Journal of Shanghai Jiao Tong University (Medical Science)

Dynamic changes and prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients

YAN Zhi, WU Xingyue, YAO Weiqin, YAN Lingzhi, JIN Song, SHANG Jingjing, SHI Xiaolan, WU Depei, FU Chengcheng

2025, 45 (7): 807-814.
doi: 10.3969/j.issn.1674-8115.2025.07.001

Abstract ( 259 )

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Objective ·To detect immunoglobulin (Ig) expression levels in newly diagnosed multiple myeloma (MM) patients before and after induction therapy, and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy, infection occurrence, and prognosis. Methods ·Clinical data from 142 MM patients treated at the Department of Hematology, The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed. Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone (VRD) regimen were assessed. Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal. Patients were stratified by immunoparesis severity (mild, moderate, severe, extremely severe). ANOVA, rank-sum tests, and χ² tests were used to analyze correlations with baseline characteristics. The relationship between the improvement in immunoparesis and the induction efficacy, infection occurrence, and prognosis was analyzed based on the dynamic changes in immunoparesis. Results ·Normal Igs were severely reduced in newly diagnosed MM patients. Immunoparesis was present in 128 patients (90.1%), with severe or extremely severe immunoparesis accounting for 76.1%. Patients with extensive immunoparesis (all uninvolved Ig levels below the lower normal limit) were more likely to have severe immunoparesis (P<0.05). There were no statistically significant differences in age,gender, presence of severe renal insufficiency, and high-risk cytogenetics among MM patients with different degrees of immunoparesis (P>0.05), but there were statistically significant differences in MM staging (P=0.008) and typing (P=0.010). Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System (R-ISS) and were of the IgG type. At diagnosis, the levels of the involved Ig or light chain were negatively correlated with normal Ig levels (P<0.05). Improvement in immunoparesis after induction therapy was positively correlated with treatment response (P=0.006). The infection rate was high (26.8%), but no significant correlation was found between immunoparesis and infection occurrence (P>0.05). After induction therapy, patients showing improvement in immunoparesis had significantly longer progression-free survival (PFS) (median PFS: not reached vs 38 months, P=0.025), but no significant impact on overall survival (OS) was observed (P=0.450). Conclusion ·Immunoparesis is common and severe in newly diagnosed MM patients, with severity correlating with disease stage and subtype. VRD therapy can partially reverse immunoparesis, and improvement is positively associated with treatment response and PFS benefit. Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies. Humoral immune deficiency may serve as a prognostic indicator in MM, but its impact on OS requires further investigation.

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Efficacy analysis in elderly and frail newly diagnosed multiple myeloma patients with dose-reduced lenalidomide/melphalan/prednisone acetate regimens

ZHANG Xingli, TIAN Jie, LUO Jing, LIU Qian, OUYANG Wanyan, QIU Hongchun, WANG Yan, MI Jianqing

2025, 45 (7): 815-822.
doi: 10.3969/j.issn.1674-8115.2025.07.002

Abstract ( 257 )

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Objective ·To investigate the efficacy and safety of a dose-reduced, all-oral lenalidomide/melphalan/prednisone acetate (RMP) regimen in elderly and frail patients with newly diagnosed multiple myeloma (NDMM). Methods ·Elderly and frail NDMM patients who visited the Department of Hematology of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and the Third People's Hospital of Kunshan from April 2018 to March 2024 were retrospectively included. Clinical data and laboratory indicators were collected, and all patients were treated with the RMP regimen. SPSS 27.0 and R software were used for statistical analysis. Independent t-test was applied to normally distributed quantitative data, Mann-Whitney U test to non-normally distributed quantitative data, and χ² test and Fisher's exact probability method to qualitative data. Kaplan-Meier survival curves and Log-rank test were used for survival analysis. Results ·Among the 22 elderly and frail NDMM patients treated with RMP, the median age was 76.3 (68.4, 95.0) years, and the median follow-up time was 25.5 months. The overall response rate (ORR) was 68.2%, and the rate of ≥ very good partial response (VGPR) was 36.4%. The median progression-free survival (PFS) was 20.53 months. The median PFS in the ≤75-year-old group was 25.23 (95%CI 12.95‒37.52) months, while in the >75-year-old group it was 18.23 (95%CI 14.86‒21.61) months. There was no significant difference between the two groups. The median PFS in the ≥ partial response (PR) group was 20.67 (95%CI 13.57‒27.76) months, and in the < PR group it was 8.53 (95%CI 6.48‒10.59) months, with a statistically significant difference (P=0.011). The median number of treatment courses was 11 (2, 24). The incidence of treatment-related hematological adverse events of all grades was 63.6%, and ≥ grade 3 hematological adverse events occurred in 18.2% of patients. The most common treatment-related adverse event (TRAE) in hematology was neutropenia (63.6%), of which ≥ grade 3 neutropenia accounted for 13.6%. Common non-hematological TRAEs included fatigue (22.7%), respiratory tract infections (18.2%), rash (18.2%), gastrointestinal reactions (18.2%), and thrombosis (13.6%). Six patients (27.3%) required dose reduction or treatment suspension due to severe TRAEs. Conclusion ·The dose-reduced, all-oral RMP regimen is safe and effective in treating elderly and frail NDMM patients and is worthy of clinical application.

