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.

Modern Traditional Chinese Medicine(TCM)physicians believed that"reproduction depends on the kidney"theory is the key in treating fetal leakage,fetal restlessness,slippery fetus and other diseases.However,before the Ming and Qing Dynasties,ancient physicians paid special attention to the theory of"Qi and blood in the spleen and stomach".The"the stem of fetal ties the spleen"came from the summary of Zhao Xianke's"Handan manuscripts"based on analogy of nature in Ming dynasty.However,at present,the relevant research reports on"spleen"and tocolysis are fragmented,and the theoretical traceability,clinical effects and experimental research are not systematically discussed.Based on the"fetal stem ties the spleen"theory,through integrated research,taking the differentiation of ancient and modern theories of traditional Chinese medicine gynecology as the"longitude",and the progress of modern biological research on"syndromes,prescriptions and components"as the"latitude".This study is an initial attempt to reveal the key inflection points deductively in the empty space(territorial schools)during(history and history of)tocolysis,and to systematically explore the"spleen main Qi","spleen main transportation","spleen main rising Qing"and"spleen main muscle",which are associated with the progress of the objectification and the bottleneck of research on the treatment of tocolysis.Furthermore,it is proposed that TCM prescription syndrome metabolism and spatiotemporal omics are the important trends to solve the disputes and difficulties in the study of tocolysis in the future,and provide a new reference idea for the inheritance,innovation,breakthrough and accurate research of modern TCM reproductive theory.

ObjectiveTo explore difference in the mechanism of Shoutaiwan， a representative kidney-tonifying and abortion-preventing formula， and Juyuanjian， a typical spleen-invigorating and abortion-preventing formula in reversing the pathology of decidua of spontaneous abortion （SA） patients and to expound the connotation of "uterine collaterals connecting kidney" and "fetal collaterals connecting spleen" theory. MethodThe targets of SA were retrieved from GeneCards， followed by gene ontology-biological process （GO-BP） annotation. Based on Cytoscape and previous research， the main processes and core targets were screened out. High-performance liquid chromatography-mass spectrometry （HPLC-MS） was used to identify the potential active components of Shoutaiwan and Juyuanjian and the regulatory networks were constructed. SA was induced in rats and the model rats were treated with Shoutaiwan and Juyuanjian at the same unit. Hematoxylin and eosin （HE） staining， transmission electron microscopy （TEM）， enzyme-linked immunosorbent assay （ELISA）， immunohistochemistry （IHC）， immunofluorescence （IF）， and other methods were employed to verify the mechanisms against miscarriage. ResultThe dysregulation of cell adhesion， inflammatory response， cell death， and angiogenesis was the core pathological process of SA. A total of 13 potential specific active components of Shoutaiwan and 14 active components of Juyuanjian were screened out. The regulatory networks showed that the potential active components of the two prescriptions modulated vascular endothelial growth factor （VEGF）， interleukin （IL）-2， estrogen receptor （ESR）-1， matrix metalloproteinase-9 （MMP-9）， and other targets to regulate the pathological process of SA. The two can significantly improve the pregnancy rate and the integrity rate and blood supply of decidua cells， control the apoptosis morphology and the expression of estrogen （E₂）， progesterone （P）， and its receptor， and down-regulate the expression of MMP-2， MMP-9， IL-2， and IL-6 in decidua tissue of SA rats. At the same time， they up-regulated the expression of anti-apoptotic protein B-cell lymphoma-2 （Bcl-2） and IL-4. Shoutaiwan significantly up-regulated the expression of VEGF， and Juyuanjian significantly down-regulated the expression of E-cadherin （E-Cad）. ConclusionBoth Shoutaiwan and Juyuanjian regulate the core pathological process of SA to prevent miscarriage. At the same unit， Shoutaiwan is overall superior to Juyuanjian. Shoutaiwan is better than Juyuanjian in regulating angiogenesis and Juyuanjian is superior to Shoutaiwan in regulating cell adhesion. This conclusion can partly explain the biological basis of "treating the same disease with different methods"， and provide objective data reference for the identification of quality marker （Q-marker） of anti-miscarriage Chinese medicine and further study of formula-syndrome metabolome.

