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.

Hepatocellular carcinoma （HCC） with biliary duct tumor thrombus （BDTT） is currently not common in clinical practice and is easily misdiagnosed， and previously， it was often considered an advanced stage of the disease with a poor prognosis， making its treatment challenging. However， in-depth studies in recent years have gradually deepened our understanding of this disease， leading to significant changes in diagnostic and treatment concepts. Currently， comprehensive treatment， mainly surgery， is used for treatment， but there is still controversy over the selection of clinical treatment strategies. This article provides a detailed discussion on surgical methods and prognosis， in order to provide a reference for clinical treatment options.

ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P＜0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P＜0.05), with this increasing trend persisting in the third year (P＜0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P＜0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.

OBJECTIVE: To investigate the effectiveness of arthroscopic double fixation and enhanced suture of long head of biceps tendon (LHBT) in situ for repairing rotator cuff tear. METHODS: A retrospective analysis was conducted on 31 patients with rotator cuff tears and LHBT injuries admitted between June 2022 and November 2023. All patients underwent arthroscopic double fixation and enhanced suture of LHBT in situ. There were 12 males and 19 females, with an average age of 61.6 years (range, 53-76 years). There were 10 cases of acute injury and 21 cases of chronic injury. According to DeOrio and Cofield classification criteria, the degree of rotator cuff tear rated as medium-sized tears in 3 cases, large tears in 12 cases, and massive tears in 16 cases. Associated injuries included 5 cases of shoulder joint adhesions, 12 cases of subscapularis muscle tears, and 31 case of shoulder impingement syndromes. The shoulder range of motion (ROM) (forward flexion, abduction, lateral external rotation, lateral internal rotation) and pain/function scores [visual analogue scale (VAS) score, University of California Los Angeles (UCLA) shoulder score, Constant-Murley score] were recorded before operation and at last follow-up. MRI at last follow-up were taken to evaluate the rotator cuff healing and structural integrity. RESULTS: All 31 surgeries were successfully completed with operation time ranging from 90 to 210 minutes (mean, 144 minutes). The 3-5 anchors (mean, 3.8 anchors) were used during operation. All incisions healed by first intention. All patients were followed up 12-29 months (mean, 18.5 months). At 3 months after operation, 2 cases developed joint adhesions, 3 had internal rotation limitations, and 2 experienced residual pain at the intertubercular groove, all resolved with conservative management. No Popeye deformity occurred during follow-up. At last follow-up, shoulder ROM (forward flexion, abduction, lateral external rotation, lateral internal rotation) and pain/function scores (VAS, UCLA, and Constant-Murley scores) showed significant improvements compared to preoperative values ( P<0.05). At last follow-up, MRI evaluation showed that the rotator cuff healing rate reached 90.3% according to the Sugaya classification criteria. LHBT exhibited normal morphology, course, and continuity without dislocation. Surrounding synovial sheath showed no thickening or effusion. CONCLUSION Arthroscopic double fixation and enhanced suture of LHBT in situ for repairing rotator cuff tear can significantly reduce shoulder joint pain, improve ROM, and achieve a high rotator cuff healing rate.
Humans ; Male ; Middle Aged ; Arthroscopy/methods* ; Rotator Cuff Injuries/physiopathology* ; Female ; Retrospective Studies ; Aged ; Range of Motion, Articular ; Suture Techniques ; Treatment Outcome ; Rotator Cuff/surgery* ; Shoulder Joint/physiopathology* ; Tendons/surgery*

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity* ; Animals ; Gastric Mucosa/metabolism* ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Capsaicin/pharmacology* ; Male ; NADPH Oxidases/genetics* ; Mice ; Humans ; src-Family Kinases/genetics*