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Effect of plasma exchange combined with classical chemotherapy on renal function in patients with multiple myeloma

LIN Tong, TAO Yi, JIN Shiwei, SUN Miao, MI Jianqing

2025, 45 (7): 823-828.
doi: 10.3969/j.issn.1674-8115.2025.07.003

Abstract ( 227 )

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Objective ·To investigate the effect of plasma exchange combined with classical chemotherapy on renal function in patients with multiple myeloma (MM). Methods ·A retrospective analysis was conducted on data from patients newly diagnosed with MM in the Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, between October 2021 and September 2023. Sixty-eight MM patients admitted from October 2021 to September 2022 served as the control group, and 41 patients admitted from October 2022 to September 2023 comprised the experimental group. The control group received classical chemotherapy for MM [PAD (bortezomib+adriamycin+dexamethasone) or PCD (bortezomib+cyclophosphamide+dexamethasone)], and the experimental group underwent plasma exchange before classic chemotherapy. The frequency of plasma exchange was determined according to the clearance rate of M-protein in patients, with the criterion being a reduction of more than 40% in plasma M-protein levels after exchange, and the total number of exchanges ranged from 1 to 3 sessions. After 2 chemotherapy courses, the free light chain difference (dFLC), serum creatinine (Scr), and other renal function indexes were compared between the two groups. Results ·Compared with the control group, the experimental group showed no statistically significant difference in dFLC levels. The Scr level decreased [67.00 (54.00, 75.00) μmol/L vs 77.50 (63.00, 94.00) μmol/L, P=0.011], and the estimated glomerular filtration rate (eGFR) increased [97.80 (92.80, 101.30) mL/(min·1.73 m²) vs 85.80 (61.35, 95.35) mL/(min·1.73 m²), P<0.001] after treatment. Before treatment, the numbers of patients with MM-related severe renal injury [eGFR<50 mL/(min·1.73 m²)] were 41 in the control group and 28 in the experimental group. After treatment, 8 patients (19.51%) in the control group achieved complete renal response [eGFR≥60 mL/(min·1.73 m²)], while 12 patients (42.86%) in the experimental group achieved the same, with the difference being statistically significant (P=0.036). After two courses of treatment, the overall response rates (ORR) of the control group and the experimental group were 76.47% and 92.68%, respectively, and the difference in overall therapeutic efficacy was statistically significant (P=0.031). Conclusion ·Plasma exchange combined with classical chemotherapy can significantly reduce the Scr levels and increase eGFR in MM patients within a short period, ameliorating the MM-related renal impairment to some extent and improving clinical treatment outcomes.

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Efficacy of photo-crosslinked gelatin hydrogel scaffolds loaded with tauroursodeoxycholic acid on knee cartilage defect repair in a rabbit model

WEI Xiang, WEI Lingfei, XU Chunfeng, GAO Yujie, NIE Ping, YU Dedong

2025, 45 (7): 829-837.
doi: 10.3969/j.issn.1674-8115.2025.07.004

Abstract ( 191 )

