear. Transcription factor, p53 has been demonstrated indispensable for the early embryonic development and mesendodermal differentiation of embryonic stem cells (ESC).We tested the hypothesis that p53 promotes cardiomyocytes differentiation from human hiPSC. Methods: and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, we demonstrated that forced expression of p53 in hiPSC remarkably improved the differentiation efficiency of cardiomyocytes from hiPSC, whereas knockdown endogenous p53 decreased the yield of cardiomyocytes. This p53-mediated increased cardiomyocyte differentiation was mediated through WNT3, as evidenced by that overexpression of p53 upregulated the expression of WNT3, and knockdown of p53 decreased the WNT3 expression. Mechanistic analysis showed that the increased cardiomyocyte differentiation partially depended on the amplified mesendodermal specification resulted from p53-mediated activation of WNT3-mediated Wnt signaling. Consistently, endogenous WNT3 knockdown significantly ameliorated mesendodermal specification and subsequent cardiomyocyte differentiation. Conclusions These results provide a novel insight into the potential effect of p53 on the development and differentiation of cardiomyocyte during embryogenesis.

Objective To explore the diagnostic value ofcerebrospinal fluid (CSF) lactic acid (LA) level in bacterial meningitis after craniotomy for cerebral hemorrhage in adults.Methods The clinical data of 162 patients with cerebral hemorrhage,admitted to and accepted craniotomy in our hospital from April 2013 to April 2018,were retrospectively collected;patients were divided into infected group (n=75) and non-infected group (n=87) according to whether postoperative bacterial meningitis occurred;univariate analysis was used to compare the differences of CSF-LA concentration and other indicators of CSF between patients of the two groups;multivariate Logistic regression analysis was used to screen the independent factors affecting the occurrence of postoperative bacterial meningitis;receiver operating characteristic (ROC) curve was used to analyze the predictive values of CSF-LA and other indicators in postoperative bacterial meningitis.Furthermore,17 patients with positive bacterial CSF were divided into Gram-positive (G+) bacteria group (n=9) and Gram-negative (G-) bacteria group (n=8);the predictive values of CSF-LA and other indicators for postoperative meningitis of G-bacteria patients were analyzed in the same way.Results (1) The CSF-LA concentration in infected group ([6.3±2.8] mmol/L) was significantly increased as compared with that in non-infected group ([3.3±1.6] mmol/L,P＜0.05);the results of multivariate Logistic regression analysis showed that CSF-LA was an independent influencing factor for postoperative bacterial meningitis (odd ratio=l.547,95％ confidence interval:1.029-2.326,P=0.036);ROC curve results revealed that the area under the curve of CSF-LA concentration in the diagnosis of bacterial meningitis after craniotomy was 0.854 (95％ confidence interval:0.790-0.904),and the optimal cut-off value was 4.61 mmol/L,with sensitivity of 69.3％,specificity of 92.0％,positive predictive value of 88.1％ and negative predictive value of 77.7％.(2) The CSF-LA concentration in G-bacteria group ([9.9±2.9] mmol/L) was significantly increased as compared with that in G+ bacteria group ([5.2±3.1] mmoi/L,P＜ 0.05);ROC curve results revealed that,in patients with positive bacterial CSF,the area under the curve of CSF-LA concentration in diagnosis of meningitis with G-bacteria after craniotomy was 0.861 (95％ confidence interval:0.610-0.978),and the optimal cut-off value was 7.20 mmol/L with sensitivity of 87.5％,specificity of 88.9％,positive predictive value of 87.5％,and negative predictive value of 88.9％.Conclusion Detection for concentration of CSF-LA can help predicting bacterial meningitis afier craniotomy for cerebral hemorrhage and identify G+ and G-bacteria meningitis.

Objective To screen and analyze nucleotide variants in 5'-untranslated region(5'-UTR)in voltage-gated sodium channel α1-subunit gene(SCN1A)in patients with Dravet syndrome and to evaluate the association of the variants with disease.Methods Peripheral blood of 24 patients with Dravet syndrome and 100 unrelated normal persons were collected and genomic DNA was extracted.PCR-sequencing of SCN1 A 5'-UTR in these DNA was performed.To evaluate the possibility of mutation inducing disease,bioinformatics analysis was applied to analyze the conservation of the sequences around the mutation site and predict the potential transcription elements.Results The nucleotide variant of 166.642.520G→A in exon 2 was identified in two patients,but not in normal controls.The mutation was a de novo mutation in a patient with early-onset.In the second proband,the mutation was also carried by his clinically asymptomatic mother.The nucleotide site 166.642.520 was moderately conserved in mammals(62.5%).The average nucleotide identity rate between human and other mammals species in the region adjacent to 166.642.520 was 88.5%.Two potential transcription regulatory elements were predicted on the sequence with the mutation of 166.642.520G>A,and only one on the sequence with wild-type.Conclusions The mutation 166.642.520G>A may be associated with Dravet syndrome and further studied should be performed to verify it and demonstrate its pathogenic mechanisms.

Objective To study the sodium channel α1-subunit (SCN1A) gene in a pair of monozygotic twins with borderland severe myoclonic epilepsy in infancy (SMEB) and its characteristic of clinical manifestations. Methods The clinical features of 2 monozygotic twins were summarized. All 26 exons of SCNIA genes were screened with denaturing high performance liquid chromatography (DHPLC), and direct sequence analysis was performed on those with abnormal elution peak. Results The proband and her sister showed typical clinical features of SMEB. The same heterozygous mutations on exon 26 which caused the related amino acid change were found among them (c. 5348C > T, A1783E). Conclusion Monozygotic twins with similar clinical phenotype of SMEB have same SCN1A gene mutation.