Objective:To investigate the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and blood platelet count (BPC) in judging the prognosis of adult patients with extensive burns.Methods:From January 2012 to December 2018, 99 adult patients with extensive burns who met the inclusion criteria were admitted to Union Hospital of Fujian Medical University, including 76 males and 23 females, aged 18 to 75 (43±13) years. According to the prognosis, the patients were divided into survival group of 79 cases and death group of 20 cases. Their clinical data were retrospectively analyzed by the method of case-control study. The gender, age, total burn area, inhalation injury, use of mechanical ventilation and white blood cell count, neutrophil count, lymphocyte count, and BPC on post injury day (PID) 1, 3, and 7 were collected, and the NLR, PLR, difference value of BPC on PID 3 and PID 1 (ΔBPC3), difference value of NLR on PID 3 and PID 1 (ΔNLR3), difference value of PLR on PID 3 and PID 1 (ΔPLR3), difference value of BPC on PID 7 and PID 1 (ΔBPC7), difference value of NLR on PID 7 and PID 1 (ΔNLR7), difference value of PLR on PID 7 and PID 1 (ΔPLR7) of patients in the two groups were calculated. Data were statistically analyzed with Mann-Whitney U test, independent sample t test, chi-square test to screen the death-related factors of patients. Binary classification single factor and multifactor logistic regression analysis were used to analyze the death-related factors of patients. The receiver′s operating characteristic (ROC) curve of the independent risk factor of death of patients predicting the prognosis of adult patients with extensive burns was drawn, and the area under the curve, the optimal threshold and its sensitivity and specificity were calculated. Results:(1) There were statistically significant differences in total burn area and use of mechanical ventilation of patients between the two groups ( Z=-2.615, χ2=7.282, P<0.01). (2) On PID 1, there was statistically significant difference in NLR of patients between the two groups ( Z=-2.414, P<0.05). On PID 3, there were statistically significant differences in BPC and ΔNLR3 of patients between the two groups ( Z=-2.048, -2.780, P<0.05 or P<0.01). On PID 7, there were statistically significant differences in lymphocyte count, BPC, NLR, and ΔNLR7 of patients between the two groups ( Z=-2.248, -2.231, -2.641, -3.669, P<0.05 or P<0.01). (3) Binary classification single factor logistic regression analysis showed that the total burn area, mechanical ventilation, BPC and NLR on PID 7, and ΔNLR7 were related to death of patients (odds ratio=1.038, 0.193, 0.990, 1.086, 1.105, 95% confidence interval=1.010-1.067, 0.062-0.598, 0.982-0.998, 1.012-1.165, 1.037-1.178, P<0.05 or P<0.01). Binary classification multifactor logistic regression analysis showed that ΔNLR7 was the independent risk factor of death of adult patients with extensive burns (odds ratio=1.090, 95% confidence interval=1.008-1.178, P<0.05). (4) The optimal threshold of ROC curve of ΔNLR7 for predicting the prognostic death of 97 adult patients with extensive burns was -0.073 4. The sensitivity under the optimal threshold was 65.0%, and the specificity was 78.5%. The area under the ROC curve was 0.776 (95% confidence interval=0.650-0.882, P<0.01). Conclusions:Dynamic monitoring of NLR and BPC is of great significance to assist in judging the prognosis of adult patients with extensive burns. ΔNLR7 is an independent predictor of death in adult patients with extensive burns, while PLR can not predict the death of adult patients with extensive burns.

Objective: To explore the clinical effects of artificial dermis combined with vacuum sealing drainage (VSD) and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn. Methods: A total of 8 patients with scar hyperplasia and contracture deformity on joint after healing of extensive burn were admitted to our hospital from August 2015 to August 2017. There were 5 females and 3 males aged 8 to 45 years with an average of 23 years. In the first stage operation, scar tissue on contracture site was removed, and the wound was covered by artificial dermis followed by continued VSD treatment. On 10-14 d after the first stage operation, the artificial dermis tissue formed, and the second stage autologous split-thickness skin grafting and continued VSD treatment were performed. Routine anti-scar therapy was carried out after healing of wounds. Time of wound healing after the second stage operation was recorded. Colour and texture of the split-thickness skin graft, scar formation condition of the donor site, and action condition of the operation site during follow-up were observed. Results: The wounds of 8 patients were healed in 10-14 d after the second stage operation. During follow-up of 6-24 months, the split-thickness skin graft was with smooth surface and good elasticity, and the function of joint recovered well. The donor site in head healed well with no scar. Only pigmentation was left in the donor site of thigh, and scar was not obvious. The patients and their family members were satisfied. Conclusions After application of artificial dermis combined with VSD and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn, the skin grafting area and donor site were with unobvious scar hyperplasia, and the joint function in the operation area was good.