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Objective ·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated (GelMA) hydrogel scaffolds loaded with tauroursodeoxycholic acid (TUDCA) on cartilage defects in rabbit knee joints. Methods ·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method. The physicochemical properties of GelMA hydrogel scaffolds were characterized, and the cumulative release rate of TUDCA was determined. A rabbit knee cartilage defect model was established, and 18 rabbits were randomly assigned into three groups, with six rabbits in each group: the control group (no treatment was applied to the cartilage defect), the GelMA group (the cartilage defect was filled with GelMA hydrogel scaffold), and the GelMA+TUDCA group (the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA). At 12 weeks postoperatively, the concentrations of two inflammatory factors in synovial fluid, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were detected by enzyme-linked immunosorbent assay (ELISA). After euthanasia, knee cartilage samples were harvested for gross observation, safranin O-fast green staining, and toluidine blue staining. The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society (ICRS) and Modified O′Driscoll Score (MODS) systems. Immunohistochemical staining was performed to detect type Ⅱ collagen (COL-Ⅱ) protein in the cartilage tissue, and Western blotting was used to assess the protein levels of aggrecan (ACAN) and COL-Ⅱ. Results ·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation, along with an suitable mass swelling ratio and compressive modulus. The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release, achieving a cumulative release rate of 90.2%±2.5% within 28 d. ELISA results showed that compared to the control and GelMA groups, the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced (P<0.001). In the GelMA+TUDCA group, the cartilage defects were nearly fully repaired, with a smooth surface and good integration with the surrounding tissue. The number of newly formed chondrocytes increased, displaying orderly alignment, and the neocartilage exhibited excellent formation. Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups (P<0.001). Additionally, the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups (P<0.001). Conclusion ·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

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Effect of Th17-specific Stat3 knockout on anxiety- and depressive-like behaviors in periodontitis mice

ZHOU Yining, YE Zhiyun, CHEN Huiwen, XIE Xinyi, ZHOU Wei, SONG Zhongchen

2025, 45 (7): 838-845.
doi: 10.3969/j.issn.1674-8115.2025.07.005

Abstract ( 302 )

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Objective ·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety- and depressive-like behaviors. Methods ·Mice with specific Stat3 knockout in Th17 cells (Stat3^fl/fl; Il17a-CreERT2), named Stat3^△^Il17a, and wild-type mice (Stat3^fl/fl, WT) were generated through the Cre/LoxP system, and Stat3 knockout was induced by intraperitoneal injection of tamoxifen. CD4⁺T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells. Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency. Mice were assigned into 4 groups: WT-C group, Stat3^△^Il17a -C group, WT-P group, and Stat3^△^Il17a -P group. The periodontitis model was established in the WT-P group and the Stat3^△^Il17a -P group by injection of Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) into the gingival sulcus. Behavioral tests, including the open field test, elevated zero maze, and forced swimming test, were conducted to evaluate changes in anxiety- and depressive-like behaviors. Micro-computed tomography was used to observe destruction of alveolar bone. Neuronal injury was observed by H-E staining, and the level of brain-derived neurotrophic factor (BDNF) was detected by enzyme-linked immunosorbent assay. Results ·mRNA expression and protein levels of Stat3 in Stat3^△^Il17a mice were inhibited compared to WT mice (P<0.05). Experimental periodontitis model was successfully established in the WT-P group and the Stat3^△^Il17a -P group. The degree of alveolar bone destruction was reduced in the Stat3^△^Il17a -P group compared to the WT-P group. In the WT-P group, decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively, and increased immortal time was recorded in the forced swimming test (P<0.05). Moreover, neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group (P<0.05). The degree of abnormal behaviors and neuronal injury was reduced in the Stat3^△^Il17a -P group compared to the WT-P group (P<0.05). Moreover, the level of BDNF in the Stat3^△^Il17a -P was higher than that in the WT-P group (P<0.05). Conclusion ·Periodontitis may contribute to anxiety- and depressive-like behaviors and neuronal damage in mice, while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage. Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

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Expression of PTPRN in lung adenocarcinoma and its mechanism of promoting tumor metastasis

WU Lei, DU Fenglin, ZHAO Mingna, REN Yizhe, ZHANG Xianzhou, LOU Jiatao

2025, 45 (7): 846-857.
doi: 10.3969/j.issn.1674-8115.2025.07.006

Abstract ( 225 )

