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.

BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis＜10°),compensated group(10°＜pelvic incidence-lumbar lordosis＜20°),and decompensated group(pelvic incidence-lumbar lordosis＞20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P＜0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P＜0.01),and decreases in hip-knee-angle,and knee flexion angle(P＜0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P＜0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P＜0.05)and a significant increase in pelvic incidence-lumbar lordosis(P＜0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P＜0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis＜10°),compensated group(10°＜pelvic incidence-lumbar lordosis＜20°),and decompensated group(pelvic incidence-lumbar lordosis＞20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P＜0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P＜0.01),and decreases in hip-knee-angle,and knee flexion angle(P＜0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P＜0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P＜0.05)and a significant increase in pelvic incidence-lumbar lordosis(P＜0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P＜0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective To analyze the difference of psoas major muscle morphology and pain degree in patients with different types of lumbar disc herniation ( LDH ) by quantitative CT, and to further explore the relationship between psoas major muscle morphology and pain degree. Methods A total of 120 patients with LDH admitted to our hospital from January to December 2025 were enrolled as study subjects. Based on clinical symptoms and lesion location, they were divided into a simple lower extremity pain group and a lumbar and leg pain group. All patients underwent lumbar CT examination. The psoas major muscle index was used as a CT quantitative parameter, which was calculated as the mean of the maximum cross-sectional areas of both psoas major muscles divided by the cross-sectional area of the L5 vertebral body. This index was measured to reflect psoas major muscle morphology. Pain severity was assessed using the visual analogue scale (VAS). Differences in psoas major muscle morphology and pain severity between the two groups were compared. A Pearson correlation analysis was used to examine the relationship between the psoas major muscle index and pain severity. A linear regression model was used to analyze the independent risk factors affecting pain severity. Results There were no statistically significant differences in sex, age, or body mass index between the two groups (P>0.05). The disease duration was longer and the incidence of anxiety and depression was higher in the lumbar and leg pain group than those in the simple lower extremity pain group (P<0.05). Compared with the simple lower extremity pain group, the lumbar and leg pain group showed lower psoas major muscle index [(0.53 ± 0.05) vs. (0.61 ± 0.07)] and higher VAS score [(4.67 ± 1.10) vs. (3.02 ± 0.89)], and the differences were statistically significant (P<0.05). Pearson correlation analysis revealed a negative correlation between the psoas major muscle index and the VAS score (r=−0.288, P<0.05). Linear regression model analysis indicated that the independent risk factors affecting the VAS score were age, disease duration, LDH type, and the psoas major muscle index. Conclusion Compared with LDH patients with simple lower extremity pain, those with lumbar and leg pain demonstrate a longer disease duration, a higher incidence of anxiety and depression, and a higher severity of psoas major muscle atrophy and pain. The severity of pain is associated with not only advanced age and prolonged disease duration but also the LDH type and psoas major muscle atrophy.

Objective To analyze the difference of psoas major muscle morphology and pain degree in patients with different types of lumbar disc herniation ( LDH ) by quantitative CT, and to further explore the relationship between psoas major muscle morphology and pain degree. Methods A total of 120 patients with LDH admitted to our hospital from January to December 2025 were enrolled as study subjects. Based on clinical symptoms and lesion location, they were divided into a simple lower extremity pain group and a lumbar and leg pain group. All patients underwent lumbar CT examination. The psoas major muscle index was used as a CT quantitative parameter, which was calculated as the mean of the maximum cross-sectional areas of both psoas major muscles divided by the cross-sectional area of the L5 vertebral body. This index was measured to reflect psoas major muscle morphology. Pain severity was assessed using the visual analogue scale (VAS). Differences in psoas major muscle morphology and pain severity between the two groups were compared. A Pearson correlation analysis was used to examine the relationship between the psoas major muscle index and pain severity. A linear regression model was used to analyze the independent risk factors affecting pain severity. Results There were no statistically significant differences in sex, age, or body mass index between the two groups (P>0.05). The disease duration was longer and the incidence of anxiety and depression was higher in the lumbar and leg pain group than those in the simple lower extremity pain group (P<0.05). Compared with the simple lower extremity pain group, the lumbar and leg pain group showed lower psoas major muscle index [(0.53 ± 0.05) vs. (0.61 ± 0.07)] and higher VAS score [(4.67 ± 1.10) vs. (3.02 ± 0.89)], and the differences were statistically significant (P<0.05). Pearson correlation analysis revealed a negative correlation between the psoas major muscle index and the VAS score (r=−0.288, P<0.05). Linear regression model analysis indicated that the independent risk factors affecting the VAS score were age, disease duration, LDH type, and the psoas major muscle index. Conclusion Compared with LDH patients with simple lower extremity pain, those with lumbar and leg pain demonstrate a longer disease duration, a higher incidence of anxiety and depression, and a higher severity of psoas major muscle atrophy and pain. The severity of pain is associated with not only advanced age and prolonged disease duration but also the LDH type and psoas major muscle atrophy.

