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.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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In the study of embryo development process, the morphological features at different stages are essential to evaluate developmental competence of the embryo, which can be used to optimize and improve the system for
Blastocyst ; Embryo Culture Techniques ; Embryonic Development ; Fertilization in Vitro

OBJECTIVE: To construct a HIV-1 gp120 transgenic mice (gp120 Tg) with vimentin (VIM) gene knockout. METHODS: Female HIV-1 gp120 Tg mice were mated to VIM heterozygote mice (F0). All the offspring mice were derived from these original founders so that both genotypes had the same mixed genetic background. The F1 mice were bred to generate of VIM, VIM, VIM/gp120 Tg and VIM/gp120 Tg mice. PCR was performed for genotyping of the mice, and the expressions of VIM and gp120 in the brain tissues were examined using immunoblotting. RESULTS: The results of PCR showed the presence of the target bands in VIM, VIM, VIM/gp120 Tg and VIM/gp120 Tg mice. In VIM/gp120 Tg mice, gp120 expression was detected throughout the brain regions while no VIM expression was detected. CONCLUSIONS We generated gp120 transgenic mouse models with VIM gene knockout, which facilitate the exploration of the role of VIM in gp120-induced neurotoxicity.
Animals ; Brain ; Disease Models, Animal ; Female ; HIV Envelope Protein gp120 ; HIV-1 ; Mice ; Mice, Knockout ; Mice, Transgenic ; Vimentin

Objective: To investigate the role of HIV-1 envelope protein gp120 in cognitive impairment induced by neuronal damage. Methods: Western blot and immunofluorescence assay were used to detect microglia activation, inflammatory factor expression and neuronal damage after gp120 treatment. Neuronal damage and neurocognitive performance in gp120-transgenic mice were evaluated using immunohistochemical staining and behavioral analysis, respectively. Results: In vivo and in vitro experiments showed that HIV-1 gp120 significantly induced the expression of caspase-1 and IL-1β, and indirectly caused neuronal synaptic shortening and neuronal damage (P<0.05). Compared with wild-type mice, gp120-transgenic mice showed significant cortical and hippocampal glial activation, neuronal loss, dendritic damage and neurocognitive disorders. Conclusions HIV-1 gp120 might cause neuronal damage through activating the release of inflammatory factor by microglia and involve in neurocognitive impairment.

Objective: To investigate the hemostasis effect of hemocoagulase for injection in scalp incision in craniocerebral surgery, and evaluate its effect on coagulation function and drug safety. Methods: Before undergoing craniotomy, 60 patients were randomly divid-ed into the study group and the control group. The study group was injected with hemocoagulase for injection at 1u im at the night before surgery, 1u im 1h before incision and 1u im 15min before incision. The control group was injected with 0. 9% saline at the same time with the same volume. The hemorrhagic volume, hemorrhagic volume per square decimeter, hemostatic time, blood coagulation and ad-verse events were tested and compared between the groups. Results: In the study group, the mean hemorrhagic volume was (37. 18 ± 2. 96)g, the mean hemorrhagic volume per square decimeter was (0. 23 ± 0. 16)g·cm-2and the mean hemostatic time was (125. 53 ± 36. 42)s. In the control group, the corresponding value was (60. 69 ± 2. 30) g, (0. 42 ± 0. 25) g·cm-2and (182. 72 ± 52. 29) s, re-spectively. The hemorrhagic volume, hemorrhagic volume per square decimeter and hemostatic time significantly decreased in the study group when compared with those in the control group (P<0. 05). No significant difference in blood coagulation and safety (P>0. 05). No adverse event was reported. Conclusion: Hemocoagulase for injection shows promising hemostasis effect with high safety, which can ensure craniocerebral surgery going well with shortened operation time.

Hypothalamic neuronal hamartomas are rarely congenital developmental neuronal masses.They often attach to the third ventricle floor,mammillary bodies and tuber cinereum,and they are composed ofheterotopic gray matter,neurons,glia and myelinated fibers.This article summarizes the etiologies,pathologies,clinical manifestations and classifications,imaging features and therapy methods ofhypothalamic neuronal hamartomas.

Objective To analyze the related factors of foot blisters caused by long-distance weight-bearing march and to explore the pathogenesis of foot blisters to provide a useful way for the prevention and treatment.Methods After the 300 km march,counted the number who had accomplished the march,and then recorded the number of foot blisters,location of blisters,and abrasion of sole.Collected the data of gender,age,body mass index (BMI),hand dominance,and whether had bliters before the march through questionnaire.And the data were coded for analysis with SPSS 13.0 statistical package.Results The 7 cases who complete the whole march and 17 cases who already had foot blisters before the march were ruled out of the final statistics.Among the remaining 590 cases,there were 554 cases (93.9%)suffered from foot blisters.And there were 1 282 blisters in total,among which the plantar blisters occupied 98% (1 257 cases).The analysis showed that the incidence of foot blisters had no significant correlation with gender,left/right foot,hand dominance,BMI and age.The predilection sites of blisters were the second and third metatarsals (28.2%),the hallux (21.3%),the fifth metatarsal (18.1%),and the calcaneus (15.8%)of the left foot.The predilection sites of blisters were the second and third metatarsals (33.3%),the hallux (22.4%),the fifth metatarsal (18.6%),and the calcaneus (14.5%)of the right foot.In terms of the abrasion of sole,the lateral heel was worn out the most (34.6% on the left and 34.2% on the right).Conclusion The study confirmed that the incidence of foot blisters had no significant correla-tion with gender,left/right foot,hand dominance,BMI and age,which may be affected by the particularity of this march.Most of the foot blisters occurred in the planta,and the predilection sites of blisters were in accord with sites of of the abrasion of sole and the distribution of plantar shear force,which demonstrated the shear force is the most critical factor on the pathogenesis of foot blisters.