1.Molecular Crosstalk Mechanisms of Shoutai Wan and Juyuan Jian on Maternal-fetal Interface Subcellular Clusters in CBA/J×DBA/2 Recurrent Pregnancy Loss Model
Jingxin GAO ; Qiuping CHEN ; Xiaoyan ZHENG ; Pengfei ZENG ; Rui ZHOU ; Yancai TANG ; Qian ZENG ; Wenli GUO ; Jinzhu HUANG ; Weijun DING ; Linwen DENG ; Hang ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):70-87
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.
2.Concept, design and clinical application of minimally invasive liver transplantation through laparoscopic combined upper midline incision
Shuhong YI ; Hui TANG ; Kaining ZENG ; Xiao FENG ; Binsheng FU ; Qing YANG ; Jia YAO ; Yang YANG ; Guihua CHEN
Organ Transplantation 2025;16(1):67-73
Objective To explore the technical process and clinical application of laparoscopic combined upper midline incision minimally invasive liver transplantation. Methods A retrospective analysis was conducted on 30 cases of laparoscopic combined upper midline incision minimally invasive liver transplantation. The cases were divided into cirrhosis group (15 cases) and liver failure group (15 cases) based on the primary disease. The surgical and postoperative conditions of the two groups were compared. Results All patients successfully underwent laparoscopic "clockwise" liver resection, with no cases of passive conversion to open surgery or intolerance to pneumoperitoneum. In 6 cases, the right lobe was relatively large, and the right hepatic ligaments could not be completely mobilized. One case required an additional reverse "L" incision during open surgery. All patients successfully completed the liver transplantation, with no major intraoperative bleeding, cardiovascular events, or other occurrences in the 30 patients. The model for end-stage liver disease (MELD) score in the cirrhosis group was lower than that in the liver failure group (P<0.001). There were no statistically significant differences between the two groups in terms of age, surgical time, blood loss, anhepatic phase, or cold ischemia time (all P>0.05). During the perioperative period, there was 1 case of hepatic artery embolism, 1 case of portal vein anastomotic stenosis, no complications of hepatic vein and inferior vena cava, and 3 cases of biliary anastomotic stenosis, all of which occurred in the liver failure group. Conclusions In strictly selected cases, the minimally invasive liver transplantation technique combining laparoscopic hepatectomy with upper midline incision for graft implantation has the advantages of smaller incisions, less bleeding, relatively easier operation, and faster postoperative recovery, which is worthy of clinical promotion and application.
3.Research progress of meibomian gland dysfunction-related dry eye
Jianbo ZHONG ; Guoqiang ZENG ; Yi ZHANG ; Xiaoyan DOU ; Wanmei TANG ; Kunling CHEN ; Li CAI
International Eye Science 2025;25(2):259-263
In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.
4.Mechanism of Pizhan Powder in regulating the Wnt4/β-catenin signaling pathway to promote wound healing in mice with chronic skin ulcers
Pingxinyi QUE ; Xiang XIAO ; Li ZENG ; Xianbin ZHAO ; Min XIAO ; Songqi TANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):205-215
Objective:
We aimed to explore the mechanism of Pizhan Powder in regulating the Wnt4/β-catenin signaling pathway to promote wound healing in mice with chronic skin ulcer.
Methods:
Male BALB/c mice were divided into blank, model, Pizhan Powder, Pizhan powder removed bark medications, bark medications, inhibitor, and Pizhan Powder + inhibitor groups using the random number table method, with six mice per group. Except for the blank group, chronic skin ulcer wound models were prepared in the other groups by implanting foreign bodies. The blank control group received no treatment, whereas the wounds of the model group were cleaned with furacilin solution. The Pizhan Powder, Pizhan Powder removed bark medications, and bark medications groups were each administered 0.1 g of the corresponding medication on the skin wounds. The inhibitor group received an intraperitoneal injection of 3-(4-methylphenylsulfonamido) benzoic acid methyl ester (MSAB) at a dosage of 10 mg/kg. The Pizhan Powder + inhibitor group was administered 0.1 g of Pizhan Powder on the skin wound, and an intraperitoneal injection of MSAB was also administered (10 mg/kg). These treatments were administered once a day for 14 consecutive days. Wound healing was observed on the first, third, seventh, and 14th day of treatment; hematoxylin and eosin staining was used to observe the pathological changes of ulcerated skin; keratin 10 (CK10), keratin 14 (CK14), cell proliferation nuclear antigen (Ki-67), α-smooth muscle actin (α-SMA), and β-catenin expression in wounds was observed through immunofluorescence; Western blotting was used to detect the expression of signaling pathway-related proteins (Wnt4 and β-catenin).
Results:
Compared to the model group, the Pizhan Powder group showed a reduced wound area and an increased wound healing rate (P<0.05) and elevated CK10, CK14, Ki-67, α-SMA, β-catenin, and Wnt4 protein expressions (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the bark medications and Pizhan Powder removed bark medications groups was reduced (P<0.05). The wound healing rate and the fluorescence expression of CK10, CK14, Ki-67, and α-SMA in the Pizhan Powder removed bark medications group were lower than that in the bark medications group (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the Pizhan Powder + inhibitor group was reduced, and CK10, CK14, Ki-67, α-SMA, β-catenin and Wnt4 protein expression were lower (P<0.05).
Conclusion
Pizhan Powder promotes wound healing in chronic skin ulcers of mice by regulating the Wnt4/β-catenin signaling pathway. The bark medications (buffalo hide, white mulberry root-bark, and Chinese wolfberry root-bark) play a crucial role, representing a concrete application of the traditional Chinese medicine theory of " treating skin with skin.
