ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

Objective:To investigate the disease-modifying effect of long-course use of Omalizumab (OMZ) on children and adolescents with allergic asthma.Methods:Retrospective cohort study.The clinical data of 66 children with moderate to severe allergic asthma treated with OMZ in the Department of Pediatrics, the Second Hospital of Tianjin Medical University from April 2019 to June 2024 were analyzed.According to the course of OMZ, the patients were divided into a short course group (33 cases), a medium course group (21 cases), and a long course group (12 cases).The courses of treatment of the 3 groups were 6-<12, 12-<24 and 24 months or more, respectively.Pulmonary ventilation functions [including the percentage of forced expiratory volume in the first second to the expected value (FEV 1%pred), the peak expiratory flow rate to the expected value (PEF%pred), and the maximum mid-expiratory flow to the expected value (MMEF%pred)], fractional exhaled nitric oxide (FeNO) and the absolute value of peripheral blood eosinophils (EOS) were analyzed before and after OMZ treatment.Moreover, whether allergic asthma and comorbidities such as allergic rhinitis (AR), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU) were controlled was explored.Changes in inhaled corticosteroids (ICS) and serum total immunoglobulin E (TIgE) levels were measured.The paired t-test was used for testing measurement data with normal distribution, and the rank sum test for testing non-normally distributed data. Results:(1)Changes of pulmonary ventilation function, FeNO and EOS: the pulmonary ventilation function in the short course group, the FEV 1%pred and MMEF%pred in the medium course group, and the PEF%pred and MMEF%pred in the long course group were improved compared with those at baseline (all P<0.05).FeNO levels in all the 3 groups decreased, compared with those at baseline (all P<0.05).There was no significant difference in peripheral blood EOS between the 3 groups compared with those at baseline (all P>0.05).(2)Control status of allergic asthma and comorbidities: the Asthma Control Test/Childhood Asthma Control Test (ACT/C-ACT), Asthma Control Questionnaire (ACQ) scores and the visual analogue scores (VAS) of rhinitis improved in all 3 groups, compared with those at baseline (all P<0.05).Among 4 patients complicated with AD, 3(75.0%) showed decreased Scoring Atopic Dermatitis Index(SCORAD) scores, compared with those at baseline.Of the 6 children complicated with CSU, 5(83.3%) did not develop rash after injection.(3)Frequency of acute exacerbations of asthma: the number of acute exacerbations of asthma after treatment was lower than that before treatment in all the 3 groups (all P<0.05).The number of attacks in the long course group was decreased in the third year, compared with that in the first year ( P<0.05).(4)The ICS consumption: the ICS consumption in all the 3 groups was significantly decreased, compared with that at baseline (all P<0.05).Six patients (28.6%) in the medium course group had no recurrence within 1 year after stopping ICS therapy.One of the 7 patients (14.3%) in the long course group had stopped ICS for more than 2 years, and 3 patients (42.9%) had stopped ICS for more than 1 year.These 4 children had no recurrence.(5)The change of TIgE: in the short and medium course groups, serum TIgE levels at the end of treatment were higher than those at baseline (all P<0.05).The serum TIgE level in the second year of treatment was higher than that at baseline in the long course group ( P<0.05).The serum TIgE level in the third year of treatment was decreased, compared with that in the second year ( P<0.05). Conclusions:OMZ can improve lung function and FeNO levels, reduce the incidence of acute exacerbations of asthma, and lower ICS usage in children.At the same time, it can also improve the allergic diseases AR, AD and CSU.The prolonged treatment of OMZ can bring long-term sustained benefits to children.The changes in serum TIgE and FeNO levels may suggest that the long-term application of OMZ plays a disease-modifying role in allergic asthma.