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Objective ·To investigate the expression of protein tyrosine phosphatase receptor type N (PTPRN) in lung adenocarcinoma and its potential molecular mechanisms in promoting lung adenocarcinoma metastasis. Methods ·A highly bone-metastatic A549-BM cell line was established through multiple rounds of intracardiac injection. RNA sequencing (RNA-seq), combined with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, was performed to identify PTPRN as a key metastasis-related gene. Subsequently, The Cancer Genome Atlas (TCGA) database was utilized to evaluate PTPRN expression in patients with lung adenocarcinoma and its correlation with clinical prognosis. Co-expression analysis based on TCGA data was conducted to identify and analyze key genes co-expressed with PTPRN. Small interfering RNA (siRNA) targeting PTPRN (siPTPRN) was transfected into A549-BM cells, and Transwell assays were performed to assess its effects on cell migration and invasion. Western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and the activation of the PI3K-AKT signaling pathway. siPTPRN-transfected A549-BM cells were injected into a mouse model via intracardiac injection, and in vivo metastasis was assessed. Additionally, multiple database analyses were integrated to predict BCL6 as an upstream transcription factor of PTPRN, and siBCL6 transfection experiments were performed to validate the regulatory effect of BCL6 on PTPRN expression. Results ·RNA-seq and GO/KEGG enrichment analyses demonstrated that PTPRN was significantly upregulated in highly metastatic A549-BM cells and enriched in metastasis-associated pathways, including the PI3K-AKT signaling pathway and extracellular matrix (ECM)-receptor interactions. Analysis of the TCGA database further confirmed that PTPRN was highly expressed in lung adenocarcinoma patients and significantly associated with poor prognosis. Co-expression analysis based on TCGA data, combined with GO/KEGG enrichment analyses, revealed that PTPRN-associated genes were mainly enriched in biological processes such as neural signaling, endocrine regulation, cell communication, and ECM-receptor interactions. In vitro experiments demonstrated that siPTPRN transfection significantly inhibited the migration and invasion of A549-BM cells, accompanied by downregulation of EMT-related proteins and reduced activation of the PI3K-AKT signaling pathway. In vivo experiments further showed that PTPRN knockdown markedly suppressed the metastatic potential of A549-BM cells, confirming its pro-metastatic role. Additionally, siBCL6 transfection experiments demonstrated that BCL6 knockdown upregulated PTPRN expression. Conclusion ·PTPRN is highly expressed in lung adenocarcinoma tissues and promotes tumor cell migration and metastasis by enhancing EMT and activating the PI3K-AKT signaling pathway. High PTPRN expression is significantly correlated with poor prognosis in lung adenocarcinoma patients, while PTPRN enhances lung adenocarcinoma cell invasiveness and metastatic potential. BCL6 may act as an upstream transcriptional regulator of PTPRN, influencing its expression levels.

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Optimization of optimal printing parameters and composition ratio of dental crown and bridge resin based on digital light processing technology

LIU Junlong, MA Jiayin, ZHAO Zhe, XIONG Yaoyang, ZHENG Yuanli

2025, 45 (7): 858-865.
doi: 10.3969/j.issn.1674-8115.2025.07.007

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Objective ·To fabricate a 3D-printed dental crown and bridge resin slurry using digital light processing (DLP) technology, investigate the influence of different printing parameters on its mechanical properties, determine the optimal printing parameters, and optimize the composition ratio of DLP-printed crown and bridge resin. Methods ·Based on the viscosity characteristics of the mixture, the optimal ratio of urethane dimethacrylate (UDMA) to poly (propylene glycol) dimethacrylate (PPGDMA) was explored. After silanizing silicon dioxide (SiO₂), it was mixed with UDMA, PPGDMA, and 2,4,6-trimethylbenzoyl bis (p-tolyl) phosphine oxide (TMO) to prepare DLP-printed dental crown and bridge resin slurries with different solid contents, and their rheological properties were tested. The Beer-Lambert equation was used to calculate the light penetration depth and critical exposure energy of the printing slurry. Based on these values, different exposure intensities, exposure times, post-curing times, and layer thicknesses were set respectively to carry out a series of printing experiments. By comparing and analyzing the flexural strength of the products under different printing parameters, the optimal printing parameter combination was screened out. Results ·Viscosity tests showed that the optimal UDMA-to-PPGDMA ratio was 6∶4. The rheological behavior of printing slurries with different solid contents was tested, and the results showed that the DLP-printed dental crown and bridge resin with a solid content of 22% exhibited the best printing performance. According to the Beer-Lambert analysis, the light penetration depth D_p of the printing slurry was 119.79 μm, and the critical exposure energy E_cwas 25.54 mJ/cm². When the exposure intensity was 20 mW/cm², the flexural strength reached a maximum of (132.39±8.92) MPa, and the difference was statistically significant (P<0.05). The flexural results of different exposure times showed that the flexural strength could reach (131.73±9.43) MPa when the single-layer exposure time was 3.0 s, and there was no significant difference when the exposure time was further increased. The flexural results of different post-curing times showed that when the post-curing time reached 30 min, there was no significant relationship between the flexural strength value and the increase in post-curing time. Regarding the influence of different layer thicknesses on the flexural performance, the test results showed that when the layer thickness was 50 μm, the result was the best, and the difference was statistically significant (P<0.001). Conclusion ·Based on viscosity and rheological tests, a DLP-printable crown and bridge resin slurry was successfully developed. The optimal printing parameters were determined through statistical analysis of flexural strength: exposure intensity of 20 mW/cm², exposure time of 3.0 s, post-curing time of 30 min, and a layer thickness of 50 μm.

