ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

Objective To analyze the vaccination and respiratory infectious disease infections of children recovering from congenital heart disease(CHD) within one year after discharge from the hospital, and to provide a scientific basis for the development of respiratory infectious disease protection strategies for children recovering from CHD.Methods The children recovering from CHD after cardiac surgery at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, from January to August 2023, were recruited as the subjects, and a follow-up survey on their parents or guardians was conducted one year after discharge to analyze the vaccination and respiratory infectious disease status of the enrolled children.Results A total of 200 children recovering from CHD were followed up, and the mean age was(31. 13 ± 19. 94)months. Among them, 94(47. 00%) were male and 106(53. 00%) were female. Regarding the protection pathways against respiratory infectious diseases, frequent opening of windows and ventilation at home(85. 50%), washing hands with hand sanitizer frequently(77. 00%), and wearing masks for babies in public places(41. 00%) were the main choices, and fewer chose to be able to vaccinate their babies in time when their condition stabilized(18. 00%) and to have other members of the family take the initiative to be vaccinated against influenza or pneumonia(6. 00%), and parents of different literacy levels wearing masks for their babies in public places(χ~2 = 10. 356, P = 0. 013) and being able to vaccinate their babies in time when their condition stabilized(χ~2 = 4. 370, P = 0. 041) exhibited statistically significant differences. Regarding respiratory infectious disease infections, children recovering from CHD mainly suffered from mycoplasma pneumonia(22. 50%) and influenza(12. 50%), with a smaller proportion suffering from whooping cough(1. 50%) and COVID-19(2. 50%), and there were two(66. 67%) hospitalizations for influenza in children at < 37 gestation weeks and two(9. 09%) at ≥ 37 gestation weeks with a statistically significant difference(χ~2 = 6. 512, P = 0. 011).Conclusion Parents of children recovering from CHD have a weak awareness of active vaccination and the construction of a family protection circle, and children recovering from CHD have a higher risk of mycoplasma pneumonia and influenza infections. Health education of parents of children recovering from CHD on vaccine-related knowledge should be strengthened to alleviate parental vaccine hesitancy and increase the coverage rate of respiratory infectious disease-related vaccination in this population.

Objective:To clarify the transitional components in the blood of compound Banlangen Granules; To explore the mechanism of drugs in the treatment of epidemic encephalitis B, hepatitis and parotitis.Methods:The transitional components in blood of compound Banlangen Granules were analyzed by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The regulatory targets and pathways of compound Banlangen Granules in the treatment of epidemic encephalitis B, hepatitis and parotitis were analyzed based on UPLC-MS/MS and network pharmacology.Results:A total of 9 blood components were identified, of which 8 were prototype components, including sucrose, o-aminobenzoic acid, uridine, adenosine, guanosine, indole-3-acetonitrile-2 murine-S-β-D-glucopyranoside and salicylic acid. Through network pharmacological analysis, it was concluded that compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.Conclusion:The 9 blood components of compound Banlangen Granules may treat epidemic encephalitis B, hepatitis and parotitis by regulating lipid and atherosclerosis, insulin resistance, IL-17 and other signal pathways.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective:To develop and validate the Intimate Relationships Happiness Questionnaire(IRHQ).Methods:Firstly,interviews were conducted with 20 participants,investigation were conducted with 100 partici-pants,and vocabulary scoring were conducted with 100 participants formed the originally items.Secondly,801 par-ticipants were recruited to finished the initial scale for items analysis and exploratory factor analysis.Thirdly,480 participants were conducted with the IRHQ,Satisfaction With Life Scale(SLS),Subjective Authentic-Durable Hap-piness Scale(SA-DHS),Chinese Happiness Inventory(CHI)and Marital Happiness Scale(MHS)for confirmatory factor analysis,criterion-related validity and internal consistency analysis.Finally,100 participants were assessed with IRHQ after 2 weeks for test-retest reliability.Results:After items analysis and exploratory factor analysis,29 i-tems were selected as the final scale with a total of four factors that accounted for 63.76％of the variance in all for IRHQ,4 factors including body harmony,mental harmony,fitting-value and sexual relationship satisfac-tion.Confirmatory factor analysis indicated that the four-factor model had a goof structural fit(x2/df=2.89,P＜0.001,TLI=0.93,CFI=0.94,RMSEA=0.04).The scores of IRHQ was positively correlated with the scores of SLS,SA-DHS,CHI and MHS(ICC=0.27-0.72,Ps＜0.001).The internal consistency reliabilities of the total score of the scale and the score of the 4 factors were 0.74,0.73,0.72,0.78 and 0.90.The retest reliabilities were 0.87,0.83,0.88,0.88 and 0.90.Conclusion:The Intimate Relationships Happiness Questionnaire meetsthe psy-chometric standard and could be used to assess the intimate relationship well-being.