5.Progress on antisense oligonucleotide in the field of antibacterial therapy
Jia LI ; Xiao-lu HAN ; Shi-yu SONG ; Jin-tao LIN ; Zhi-qiang TANG ; Zeng-ming WANG ; Liang XU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2025;60(2):337-347
With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.
6.Analysis of abnormal ALT in blood donors in five Zang autonomous prefectures of Qinghai Province, China: characteristics and screening strategies
Yingnan DANG ; ; Rong TANG ; Liqin HUANG ; Hailin WU ; Tingting CHEN ; Shengju LI ; Yanli SUN ; Xin ZHENG ; Yanxia LI ; Xianlin YE ; Jinfeng ZENG
Chinese Journal of Blood Transfusion 2025;38(4):502-507
[Objective] To investigate the factors associated with alanine aminotransferase (ALT) abnormalities in multi-ethnic blood donors across five Zang autonomous prefectures in the plateau regions of Qinghai Province, and to provide evidence for ensuring blood safety and formulating screening strategies. [Methods] A retrospective analysis was performed on the ALT abnormal test results of blood donors in the Zang autonomous prefectures of Qinghai from 2022 to 2024. The correlations between ALT levels and factors including gender, age, altitude, and infectious markers were investigated. [Results] The overall ALT unqualified rate among blood donors in this region was 9.01%. Significant differences in ALT levels were observed across genders and age groups (P<0.05). Variations in ALT abnormality rates were also noted among different plateau regions (P<0.05). Overall, ALT values exhibited an increasing trend with rising altitude. The average ALT unqualified rates were 11.19% in Zang donors, 7.96% in Han donors, and 4.79% in donors from other ethnic groups (P<0.05). No statistically significant association was observed between ALT abnormality and the presence of HBV/HCV infectious markers (P>0.05). [Conclusion] In the plateau areas of Qinghai, multi-ethnic blood donors have a relatively high ALT levels and ALT unqualified rates, showing distinct regional characteristics. ALT elevation in voluntary blood donors is related to non-pathological factors such as gender, age, and dietary habits, but not to infectious indicators.
7.Introduction and enlightenment of the Recommendations and Expert Consensus for Plasm a and Platelet Transfusion Practice in Critically ill Children: from the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB)
Lu LU ; Jiaohui ZENG ; Hao TANG ; Lan GU ; Junhua ZHANG ; Zhi LIN ; Dan WANG ; Mingyi ZHAO ; Minghua YANG ; Rong HUANG ; Rong GUI
Chinese Journal of Blood Transfusion 2025;38(4):585-594
To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.
8.Application of middle hepatic vein splitting and reconstruction technique in split liver transplantation from low-age donor livers
Hui TANG ; Binsheng FU ; Qing YANG ; Jia YAO ; Kaining ZENG ; Xiao FENG ; Shuhong YI ; Yang YANG
Organ Transplantation 2025;16(3):453-459
Objective To explore the feasibility and clinical experience of the middle hepatic vein splitting-reconstruction technique in split liver transplantation from low-age donor livers. Methods A retrospective analysis was conducted on the cases of two low-age donor livers that underwent middle hepatic vein splitting-reconstruction, which were transplanted into four child recipients at the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to July 2023. The surgical and postoperative conditions were summarized and analyzed. Results Donor 1 was a 6-year-old and 4-month-old girl with a body weight of 21 kg, and the obtained donor liver weighed 496 g. After splitting, the left and right liver weights were 201 g and 280 g, and transplanted into a 9-month-old boy weighing 6.5 kg and a 9-month-old boy weighing 7.5 kg, respectively. The graft to recipient weight ratio (GRWR) was 3.09% and 3.73%, respectively. Donor 2 was a 5-year-old and 8-month-old boy with a body weight of 19 kg, and the donor liver weighed 673 g. After splitting, the left and right liver weights were 230 g and 400 g, and transplanted into a 13-month-old girl weighing 9.5 kg and a 15-month-old boy weighing 12 kg. The GRWR was 2.42% and 3.33%, respectively. Both donor livers were split ex vivo, with the middle hepatic vein being completely split in the middle and reconstructed using allogeneic iliac vein and iliac artery vascular patches. According to GRWR, none of the 4 transplant livers were reduced in volume. Among the 4 recipients, one died due to postoperative portal vein thrombosis and non-function of the transplant liver, while the other three cases recovered smoothly without early or late complications. Regular follow-up was conducted until July 31, 2023, and liver function recovered well. Conclusions Under the premise of detailed assessment of the donor liver and meticulous intraoperative operation, as well as matching with suitable child recipients, low-age donor livers may be selected for splitting. The complete splitting and reconstruction of the middle hepatic vein in the middle may effectively ensure the adequate venous return of the left and right liver and provide sufficient functional liver volume.
9.Analysis of syncopal DRVR in blood donors: multicenter hemovigilance data (2020—2023)
Junhong YANG ; Qing XU ; Wenqin ZHU ; Fei TANG ; Ruru HE ; Zhenping LU ; Zhujiang YE ; Fade ZHONG ; Gang WU ; Guoqiang FENG ; Xiaojie GUO ; Jia ZENG ; Xia HUANG
Chinese Journal of Blood Transfusion 2025;38(8):1071-1076
Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.
10.Oxidative Stress-related Signaling Pathways and Antioxidant Therapy in Alzheimer’s Disease
Li TANG ; Yun-Long SHEN ; De-Jian PENG ; Tian-Lu RAN ; Zi-Heng PAN ; Xin-Yi ZENG ; Hui LIU
Progress in Biochemistry and Biophysics 2025;52(10):2486-2498
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.


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