Objective To analyze the difference of psoas major muscle morphology and pain degree in patients with different types of lumbar disc herniation ( LDH ) by quantitative CT, and to further explore the relationship between psoas major muscle morphology and pain degree. Methods A total of 120 patients with LDH admitted to our hospital from January to December 2025 were enrolled as study subjects. Based on clinical symptoms and lesion location, they were divided into a simple lower extremity pain group and a lumbar and leg pain group. All patients underwent lumbar CT examination. The psoas major muscle index was used as a CT quantitative parameter, which was calculated as the mean of the maximum cross-sectional areas of both psoas major muscles divided by the cross-sectional area of the L5 vertebral body. This index was measured to reflect psoas major muscle morphology. Pain severity was assessed using the visual analogue scale (VAS). Differences in psoas major muscle morphology and pain severity between the two groups were compared. A Pearson correlation analysis was used to examine the relationship between the psoas major muscle index and pain severity. A linear regression model was used to analyze the independent risk factors affecting pain severity. Results There were no statistically significant differences in sex, age, or body mass index between the two groups (P>0.05). The disease duration was longer and the incidence of anxiety and depression was higher in the lumbar and leg pain group than those in the simple lower extremity pain group (P<0.05). Compared with the simple lower extremity pain group, the lumbar and leg pain group showed lower psoas major muscle index [(0.53 ± 0.05) vs. (0.61 ± 0.07)] and higher VAS score [(4.67 ± 1.10) vs. (3.02 ± 0.89)], and the differences were statistically significant (P<0.05). Pearson correlation analysis revealed a negative correlation between the psoas major muscle index and the VAS score (r=−0.288, P<0.05). Linear regression model analysis indicated that the independent risk factors affecting the VAS score were age, disease duration, LDH type, and the psoas major muscle index. Conclusion Compared with LDH patients with simple lower extremity pain, those with lumbar and leg pain demonstrate a longer disease duration, a higher incidence of anxiety and depression, and a higher severity of psoas major muscle atrophy and pain. The severity of pain is associated with not only advanced age and prolonged disease duration but also the LDH type and psoas major muscle atrophy.

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 evaluate the clinical efficacy and prognosis of mechanical lithotripsy, laser lithotripsy under direct peroral cholangioscopy, and their combination in the treatment of difficult common bile duct (CBD) stones.Methods:Clinical data of 345 patients with difficult CBD stones treated at the Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, between January 2020 and December 2024 were retrospectively analyzed, including 176 males and 169 females, aged (71.2±14.2) years. Patients were categorized into three groups based on the lithotripsy technique used: mechanical lithotripsy group ( n=275), laser lithotripsy group under direct peroral cholangioscopy ( n=34), and combined lithotripsy group ( n=35). Operative time, hospitalization costs, stone clearance rate, and postoperative complications were recorded. Follow-ups were conducted through outpatient visits and telephone reviews to monitor stone recurrence. Propensity score matching (PSM) at a 1: 3 nearest-neighbor ratio with a caliper of 0.02 was performed, using lithotripsy method as the dependent variable, and age, sex, stone size, and bile duct diameter as independent variables, resulting in well-balanced mechanical and laser lithotripsy groups. Kaplan-Meier survival analysis was used to assess recurrence-free survival, with comparisons performed using the log-rank test. Results:Before PSM, there were significant differences in age, sex, stone length, and bile duct diameter between the groups (all P<0.05). After PSM, 40 patients were included in the mechanical lithotripsy group, 34 in the laser group, and 35 in the combined group, with no significant differences in baseline or preoperative clinical characteristics (all P>0.05). The combined group had a significantly longer operative time compared to the mechanical group [71.0 (66.0, 92.0) min vs. 50.5 (40.4, 56.5) min, Z=-5.02, P<0.001] and the laser group [71.0 (66.0, 92.0) min vs. 53.0 (26.5, 73.5) min, Z=-2.61, P=0.001]. The laser group also had a longer operative time than the mechanical group [53.0 (26.5, 73.5) min vs. 50.5 (40.4, 56.5) min, Z=-2.27, P=0.023]. Hospitalization costs were significantly higher in the combined group compared to the mechanical group [43 000(33 000, 50 000) yuan vs. 30 000(26 000, 37 000) yuan; Z=-3.43, P<0.001]. The single-session stone clearance rates were 80.0% (32/40) for the mechanical group, 85.3% (29/34) for the laser group, and 62.9% (22/35) for the combined group. Postoperative complication rates were 20.0% (8/40), 11.7% (4/34), and 11.4% (4/35), respectively, with no statistically significant differences among the three groups (all P>0.05). There were also no significant differences in cumulative recurrence-free survival among the groups ( χ2=0.06, P=0.970). Conclusions:For endoscopic management of difficult CBD stones, combined lithotripsy is associated with longer operative time and higher hospitalization costs compared to mechanical and laser lithotripsy alone. Laser lithotripsy also requires more operative time than mechanical lithotripsy. However, the three lithotripsy strategies show no significant differences in postoperative complications or cumulative recurrence-free survival.