Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

ObjectiveTo monitor the real-time changes in ammonia concentration in the laboratory animal facility environment before, during, and after the air conditioning system stops supplying air, so as to provide a basis and reference for developing emergency plans for the shutdown of the air conditioning system. MethodsThe laboratory animal facilities of the Wuhan Institute of Biological Products were used as the research object. Ammonia concentration detectors were used to monitor ammonia concentration continuously in the environment of conventional rabbit production facility, SPF hamster production facility, and SPF guinea pig experimental facility before and after the passive shutdown due to repairs and active maintenance shutdown of the air conditioning system, as well as the time for the ammonia concentration to return to daily levels after resuming air supply. ResultsUnder both shutdown modes of the air conditioning system, the trend of ammonia concentration changes in different laboratory animal facilities was consistent, showing a rapid increase after shutdown and a rapid decrease after resuming air supply. Under active maintenance shutdown, the maximum ammonia concentrations in the conventional rabbit production facilities, SPF hamster production facilities, and SPF guinea pig experimental facilities were 9.81 mg/m³, 14.27 mg/m³, and 6.98 mg/m³, respectively. Within 12 minutes after resuming air supply, ammonia concentration could return to normal daily levels. Under passive long-term shutdown, ammonia concentration value was positively correlated with the duration of air supply suspension. As the shutdown duration increased, ammonia concentration continued to increase. The maximum ammonia concentration values in the three facilities occurred at 88 minutes (38.06 mg/m³), 40 minutes (18.43 mg/m³), and 34 minutes (15.61 mg/m³) after air supply suspension, respectively.Within 11 minutes after resuming air supply, ammonia concentration could return to normal daily levels. ConclusionShutdown of the air conditioning system causes a rapid increase in ammonia concentration in laboratory animal facilities, and the rise in ammonia concentration is positively correlated with the duration of air supply suspension. Therefore, when an emergency shutdown of the air-conditioning system is required due to maintenance or other reasons, backup fans should be provided in accordance with the requirements of GB 50447-2008 "Architectural and Technical Code for Laboratory Animal Facilities". Older facilities should make adequate preparations and develop a scientifically sound emergency plan.