Objective To analyze the influencing factors of hepatic encephalopathy(HE)after transjugular intrahepatic portosystemic shunt(TIPS)and construct a nomogram prediction model based on these factors.Methods A total of 290 patients with cirrhotic portal hypertensive variceal gastrointestinal bleeding in the Yuncheng Central Hospital Affiliated to Shanxi Medical University from January 2019 to December 2023 were selected and randomly divided into training set of 145 cases and validation set of 145 cases.All patients underwent TIPS treatment,and the incidence of HE within 3 months after TIPS was recorded.In the training set,patients were divided into HE group(n=42)and non-HE group(n=103)based on the occurrence of HE.Clinical materials were compared between the two groups,and Lasso-Logistic regression analysis was applied to explore the influencing factors of HE after TIPS.A nomogram prediction model was constructed based on the influencing factors and validated in both the training set and the validation set for its clinical value in predicting HE after TIPS.Results The overall incidence of HE was 29.31％,with incidence rates of 28.97％and 29.66％respectively in the training set and the validation set.In the training set,the HE group had significantly higher age,C grading of preoperative Child-Pugh ratio,diabetes mellitus ratio,total bilirubin(TBIL),prothrombin time(PT),serum sodium,serum creatinine,interleukin-6(IL-6),interleukin-18(IL-18),blood ammonia,monocyte chemotactic protein-1(MCP-1),postoperative portal venous pressure,and intestinal flora disturbance ratio when compared to the non-HE group,while the preoperative glial fibrillary acidic protein(GFAP)level was significantly lower in the HE group(P＜0.05).Lasso-Logistic regression analysis showed that preoperative C grading of Child-Pugh grading,diabetes mellitus,TBIL,PT,IL-6,IL-18,blood ammonia,GFAP,MCP-1 level,and postoperative intestinal flora disturbance were influencing factors for HE after TIPS(P＜0.05).A nomogram prediction model was constructed based on ten influencing factors selected by Lasso-Logistic regression analysis.The area under the curve(AUC)of this model for predicting HE after TIPS was 0.933(95％CI,0.889 to 0.976)in the training set and 0.944(95％CI,0.893 to 0.995)in the valida-tion set,with good consistency between the model's prediction and actual observation.Conclusion The nomogram prediction model for HE after TIPS,constructed based on the influencing factors selected by Lasso-Logistic regression analysis,has high predictive efficacy and accuracy.

Objective This study aims to explore the complex relationship between social engagement and depressive symptoms among older adults in China,focusing particularly on the moderating role of marital status. Methods This study used data from the latest Chinese Longitudinal Healthy Longevity Survey(CLHLS).The analysis used the latent class analysis to delineate personality clusters and hierarchical linear regression,supplemented by the PROCESS macro,to investigate the effects of social engagement and marital status on depressive symptoms. Results The analysis encompassed 7,789 respondents(mean age:82.53[s=11.20]years),with 54%female.The personality analysis categorized participants into four clusters,with the majority(77.60%)classified as Confident Idealists,who exhibited the lowest levels of depressive symptoms.Hierarchical linear regression analysis yielded several significant findings:Higher levels of social engagement were significantly associated with fewer depressive symptoms(t=-7.932,P<0.001,B=-0.463).Marital status was a significant factor;married individuals reported fewer depressive symptoms compared to their unmarried counterparts(t=-6.368,P<0.001,B=-0.750).There was a significant moderating effect of marital status on the relationship between social engagement and depressive symptoms(t=-2.092,P=0.037,B=-0.217). Conclusion This study demonstrates that,among Chinese older adults,both social engagement and marital status significantly influence depressive symptoms.Higher social engagement,particularly in other activities like doing household chores,gardening,reading newspapers or books,and playing cards or Mahjong,is associated with fewer depressive symptoms,especially among married individuals.