Objective:To investigate the disease-modifying effect of long-course use of Omalizumab (OMZ) on children and adolescents with allergic asthma.Methods:Retrospective cohort study.The clinical data of 66 children with moderate to severe allergic asthma treated with OMZ in the Department of Pediatrics, the Second Hospital of Tianjin Medical University from April 2019 to June 2024 were analyzed.According to the course of OMZ, the patients were divided into a short course group (33 cases), a medium course group (21 cases), and a long course group (12 cases).The courses of treatment of the 3 groups were 6-<12, 12-<24 and 24 months or more, respectively.Pulmonary ventilation functions [including the percentage of forced expiratory volume in the first second to the expected value (FEV 1%pred), the peak expiratory flow rate to the expected value (PEF%pred), and the maximum mid-expiratory flow to the expected value (MMEF%pred)], fractional exhaled nitric oxide (FeNO) and the absolute value of peripheral blood eosinophils (EOS) were analyzed before and after OMZ treatment.Moreover, whether allergic asthma and comorbidities such as allergic rhinitis (AR), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU) were controlled was explored.Changes in inhaled corticosteroids (ICS) and serum total immunoglobulin E (TIgE) levels were measured.The paired t-test was used for testing measurement data with normal distribution, and the rank sum test for testing non-normally distributed data. Results:(1)Changes of pulmonary ventilation function, FeNO and EOS: the pulmonary ventilation function in the short course group, the FEV 1%pred and MMEF%pred in the medium course group, and the PEF%pred and MMEF%pred in the long course group were improved compared with those at baseline (all P<0.05).FeNO levels in all the 3 groups decreased, compared with those at baseline (all P<0.05).There was no significant difference in peripheral blood EOS between the 3 groups compared with those at baseline (all P>0.05).(2)Control status of allergic asthma and comorbidities: the Asthma Control Test/Childhood Asthma Control Test (ACT/C-ACT), Asthma Control Questionnaire (ACQ) scores and the visual analogue scores (VAS) of rhinitis improved in all 3 groups, compared with those at baseline (all P<0.05).Among 4 patients complicated with AD, 3(75.0%) showed decreased Scoring Atopic Dermatitis Index(SCORAD) scores, compared with those at baseline.Of the 6 children complicated with CSU, 5(83.3%) did not develop rash after injection.(3)Frequency of acute exacerbations of asthma: the number of acute exacerbations of asthma after treatment was lower than that before treatment in all the 3 groups (all P<0.05).The number of attacks in the long course group was decreased in the third year, compared with that in the first year ( P<0.05).(4)The ICS consumption: the ICS consumption in all the 3 groups was significantly decreased, compared with that at baseline (all P<0.05).Six patients (28.6%) in the medium course group had no recurrence within 1 year after stopping ICS therapy.One of the 7 patients (14.3%) in the long course group had stopped ICS for more than 2 years, and 3 patients (42.9%) had stopped ICS for more than 1 year.These 4 children had no recurrence.(5)The change of TIgE: in the short and medium course groups, serum TIgE levels at the end of treatment were higher than those at baseline (all P<0.05).The serum TIgE level in the second year of treatment was higher than that at baseline in the long course group ( P<0.05).The serum TIgE level in the third year of treatment was decreased, compared with that in the second year ( P<0.05). Conclusions:OMZ can improve lung function and FeNO levels, reduce the incidence of acute exacerbations of asthma, and lower ICS usage in children.At the same time, it can also improve the allergic diseases AR, AD and CSU.The prolonged treatment of OMZ can bring long-term sustained benefits to children.The changes in serum TIgE and FeNO levels may suggest that the long-term application of OMZ plays a disease-modifying role in allergic asthma.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To obsere the clinical efficacy of Hall technology in the treatment of primary molar caries in children with au-tism.Methods:80 children aged 4-8 years with primary molar caries,40 normal children and 40 children with autism,with a total of 153 primary molars.The normal and the autism children were respectively divided into 2 groups(n=20)randomly.The normal children were grouped into resin filling(CR)of 38 teeth and Hall technology group(CH)of 39 teeth,the autistic children were grouped into resin filling(AR)of 37 teeth and Hall technology group(AH)of 38 teeth.Corresponding treatment was given to the pa-tients in the groups.The duration of oral treatment time,Frankl scores,Houpt scores and parental satisfaction scoves were compaired among groups.The patients were followed up for 6,12,18 and 24 months and the treatment outcomes were compared among groups.Results:There was no statistically difference between CH group and AH group in terms of operating time,compliance,Houpt score and follow-up effects(P＞0.05).The satisfaction of parents in the AR group was the lowest(P＜0.05).Hall technology treatment re-mained effective rate was higher than resin filling at the 24 month follow-up(P＜0.05).Conclusion:Hall technology is more effective than traditional resin filling in the treatment of primary molars caries in children with autism.