Objective:To study the distribution of drug resistance genes and virulence genes in multidrug-resistant Salmonella typhimurium strains.Methods:A total of 96 strains of Salmonella typhimurium were collected，and drug sensitivity tests were performed to evaluate the drug resistance and multidrug-resistance of Salmonella typhimurium.Multidrug-resistant Salmonella typhimurium strains were selected to conducted whole genome sequencing，and the distribution of drug resistance genes and virulence genes in the strain were analyzed.Results:Salmonella typhimurium strains had the highest resistance rates to ampicillin and ampicillin/sulbactam，with 89.58% and 76.04%，respectively.Followed by trimethoprim/sulfamethoxazole，ceftriaxone，and aztreonam，with 47.92%，38.54% and 33.33%，respectively，and low resistance rates to ciprofloxacin and levofloxacin，with 8.33% and 4.17%，respectively.Ninety-six strains were all sensitive to carbapenem antibiotics and piperacillin/tazobactam.Fifty-seven strains（59.38%）of Salmonella typhimurium showed multidrug-resistance.Resistance genes were detected in all 57 multidrug-resistant Salmonella typhimurium strains,with higher carrier rates of 98.25%,77.19%,and 59.65% for aac(6')-Iaa,aadA22,and blaTEM-1B,respectively.The multidrug-resistant Salmonella typhimurium strains had the highest carrier rates for invA，sipA，sseL，and sopB.Conclusion:Multidrug-resistant Salmonella typhimurium strains have a high incidence and a high carrier rate for multiple drug resistance genes and virulence genes.The monitoring and prevention of Salmonella typhimurium should be strengthened in the clinic in order to reduce the spreading epidemic of multidrug-resistant strains.

Objective:To design a motor impairment rehabilitation monitoring aid for the assessment of motor impairment in patients who do not have or have difficulty walking independently.Methods:An assistive device vehicle was designed, equipped with an accelerometer and a six-dimensional force sensor. The normal walking (NW) group and abnormal walking group were set up, in which the abnormal walking group included moderate abnormal walking (MA) group, moderate abnormal walking with the aid of the assistive vehicle (MA-V) group, severe abnormal walking (SA) group, and severe abnormal walking with the aid of the assistive vehicle (SA-V) group. In the MA-V group, the range of knee movement was adjusted from 0 to 30°, and in the SA group, the knee joint was completely unbending. The gait cycles, peak and mean acceleration values of the right and left legs were evaluated by accelerometers, and changes in the upper limb forces were assessed by six-dimensional force transducers.Results:For the moderate impairment group, the difference in gait cycle between the MA and MA-V groups was not statistically significant ( P>0.05), and the gait cycle in the MA-V group was slightly greater than that in the MA group. For the severe injury group, the gait cycle of the SA-V group was lower than that of the SA group, and the difference was statistically significant ( P<0.01). For all abnormal groups, the mean and peak acceleration of the left leg were greater than that of the right leg, and the difference between the peak acceleration of the left leg and that of the right leg was statistically significant ( P<0.05). In the abnormal walking pattern, the mean (absolute) value of the left hand force was greater than that of the right hand, especially in the Z-axis. The standard deviations of the combined forces on the left side for the NW, MA-V, and SA-V groups were 2.759, 8.297, and 13.118 N, respectively. The SA-V group had the highest dispersion in the force scatter plot, while the NW group had a better concentration. Conclusions:An assistive vehicle equipped with an accelerometer and a six-dimensional force sensor was designed to help physicians in the assessment and rehabilitation of motor disorders.