ObjectiveThe proteome of biological evidence contains rich genetic information, namely single amino acid polymorphisms (SAPs) in protein sequences. However, due to the lack of efficient and convenient analysis tools, the application of SAP in public security still faces many challenges. This paper aims to meet the application requirements of SAP analysis for forensic biological evidence’s proteome data. MethodsThe software is divided into three modules. First, based on a built-in database of common non-synonymous single nucleotide polymorphisms (nsSNPs) and SAPs in East Asian populations, the software integrates and annotates newly identified exonic nsSNPs as SAPs, thereby constructing a customized SAP protein sequence database. It then utilizes a pre-installed search engine—either pFind or MaxQuant—to perform analysis and output SAP typing results, identifying both reference and variant types, along with their corresponding imputed nsSNPs. Finally, SAPTyper compares the proteome-based typing results with the individual’s exome-derived nsSNP profile and outputs the comparison report. ResultsSAPTyper accepts proteomic DDA mass spectrometry raw data (DDA acquisition mode) and exome sequencing results of nsSNPs as input and outputs the report of SAPs result. The pFind and Maxquant search engines were used to test the proteome data of 2 hair shafts of2 individuals, and both obtained SAP results. It was found that the results of the Maxquant search engine were slightly less than those of pFind. This result shows that SAPTyper can achieve SAP fingding function. Moreover, the pFind search engine was used to test the proteome data of 3 hair shafts from 1 European person and 1 African person in the literature. Among the sites fully matched by the literature method, sites detected by SAPTyper are also included; for semi-matching sites, that is, nsSNPs are heterozygous, both literature method and SAPTyper method had the risk of missing detection for one type of the allele. Comparing the analysis results of SAPTyper with the SAP test results reported in the literature, it was found that some imputed nsSNP sites identified by the literature method but not detected by SAPTyper had a MAF of less than 0.1% in East Asian populations, and therefore they were not included in the common nsSNP database of East Asian populations constructed by this software. Since the database construction of this software is based on the genetic variation information of East Asian populations, it is currently unable to effectively identify representative unique common variation sites in European or African populations, but it can still identify SAP sites shared by these populations and East Asian populations. ConclusionAn automated SAP analysis algorithm was developed for East Asian populations, and the software named SAPTyper was developed. This software provides a convenient and efficient analysis tool for the research and application of forensic proteomic SAP and has important application prospects in individual identification and phenotypic inference based on SAP.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Objective To evaluate the clinical efficacy of oral use of Jiawei Puji Xiaodu Granules(mainly composed of Lonicerae Japonicae Flos,Forsythiae Fructus,Taraxaci Herba,Violae Herba,Schizonepetae Herba,Arctii Fructus,Gleditsiae Spina,Paeoniae Radix Rubra,Moutan Cortex,and Phragmitis Rhizoma)combined with external application of Xiaozhong Sanjie Ointment(mainly composed of Scutellariae Radix,Coptidis Rhizoma,Phellodendri Chinensis Cortex,and Gleditsiae Spina,etc.)in the treatment of acute tonsillitis in children,and to observe their effects on the immune function and related inflammatory indexes of the patients.Methods A total of 116 children with acute tonsillitis of heat stagnation in the lung and stomach type were randomly divided into the control group and the observation group,with 58 cases in each group.The control group was treated with Cefixime Dispersible Tablets,while the observation group was treated with Jiawei Puji Xiaodu Granules for oral use and Xiaozhong Sanjie Ointment for external application.Both groups were treated for 14 days and then were followed-up for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,white blood cell(WBC)count,T lymphocyte subset CD3+,CD4+,CD8+ and CD4+/CD8+ levels,and serum levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),interleukin 6(IL-6)and C-reactive protein(CRP)in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and time for the disappearance of clinical symptoms were compared between the two groups,and the occurrence of adverse reactions and the recurrence of tonsillitis in the two groups were monitored at the same time.Results(1)During the trial,there were 8 cases falling off in the control group but none case falling off in the observation group,and eventually 50 cases in the control group and 58 cases in the observation group completed the full course of treatment.(2)After 14 days of treatment,the total effective rate of the observation group was 98.28%(57/58),while that of the control group was 90.00%(45/50).The intergroup(tested by rank sum test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the time for the disappearance of sore throat,time for the disappearance of purulent spots,time for subsiding fever and time for the tonsils recovering to normal in the observation group were all significantly shorter than those in the control group(P＜0.05).(4)After treatment,the scores of primary and secondary symptoms and the overall symptom scores in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction of the scores in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the levels of T lymphocyte subset CD3+,CD4+ and CD4+/CD8+ in the two groups were significantly higher(P＜0.05)while the level of CD8 + was significantly lower(P＜0.05)than those before treatment,and the increase in the levels of CD3+,CD4+ and CD4+/CD8+ and the reduction of the CD8+ level of the observation group were significantly superior to those of the control group(P＜0.05).(6)After treatment,the levels of WBC,TNF-α,IL-1β,IL-6 and CRP in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the treatment period,no skin allergy,nausea,vomiting or other gastrointestinal adverse reactions occurred in the two groups,which showed a high degree of safety.(8)The 6-month follow-up showed that the recurrence rate of tonsillitis in the observation group was 5.17%(3/58),which was significantly lower than that of 24.00%(12/50)in the control group,and the difference was statistically significant(χ2 = 8.330,P＜0.05).Conclusion The efficacy of Jiawei Puji Xiaodu Granules combined with Xiaozhong Sanjie Ointment exert notable curative effect for children with acute tonsillitis of heat stagnation in the lung and stomach type.The combined therapy can significantly shorten the duration of the disease,improve the clinical symptoms of the children and effectively reduce the recurrence rate of tonsillitis.The therapeutic mechanism may be related to the enhancement of the immune function and the inhibition of inflammatory response.

Objective To screen differentially expressed microRNAs(miRNAs)in plasma exosomes of active rheumatoid arthritis(RA)patients and healthy controls and conduct bioinformatics analysis for exploring the role and potential clinical application value of miRNAs in the pathogenesis of RA.Methods From January 2023 to April 2023,39 RA patients who visited the Rheumatology and Immunology Department of the Second Affiliated Hospital of Soochow University were selected as the study subjects,while 39 healthy individuals were selected as normal controls.The expression levels of miRNAs in plasma exosomes were detected by Illumina high-throughput sequencing technology,and the differentially expressed miRNAs were obtained by log2(Fold Change)absolute value>1 and P value<0.05.Six miRNAs were selected by the order from small to large P-value for bioinformatics analysis and validated using quantitative real-time fluorescence PCR(qRT-PCR).Results Compared with healthy controls,22 aberrantly expressed miRNAs were detected in plasma exosomes of RA patients,of which 4 were up-regulated and 18 were down-regulated.Among them,miR-30b-5p,miR-144-3p,miR-20a-5p,miR-223-5p,miR-425-3p,and miR-589-5p showed changed significantly.GO and KEGG enrichment analysis indicated that differentially expressed miRNAs may be involved in disease progression through regulation of signaling pathways such as TGF-β and PI3K/AKT,which were related to biological processes such as Th17 differentiation,intercellular interactions,and protein phosphorylation.The qRT-PCR validation results showed that the expression of miR-144-3p and miR-425-3p were significantly reduced in plasma exosomes of RA patients compared to healthy controls(t=3.617,3.595,all P<0.001),while the differences of miR-30b-5p,miR-223-5p,miR-589-5p,and miR-20a-5p expression were not statistically significant(t=1.956,1.331,1.662,1.861,all P>0.05).Conclusion The expression profile of plasma exosomal miRNAs changed in RA patients,which may be involved in disease progression through TGF-β and other signaling pathways.Exosome-derived miR-144-3p and miR-425-3p may be potential serological markers for RA diagnosis.