ObjectiveTo confirm the clinical efficacy and safety of Yishen Yangxin Anshen tablets in the treatment of insomnia （heart-blood deficiency and kidney-essence insufficiency syndrome）. MethodA randomized block， double-blind， placebo-controlled， multi-center clinical trial design method was adopted， and a total of 480 patients with insomnia due to deficiency of heart blood and insufficiency of kidney essence （treatment group-control group 3∶1） from seven hospitals （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， The First Clinical Hospital， Jilin Province Academy of Traditional Chinese Medicine（TCM）， The Second Affiliated Hospital of Liaoning University of TCM， The First Affiliated Hospital of Henan University of Chinese Medicine， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine） were enrolled. The treatment group was given Yishen Yangxin Anshen tablets and the control group received placebo tablets （4 tablets/time， 3 times/day， 4 weeks of administration， 4 weeks of follow-up after drug withdrawal）. The sleep dysfunction rating scale （SDRS） score， pittsburgh sleep quality index （PSQI） score， TCM， polysomnography （PSG） indicators from four hospital （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine）， and other efficacy indicators were compared between the two groups before and after treatment. Through general physical examination， laboratory examination， and observation of adverse events， the safety of the drugs was evaluated. ResultThe baseline indexes of the two groups showed no significant difference and thus the two groups were comparable. After treatment， the total score of SDRS in the treatment group was lower than that in the control group （P<0.01）. After drug withdrawal for 4 weeks， the total score of SDRS demonstrated no significant change in the treatment group as compared with that at the end of treatment， indicating that the rebound change of curative effect was not obvious. After treatment， the total score of PSQI in the treatment group decreased as compared with that in the control group （P<0.01）， and the change of total score of PSQI in the treatment group was statistically significant （P<0.05） after drug withdrawal for 4 weeks but small， indicating that the rebound change of curative effect was not obvious. After treatment， the total effective rate about the TCM symptoms in the treatment group was higher than that in the control group （χ²=137.521，P<0.01）. After treatment， the disappearance rates of single indexes in the treatment group， such as difficulty in falling asleep， easily waking up after sleeping， early awakening， short sleep time， dreamfulness， palpitation， forgetfulness， dizziness， mental fatigue， and weakness of waist and knee， increased compared with those in the control group （P<0.01）. After treatment， the treatment group demonstrated fewer awaking times （AT）， longer total sleep time （TST）， lower ATA/TST ratio， and higher sleep efficiency （%） than the control group （P<0.05）. No abnormal value or aggravation related to drugs was observed in either group. The incidence of adverse events in the treatment group and the control group was 5.57% and 8.40% respectively. No serious adverse events or adverse events leading to withdrawal happened in either group. ConclusionYishen Yangxin Anshen tablets is effective and safe for patients with insomnia of deficiency of heart-blood and insufficiency of kidney-essence.

Allergen immunotherapy(AIT)is an effective treatment for allergic diseases that have been used for more than a century.At present, AIT is administered in two main ways: subcutaneous immunotherapy(SCIT)and sublingual immunotherapy(SLIT), which aims to induce immune tolerance to allergens and provide long-term clinical benefit to patients.The effectiveness of AIT has been confirmed and the research on its mechanism has been deepened, and AIT combined with biological agents has been widely used in clinical practice.

OBJECTIVE To study the secondary metabolites of the endophytic fungus Fusarium sp. HSL-3 isolated from Hainan Mangrove and screen their anti-inflammatory and anti-tumor activities. METHODS This fungus was fermented statically by using rice medium, and the secondary metabolites of the fungus were isolated and purified by column chromatography and HPLC. Structures indentification of the ortained compounds was carried out through MS and NMR. RESULTS Eight compounds were respectively isolated and identified as follows:lateritin(1), 4-carbomethoxy-6-hydroxy- 2-quinolone(2), 3,5-dimethoxydihydro-fusarubin D(3), anhydrofusarbin(4), 3,3'-methylene-bis(4-hydroxybenzaldehyde)(5), crypticin B(6), vanillyl alcohol(7) and 3,4-dihydroxyphenylaceticacid(8), among which, compounds 2 and 5 were isolated from the genus Fusarium for the first time. Compounds 3 and 5 showed good anti-inflammatory activity on RAW264.7 cells with the inhibition rate of NO at 50 µmol·L-1 were 87% for compound 3 and 71% for compound 5, while compound 1 showed significant cytotoxic activity against human non-small cell lung cancer cell line A549, among which the IC50 value was (7.92±0.27) µmol·L-1. CONCLUSION Compounds 3 and 5 isolated from endophytic fungus Fusarium sp. HSL-3 isolated from Hainan Mangrove show strong anti-inflammatory activity, while compound 1 shows significant anti-tumor activity.

Bronchial asthma(asthma)is a common chronic airway inflammatory disease in children, most of which are allergic asthma.Allergen immunotherapy can change the natural course of asthma, and has certain efficacy in controlling asthma symptoms, reducing airway hyperresponsiveness and reducing the use of control drugs.It is the treatment for the cause.The most common allergen immunotherapy treatments are subcutaneous immunotherapy and sublingual immunotherapy.This article reviews the effectiveness of subcutaneous immunotherapy in the treatment of children with asthma, and focuses on the effective evaluation indicators and potential biomarkers that can be used as reference in clinical practice.