Objective:To explore the mechanism of biliary fibrosis after end to end anastomosis of bile duct.Methods:12 Neijiang miniature pigs (6-8 months old, weight 30-40 kg) were divided into experimental group ( n=6) and control group ( n=6). The model of end to end anastomosis after transection of the common bile duct was established in experimental group. Control group was a sham operation group, and only T tube was placed. After 9 months, Masson staining, fluorescence quantitative PCR and immunohistochemistry were used to analyze the expressing changes of pro-fibrotic factor transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and epithelial-mesenchymal transition (EMT) markers, including cytokeratin-19 (CK19), E-cadherin (E-Cad) and fibroblast specific protein-1 (S100A4), α-smooth muscle actin (α-SMA) and collagen components Collagen I (COL-1), collagen III (COL-3) and fibronectin (FN) in the anastomotic bile duct tissues. Results:Masson staining showed that the submucosal collagen fibers increased significantly in the experimental group. Compared with the control group, the mRNA expression of TGF-β1 [(3.482±0.313) vs. (1.000±0.102), t=18.43, P<0.001], CTGF [(2.160±0.287) vs. (1.000±0.103), t=9.32, P<0.001] were increased, the difference was statistically significant. Compared with control group, the mRNA and protein expression of CK19 and E-Cad were decreased in the experimental group, while the mRNA and protein expression of S100A4 and α-SMA were increased in the experimental group (all P<0.01). Conclusion:It was feasible in the short term to perform an end-to-end anastomosis after transection of the common bile duct, but there was an obvious fibrosis in the anastomotic bile duct tissue at later time.

Objective: To clinically validate the feasibility and accuracy of cine images acquired through the multitasking method, with no electrocardiogram gating and free-breathing, in measuring left ventricular (LV) function indices by comparing them with those acquired through the balanced steady-state free precession (bSSFP) method, with multiple breath-holds and electrocardiogram gating. Materials and Methods: Forty-three healthy volunteers (female:male, 30:13; mean age, 23.1 ± 2.3 years) and 36 patients requiring an assessment of LV function for various clinical indications (female:male, 22:14; 57.8 ± 11.3 years) were enrolled in this prospective study. Each participant underwent cardiac magnetic resonance imaging (MRI) using the multiple breath-hold bSSFP method and free-breathing multitasking method. LV function parameters were measured for both MRI methods. Image quality was assessed through subjective image quality scores (1 to 5) and calculation of the contrast-to-noise ratio (CNR) between the myocardium and blood pool. Differences between the two MRI methods were analyzed using the Bland–Altman plot, paired t-test, or Wilcoxon signed-rank test, as appropriate. Results: LV ejection fraction (LVEF) was not significantly different between the two MRI methods (P = 0.222 in healthy volunteers and P = 0.343 in patients). LV end-diastolic mass was slightly overestimated with multitasking in both healthy volunteers (multitasking vs. bSSFP, 60.5 ± 10.7 g vs. 58.0 ± 10.4 g, respectively; P < 0.001) and patients (69.4 ± 18.1 g vs. 66.8 ± 18.0 g, respectively; P = 0.003). Acceptable and comparable image quality was achieved for both MRI methods (multitasking vs. bSSFP, 4.5 ± 0.7 vs. 4.6 ± 0.6, respectively; P = 0.203). The CNR between the myocardium and blood pool showed no significant differences between the two MRI methods (18.89 ± 6.65 vs. 18.19 ± 5.83, respectively; P = 0.480). Conclusion Multitasking-derived cine images obtained without electrocardiogram gating and breath-holding achieved similar image quality and accurate quantification of LVEF in healthy volunteers and patients.

Objective:To explore a fast and accurate method to diagnose children's pneumonia according to respiratory signals, so as to avoid the cancer induction caused by traditional X-ray examination.Methods:A Mach Zehnder optical fiber sensor was used to build a respiratory signals(RSPs) detection system, and the RSPs of the monitored children were extracted according to the vibration signal generated by the children's lung rales. Preprocessing methods such as the discrete cosine transform(DCT) were used to compress and denoise the RSPs. Multi-feature extraction of RSPs was conducted through signal processing methods such as the Hilbert transform and autoregressive (AR) model spectrum estimation. A support vector machine (SVM) classification model was constructed to classify the collected RSPs.Results:The accuracy rate of the proposed RSP classification of children with or without pneumonia was 94.41%, which was higher than the previous methods.Conclusions:The children's pneumonia diagnosis system based on an optical fiber sensor has a higher detection accuracy, and is expected to be widely used in clinical practice.