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Nanoengineered T cell system for the in vitro treatment of oral squamous cell carcinoma

MENG Jing, XIE Yuting, ZUO Jiaxin, XIONG Ping

2025, 45 (7): 866-873.
doi: 10.3969/j.issn.1674-8115.2025.07.008

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Objective ·To construct a nanoengineered T cell system and explore its synergistic efficacy in the in vitro treatment of oral squamous cell carcinoma, and provide a new strategy for this disease. Methods ·Zr-MOF nanoparticles with a highly hydrophilic hyaluronic acid (HA) coating (PCN224-HA NPs) were prepared, and their carboxyl groups were activated to enable coupling with anti-CD45 antibodies through an amide reaction. High-purity CD8⁺ T cells were then extracted from the spleens of mice, and the PCN224-HA NPs were loaded onto the T cells via the CD45 antigens on their surface. The coupling was observed using bioelectron microscopy and confocal microscopy, and free radical generation was detected under ultrasound irradiation. The viability of Cal27 cells was recorded by a microplate reader to explore therapeutic effects in vitro. Results ·PCN224-HA NPs were successfully synthesized and confirmed to be coupled onto the surface of CD8⁺ T cells, constructing a nanoengineered T cell system (T cells@PCN224-HA NPs). Free radical production was monitored after ultrasound irradiation and the viability of Cal27 cells decreased to 31.70% after in vitro treatment. Conclusions ·Preliminary experiments demonstrated that the nanoparticles can be successfully loaded onto the surface of T cells, providing combined sonodynamic therapeutic effects from the nanoparticles and immunocidal effects from the T cells. This offers a novel strategy for the treatment of oral squamous cell carcinoma, with potential for further in vivo anti-tumor experiments and therapeutic applications.

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A comparative analysis of the short-term efficacy of robotic and laparoscopic proximal gastrectomy combined with double-flap anastomosis in the treatment of early upper gastric cancer

AIMAITI Muerzhate, ZHANG Yeqian, LIU Tao, BAI Long, ZHANG Haoyu, NI Bo, GUAN Yujing, WANG Shuchang, GU Jiayi, ZHU Chunchao, XIA Xiang, ZHANG Zizhen