Objective:To summarize the clinical features and postoperative efficacy of patients with oval window atresia accompanied by facial nerve aberration.Methods:The clinical data of patients with congenital middle ear malformation with facial nerve aberration admitted to our hospital from January 2015 to March 2023 were retrospectively analyzed. There were 97 cases (133 ears) in total. Among them, 39 patients (44 ears) had complete follow-up data, including 27 male patients and 12 females, aged 7-48 years old, with an average age of 17.8 years old. Of these, 14 cases (16 ears) were patients combined with facial nerve aberration, and 25 cases (28 ears) were without facial nerve aberration. The results of imaging examination, pure-tone audiometry, selection of surgical strategy, intraoperative findings and postoperative hearing improvement were summarized and analyzed. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Prism 9 software was used to statistically analyze the mean bone conductance and air-bone gap of patients before and after surgery.Results:All the 14 patients (16 ears) with middle ear malformation accompanied by facial nerve aberration and oval window atresia showed poor hearing and no facial palsy since childhood. High resolution CT (HRCT) examination of temporal bone, pure tone audiometry and Gelle test were performed before surgery. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Preoperative high-resolution CT (HRCT) examination of temporal bone found 12 ears with 4 or more deformities, accounting for 75.00%, in the group of patients with facial nerve malformation. The preoperative average bone conductive threshold was (15.3±10.4) dB and the average air-bone gap was (46.3±10.6) dB in pure-tone audiometry (0.5, 1, 2, 4kHz). According to the different degrees of facial nerve and ossicle malformation, we performed three different hearing reconstruction strategies for the 14 patients (16 ears) with facial nerve aberration and oval window atresia, including 7 ears of incus bypass artificial stape implantation, 7 ears of Malleostapedotomy (MS) and 2 ears of Malleus-cochlear-prothesis (MCP). After 3 months to 18 months of follow-up, all patients showed no facial paralysis. The postoperative mean bone conductive threshold was (15.7±7.9) dB and air-bone gap was (19.8±8.5) dB. There were significant differences in mean air-bone gap before and after operation ( t=7.766, P<0.05), and there was no significant difference between the mean bone conductive threshold before and after surgery ( t=0.225, P=0.824). There was no significant difference of mean reduction of air-bone gap between patients with and without facial nerve aberration ( t=1.412, P=0.165). There was no significant difference between the three hearing reconstruction strategies. There was no significant displacement of the Piston examined by U-HRCT. Conclusion:For patients of middle ear malformation whose facial nerve cover the oval window partially, incus bypass artificial stape implantation or Malleostapedotomy (MS) can be selected according to the specific condition of auditory ossis malformation, and for patients whose facial nerve completely covers the oval window area, Malleus-cochlear-prothesis (MCP) can be selected. Three types of stapes surgery are safe and reliable for patients with oval window atresia accompanied by facial nerve aberration. There was no significant difference in efficacy between them. Preoperative HRCT assessment of middle ear malformation is effective. There is no significant difference of surgical effect with or without facial nerve aberration. The U-HRCT can be used to evaluate the middle ear malformation before surgery and the Piston implantation status after surgery. Due to the risks of surgery, those who do not want to undergo surgery can choose artificial hearing AIDS, such as hearing aid, vibrating soundbridge, bone bridge or bone-anchored hearing aid.

BACKGROUND:Tissue engineering is considered an ideal treatment for growth plate regeneration.However,most of the current research on regenerative tissue engineering is the traditional scaffold-based strategy.As the limitations of traditional scaffolds are gradually revealed,the research direction is gradually diversifying. OBJECTIVE:To summarize the application of scaffold-based and scaffold-free strategies in the treatment of growth plate cartilage regeneration and their respective advantages and disadvantages. METHODS:The relevant articles were searched from PubMed,Wiley,and Elsevier.The search terms were"growth plate injury,regeneration,tissue engineering,scaffold,scaffold-free,biomimetic,cartilage"in English.The time was limited from 1990 to 2023.Finally,104 articles were included for review. RESULTS AND CONCLUSION:The biomimetic strategy is to reduce the cell composition,biological signals and unique mechanical properties of each region to the greatest extent by simulating the unique organizational structure of the growth plate,so as to build a biomimetic microenvironment that can promote tissue regeneration.Therefore,the design of a biomimetic scaffold is to simulate the original growth plate as far as possible in terms of composition,structure and mechanical properties.Although some results have been achieved,there is still the problem of the unstable regeneration effect.The scaffold-free strategy believes that the limitations of scaffolds will have adverse effects on regenerative therapy.Therefore,the design of scaffold-free constructs relies as much as possible on the ability of cells to generate and maintain extracellular matrix without interfering with cell-cell signals or introducing exogenous substances.However,there are some problems,such as poor stability,low mechanical strength and greater difficulty in operation.Biomimetic strategy and scaffold-free strategy have different emphases,advantages and disadvantages,but they both have positive effects on growth plate cartilage regeneration.Therefore,subsequent studies,whether adopting a biomimetic strategy or a scaffold-free strategy,will focus on the continuous optimization of existing technologies in order to achieve effective growth plate cartilage regeneration therapy.