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.

Diabetes mellitus（DM） is a globally prevalent chronic metabolic disease， and its hyperglycemia can lead to a series of serious complications. Although current DM treatments are effective， they still have side effects and limitations. Therefore， discovering new drugs has become a key approach to improving DM management. As a traditional Chinese medicine， Dendrobii Caulis has garnered significant attention due to its rich phytochemical properties， which may offer a natural approach to mitigate the harmful effects of DM. Studies have demonstrated that Dendrobii Caulis can significantly reduce blood glucose levels in diabetic animal models and improve insulin resistance. Modern pharmacological studies have shown that the hypoglycemic effect of Dendrobii Caulis is primarily based on multiple mechanisms， including improving insulin sensitivity， inhibiting liver glycogen breakdown， promoting liver glycogen synthesis， and reducing oxidative stress. In addition， polysaccharides in Dendrobii Caulis have been found to increase the serum level of glucagon-like peptide-1 （GLP-1）， which promotes insulin secretion and inhibits glucagon release， thereby improving the symptoms of DM and its complications. Given its potential hypoglycemic effect， Dendrobii Caulis is expected to be developed as a new hypoglycemic agent or health food with promising prospects for treating DM and its complications. With further basic and clinical research， Dendrobii Caulis is expected to become an important adjunct in DM treatment.

ObjectiveTo investigate the possible mechanism of Wenyang Shengji Ointment （温阳生肌膏， WSO） in the treatment of diabetic wounds with yin syndrome. MethodsA total of 24 SD rats were randomly divided into a group （n=6） and modeling group （n=18）. The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection， full-thickness skin defects were created on the back of the rats to establish a diabetic wound with yin syndrome model. The normal group was fed with regular diet， and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups， the model group， the WSO group， and the Beifuxin （Recombinant Bovine Basic Fibroblast Growth Factor Gel， BX） group， 6 rats in each group. The WSO group was given the ointment to the wound， the Beifuxin group was givne BX gel， and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily for 14 days. Wound healing was recorded on days 0， 3， 7， and 14， and the wound healing rate was calculated on day 3， 7， and 14. On day 14 after treatment， HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha （HIF-1α） and vascular endothelial growth factor （VEGF）. Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue， and ELISA was used to detect the methylglyoxal （MGO） content in the wound tissue. ResultsCompared with the normal group， the model group showed poor wound healing on day 3， 7， and 14， with a low wound healing rate （P＜0.01）. HE staining showed scab coverage on the wound， with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced， while the relative protein levels of HIF-1α and the MGO content significantly increased （P＜0.01）， and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group， the WSO group and Beifuxin group showed better wound healing on day 3， 7， and 14， with an increased wound healing rate （P＜0.01）. The wound tissue showed clear and complete epithelial structure， reduced inflammatory cells， mature granulation tissue， and organized collagen arrangement. MGO content was significantly reduced （P＜0.01）. The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group， while only VEGF increased in the Beifuxin group （P＜0.05 or P＜0.01）. Compared with the Beifuxin group， the WSO group had a thicker epidermal layer， prominent collagen formation， significantly increased HIF-1α fluorescence expression， reduced MGO content in the wound tissue， and higher relative protein levels of HIF-1α （P＜0.05）. ConclusionWSO can reduce the accumulation of MGO in diabetic wound tissue with yin syndrome and activate the HIF-1α/VEGF pathway， which could be one of the mechanisms for promoting wound healing.

Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.

Super-pulse thulium fiber laser (hereinafter referred to as thulium laser) has shown broad application prospects in medical research, especially in the treatment of urinary tract stones.Thulium laser has a thin fiber diameter, which reduces the occupation of the working channel and increases the irrigation water flow.Currently, the peak power reaches up to 500 W, the single pulse energy to 6 J, and the frequency to 2000 Hz.The stone-breaking mechanism of thulium laser is photothermal and photomechanical.Different combinations of energy and frequency will significantly affect the volume of stone fragments. "High energy and low frequency" is more suitable for "fragmentation" stone breaking, while "low energy and high frequency" is more suitable for "powderization" stone breaking.Some in vitro experiments have confirmed that thulium laser has higher stone-breaking efficiency, less stone displacement, and more obvious thermal effects compared to holmium laser.Clinically, thulium laser has been applied to ureteroscopic lithotripsy and percutaneous nephrolithotomy., and the stone free rate and safety are relatively high.This article reviews the stone-breaking principles, in vitro experiments, and clinical applications of thulium laser, aiming to provide better theoretical support and practical experience for the development and application of super-pulse thulium fiber laser in the future.