Objective To analyze the relationship of the volume of 87 brain regions with postnatal age and neurobehavior in full-term neonates.Methods A total of 75 full-term newborns[gestational age(39.38±1.22)weeks;male/female(51/24);postnatal age(11.11±6.67)days]without abnormalities on brain MRI(three-dimensional T1-weighted imaging,3D T1WI)at our hospital between November 2010 and September 2017 were retrospectively included.Based on the template of 87 brain regions,the neonatal brains were divided into 87 brain regions and their volumes were calculated by using V-shape Bottleneck network(VB-Net)deep learning segmentation technique,Pearson partial correlation and regression analysis were used to explore the relationship of the volume of each brain region with postnatal age and neurobehavioral scores.Results After adjusting for gestational age,birth weight,head circumference,body length and sex,66.7％of the regional brain volumes(58/87 brain regions)significantly increased with the postnatal age(correlation coefficient r:0.2-0.7,P＜0.05).The volumes of gray matter in bilateral lentiform nucleus,left caudate nucleus,right occipital lobe,right inferior temporal lobe,and bilateral anterior temporal lobe strongly correlated with the postnatal age(r＞0.50,P＜0.05).The gray matter volume of the right occipital lobe linearly increased with age(slope:100.67),and was positively correlated with behavioral scores(r=0.324,P＜0.01).Conclusion Most of regional brain volumes increase with the postnatal age during the neonatal period,and the fastest growth occurs in primary sensorimotor-related brain regions,presenting the spatial heterogeneity.Partial brain region grows with the development of behavioral ability.

BACKGROUND:After the treatment of femoral shaft fracture with the intramedullary nail,the third fracture open reduction indications are controversial.Some scholars believe that limited open reduction can achieve anatomical reduction,conducive to fracture healing;but some scholars believe that no open reduction of the third fracture still has a high fracture healing rate. OBJECTIVE:To investigate the effect of the circumference and displacement of the third fragment on fracture healing after intramedullary nailing of femoral shaft fractures with the third fragment. METHODS:A retrospective cohort study was conducted to analyze the clinical data of 142 patients suffered a femoral shaft fracture with a third fragment admitted to the Affiliated Lianyungang Hospital of Xuzhou Medical University from February 2016 to December 2021.The fracture were classified into three types according to the circumference of the third fracture with reference to the diaphyseal circumference at the fracture site:type 1 in 71 cases,type 2 in 52 cases,and type 3 in 19 cases.Referring to the diaphyseal diameter,the fractures were classified into three degrees according to the degree of the third fragment displacement:degree I in 95 cases,degree II in 31 cases,and degree III in 16 cases.All patients were treated with femoral interlocking intramedullary nails,and no intervention was performed for the displaced third fragment during the operation.Postoperative follow-up was performed to compare the fracture healing rate,healing time,and the modified Radiographic Union Scale for Tibia at month 9 after surgery in each group.The effect of third fracture fragment circumference and degree of displacement on fracture healing was assessed. RESULTS AND CONCLUSION:(1)All 142 patients were followed up for at least 12 months,with a mean of(14.7±4.1)months,and the overall healing rate was 73.4%.(2)When the third fragment was displaced by degree I,the healing rate,healing time,and modified Radiographic Union Scale for Tibia score at month 9 were not statistically significant among the three sub-groups of circumference classification.(3)When the third fragments were displaced by degree II or III,the healing rate and healing time were not statistically significant among the three subgroups of circumference classification;the modified Radiographic Union Scale for Tibia score at month 9 in the type 1 group was higher than that in the type 2 and 3 groups(P = 0.017).(4)Logistic regression analysis showed that a greater third fragment displacement and circumference were associated with lower fracture healing rates(P<0.05).(5)These findings indicate that in the treatment of femoral shaft fractures with third fragment by intramedullary nails,when the fracture fragment is displaced to degree I,the circumference size has little effect on fracture healing,and no intervention is required during surgery.When the third fragment is displaced to degree II or III and the circumference of which is type 1,a higher modified Radiographic Union Scale for Tibia score can still be obtained with no intervention of the third fragment.However,when the circumference is of type 2 or type 3,it significantly affects the fracture healing.Consequently,intraoperative intervention to reduce the distance of displacement of the fragment is required to lower the incidence of nonunion.The displacement of the third fracture fragments has a greater impact on fracture healing than their circumference.