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 summarize the clinical and imaging characteristics of Rosai-Dorfman disease (RDD) in order to improve the diagnosis of the disease.Methods The clinical and imaging features of 10 patients with RDD proved by pathology were retrospectively analyzed and the related literatures were reviewed.Results Ten patients including 7 males and 3 females,aged 8 to 54 years old,with average of 32 years old.White blood cells (BCA) and erythrocyte sedimentation rate (ESR) in 8 cases were normal.Eight cases manifested as painless enlarged lymph node or mass,of which 4 cases were accompanied with multisystem involvement.Three lesions involved lymph nodes,5 lesions were located in extranodal sites,while 2 lesions involved both lymph node and extranodal sites.RDD occurred in lymph nodes (n=3) manifested as multiple enlarged lymph nodes on CT imaging,showing mild or moderate the enhancement,or a heterogeneous ring-enhancement.Of 5 extranodal RDD lesions,3 cases underwent MR exmination.2 lesions manifested as subcutaneous soft tissue mass on left shoulder and anterior abdominal wall,1 lesion manifested as intracranial mass accompany with localised cranial bone destruction.Lesions in all 3 cases had poor margins and showed scatted areas of high signal on diffusion weighted images.Lesions exhibited remarkable heterogeneous enhancement on Gd-DTPA enhanced MR imaging,dural/fascia tail sign and dilated blood vessels could be found around the lesions.Intrahepatic RDD lesion showed fast washing out phenomenon on CT enhanced imaging.In 2 cases involved both lymph node and extranodal sites,1 case manifested as swelling pharyngeal lymph chain and nasopharynx,enlargement of lymph nodes in bilateral submandibular and cervical region abdominal cavity on CT imaging,the enhancement is mild and moderate,accompany with osteolytic lesions in right proximal humerus on X-ray.For the other case,CT images manifested as bilateral neck lymphadenopathy,accompanied with soft tissue mass in nasal cavity,the lesion showed mild/moderate enhancement.Conclusions RDD mostly appears in young and middle-aged men,and is rarely preoperatively diagnosed.RDD mainly manifests as painless enlarged lymph node or mass.RDD has a broad spectrum of radiographic appearance,varied according to different location of lesion.Scatted higher signal areas on diffusion weighted images in the masses and significantly heterogeneity enhancement with dilated blood vessels around the lesion could be helpful in diagnosing of extranodal RDD.

This study aimed to analyze the effect of the external method of tonifying kidney and promoting blood circulation on endometrial morphology of rats with kidney deficiency and blood stasis model. A total of 50 normal healthy unmated female SD rats of proestrus were selected with vaginal smear. Rats were randomly divided into the blank group, model group, high dose group and low dose group with the prescription of tonifying kidney and promoting blood circulation and theWu-Zi (WZ) group. Except the blank group, intragastric administration of hydroxyurea was given to other group to establish the kidney deficiency model. Meanwhile, clyster of distilled water was given to the blank group and the model group. And clyster of high dose and low dose prescription of tonifying kidney and promoting blood circulation was given to the high dose and low dose group, respectively. The intragastric administrations ofWu-Zi Yan-Zong(WZYZ) pills were given to theWu-Zi (WZ) group. On the 4th day of pregnancy, 10% of the macromolecule dextran was quickly injected to the caudal vein to induce blood stasis model 1 hour after the last medication administration. The uterus tissue section was observed by HE dyeing. The results showed that the thickness of covering epithelium of endometrium in the model group was lower than the blank group (P < 0.05). There were significant differences on the thickness of covering epithelium of endometrium in the high dose group and low dose group with the prescription of tonifying kidney and promoting blood circulation, the WZ group and the model group (P < 0.01). The sum of gland number and gland area as well as the maximum diameter / minimum diameter of the model group was significantly lower than that of the blank group (P< 0.05, orP < 0.01). The shape factor was the closest to “1”, which had significant difference compared with the blank group (P < 0.01). Compared with the model group, the sum of gland number and glandular lumen of the high dose and low dose group were increased at different levels (P < 0.05, orP < 0.01). The sum of gland number, glandular lumen area, shape factor, and maximum diameter / minimum diameter of WZ group had significant difference compared with the model group (P < 0.05, orP < 0.01). The sum of interstitial cells’ nucleus area, integral optical density of interstitial cells’ nucleus and number of interstitial blood vessels in the high dose and low dose group were significantly higher compared to the model group (P < 0.05, orP < 0.01). The sum of interstitial cells’ nucleus area and the integral optical density of interstitial cells’ nucleus in the WZ group were obviously higher than the model group (P < 0.01). It was concluded that the external method of tonifying kidney and promoting blood circulation can effectively improve the endometrial morphology of kidney-deficiency and blood-stasis rat model, promote the synchronous development of endometrial gland and stroma, in order to play a role to improve the endometrial receptivity.