ObjectiveTo investigate the regulatory effect of icariin （ICA） on transforming growth factor-β₁ （TGF-β₁）/Smad pathway in bone microvascular endothelial cells （BMECs） and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured， and the cell types were identified by immunofluorescence. Cells were divided into the control group， model group （0.1 g·L^-1 methyl prednisolone）， ICA group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA）， and TGF-β inhibitor group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA +1×10^-5 mol·L^-1 LY2157299）. Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β₁/ Smad pathway. ResultsAfter cell separation culture， platelet endothelial cell adhesion molecule （CD31） and von willebrand factor （vWF） immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged， and the nucleus was pyknotic and broken in the model group. Compared with the model group， the ICA group had complete cell membranes， clear structures， with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes， and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group， in the model group and the LY2157299 group， autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group， the mRNA and protein expressions of autophagy effector protein 1 （Beclin1） and microtubule-associated protein 1 light chain 3B （LC3B） in the model group were significantly decreased （P<0.01）， and those of ubiquitin-binding protein （p62） were significantly increased （P<0.01）. The mRNA expression of TGF-β₁， Smad homolog 2 （Smad2）， and Smad homolog 3 （Smad3） decreased （P<0.05， P<0.01）. The protein expressions of TGF-β₁， p-Smad2， and p-Smad3 were significantly decreased （P<0.01）. Compared with those of the model group， the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased （P<0.01）， and those of p62 significantly reduced （P<0.01）. The mRNA expression of TGF-β₁， Smad2， and Smad3 increased significantly （P<0.01）. The protein expression of TGF-β₁， p-Smad2， and p-Smad3 increased significantly （P<0.01）. Compared with those in the model group， the mRNA and protein expressions of Beclin1， LC3B， and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β₁ pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs， and its mechanism may be related to activating the TGF-β₁/Smad signaling pathway.

Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

BACKGROUND:Scholars at home and abroad consider New Zealand rabbits to be an ideal model animal because of the similar anatomical morphology of the lumbar spine to that of the human lumbar spine.There is a lack of systematic comparison of different ways to establish rabbit intervertebral disc degeneration models under X-ray guidance. OBJECTIVE:To establish a rabbit model of lumbar disc degeneration using X-ray guided acupuncture,end-plate injection and combined method,and to compare the modeling effects of these three methods. METHODS:Eighteen 6-month-old New Zealand white rabbits were randomly selected and divided into four groups:acupuncture group,endplate injection group,combined group and blank control group.In the acupuncture group,three consecutive segments of the intervertebral discs(L2/3,L3/4,L4/5)were needled and modeled;in the endplate injection group,50 μL of anhydrous ethanol was injected at a single point on the endplates of the three consecutive segmental discs;in the combined group,three consecutive segmental intervertebral discs were needled and injected with 50 μL of anhydrous ethanol at four azimuthal points on the endplates of the corresponding segmental discs;and the blank control group received no interventions.X-ray examination was performed to measure the disc height index at 2,4,and 8 weeks after surgery.The intervertebral disc tissues were then taken for anatomical observation and pathological examination. RESULTS AND CONCLUSION:(1)Anatomical examination showed that fibrous annulus rupture,nucleus pulposus degeneration,and total disc structure disorder were the main manifestation in the acupuncture group,endplate injection group,and combined group,respectively.(2)X-ray examination showed that the disc height index showed the most obvious reduction in the acupuncture group at 2 weeks after operation,significant reductions in the endplate injection group at 2 and 4 weeks after operation,and significant reductions in the combined group at 2,4,and 8 weeks after operation.(3)Pathological examination showed that the fibrous ring structure was damaged and the inner annulus fibrosus protruded inward in the acupuncture group;endplate fissure,disordered arrangement and nucleus loss were observed in the endplate injection group;total disc structure disorder with the nucleus pulposus losing water and shrinking and no obvious border with the broken annulus fibrosus was found in the combined group.To conclude,acupuncture,endplate injection and the modified endplate injection method can establish the rabbit intervertebral disc degeneration model.Compared with the single method,the modified endplate injection method can greatly accelerate and aggravate the degeneration of the intervertebral disc,and can effectively shorten the experiment period.

Objective: To examine the impacts of chemotherapy/radiotherapy, targeted therapy, and combined treatment on the quality of life in patients with intermediate and advanced lung cancer. Methods: The patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy, targeted therapy, and combined treatment for the first time were recruited from a tertiary hospital in Weifang City, Shandong Province, using a quota sampling method in September 2023. Basic information was collected using a general information questionnaire, and the quality of life was assessed using the Chinese version of Functional Assessment of Cancer Therapy-General. The investigation started on the 7th day of treatment, and the follow-ups were conducted at 3 and 6 months. The quality of life in patients with different treatment regimens and at different treatment time were compared using repeated measure analysis of variance. Results: There were 26 chemotherapy/radiotherapy patients, 32 targeted therapy patients, and 95 combination therapy patients. There were no significant differences in age, gender, place of residence, education level, self-rated economic status, medical insurance, pathological type and disease stage among the three treatment regimens (all P>0.05). The repeated measure analysis of variance showed an interaction effect between time and group among patients receiving the three treatment regimens (P<0.05). The quality of life scores of patients receiving combination therapy decreased with extended treatment time (all P<0.05). The quality of life scores of patients receiving targeted therapy at 3 and 6 months were lower than those treated for 7 days (both P<0.05). No significant differences were observed in quality of life scores among chemotherapy/radiotherapy patients with different treatment durations (all P>0.05). At 3 and 6 months, patients receiving combination therapy had lower quality of life scores compared to those receiving chemotherapy/radiotherapy or targeted therapy (all P<0.05). Conclusion The decline in quality of life for patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy and targeted therapy is less than that for patients receiving combined therapy.