2025, 45 (7): 874-882.
doi: 10.3969/j.issn.1674-8115.2025.07.009

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Objective ·To compare the safety and short-term outcomes of robot-assisted versus laparoscopic-assisted proximal gastrectomy combined with double-flap esophagogastrostomy in the treatment of early upper gastric cancer. Methods ·A retrospective cohort study was conducted to analyze the clinical and pathological data of 31 early gastric cancer patients who underwent proximal gastrectomy combined with double-flap esophagogastrostomy for gastrointestinal reconstruction at the Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from September 2023 to March 2024. Based on the surgical approach, patients were divided into the robot-assisted surgery group (robotic group, 20 cases) and the laparoscope-assisted surgery group (laparoscopic group, 11 cases). General clinical data, intraoperative conditions, and postoperative recovery between the two groups were compared. At the 6-month postoperative follow-up, upper gastrointestinal radiography and esophagogastroscopy were performed to assess anastomotic stricture and gastroesophageal reflux disease. Additionally, the gastric cancer-specific module of the European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Stomach 22 (QLQ-STO22), was used to evaluate the patients′ quality of life. Results ·The general data of the two groups, including gender, age, preoperative comorbidities, American Society of Anesthesiologists (ASA) classification, Siewert classification, and pathological staging of tumors, showed no statistically significant differences (all P>0.05). All patients successfully underwent the procedure without conversion to open surgery. The time for gastroesophageal anastomosis was significantly shorter in the robotic group compared to the laparoscopic group [(31.09±8.23) min vs (43.73±8.83) min, P<0.001], while there were no statistically significant differences in other intraoperative and postoperative parameters, including operative time, intraoperative blood loss, number of lymph nodes removed, duration of gastric tube placement, time to start a liquid diet, length of postoperative hospital stay, and incidence of postoperative complications (all P>0.05). At the 6-month postoperative follow-up, 30 patients completed the follow-up, with one patient lost to follow-up in the robotic group. Upper gastrointestinal radiography and esophagogastroscopy results showed that only one patient in the laparoscopic group developed an anastomotic stricture, while one patient in the robotic group developed grade A and one developed grade B gastroesophageal reflux disease (GERD). In addition, one patient in the laparoscopic group also developed grade B GERD. The incidences of GERD and anastomotic stricture showed no statistically significant differences between the two groups (both P>0.05). EORTC QLQ-STO22 results indicated that the robotic group had significantly lower scores in the dimensions of dysphagia, gastroesophageal reflux, and dietary restrictions, as well as in the total score, compared to the laparoscopic group (all P<0.05). Conclusion ·Robot-assisted proximal gastrectomy combined with double-flap esophagogastrostomy is safe and feasible. It shortens anastomosis time and offers potential advantages in postoperative functional recovery and quality of life improvement.

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Effects of emotion regulation ability on inhibitory control in patients with alcohol use disorder

CHENG Fei, CHEN Tianzhen, YOU Xu, XUE Baoshuang, YANG Yunbin, DU Jiang

2025, 45 (7): 883-891.
doi: 10.3969/j.issn.1674-8115.2025.07.010

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Objective ·To investigate the performance and psychological mechanisms of inhibitory control in patients with alcohol use disorder (AUD) under different emotional contexts, and to examine the influence of emotion regulation difficulties on inhibitory control. Methods ·A total of 28 male AUD inpatients (AUD group) and 28 age- and education-matched healthy controls (HC group) were recruited. The emotional Go/Nogo task (angry/neutral facial expressions) was used to evaluate the subjects' behavioral inhibition, and the hierarchical drift-diffusion model (HDDM) was used to quantify the cognitive parameters (drift rate, decision threshold, and non-decision time). The Difficulties in Emotion Regulation Scale (DERS) and Alcohol Use Disorder Identification Test (AUDIT) were used for clinical evaluation. The moderated mediation effects were tested by bootstrap method. Results ·The AUD group scored higher than the HC group on the DERS total score and all sub-dimensions (goal-directed behavior, impulse control, strategy access, and emotional clarity), and the difference was statistically significant (all P<0.05). At the behavioral level, compared with the HC group, the AUD group had elevated commission error rates [F_(1,54)=8.62, P=0.005] and omission error rates [F_(1,54)=4.28, P=0.043], and the reaction time of angry face stimuli was generally prolonged [F_(1,54)=12.26, P=0.001]. Cognitive modeling showed that the drift rate of the AUD group was significantly lower than that of the HC group [F_(1,54)=15.56, P<0.001], indicating impaired information processing efficiency. The moderated mediation model showed that, under the condition of angry face stimuli, the drift rate partially mediated the relationship between group and commission error rate, and the total indirect effect value was 9.564 (95%CI 3.874‒16.387). Further analysis showed that the conditional indirect effect increased to 10.133 (95%CI 3.963‒17.927) at high levels of emotion regulation difficulty (one standard deviation above the mean), and to 9.011 (95%CI 3.778‒14.921) at low levels (one standard deviation below the mean). Conclusion ·The deficits in information processing efficiency of AUD patients partly explains the impairment of inhibitory control, and this effect is associated with individual emotion regulation capacity. It is suggested that abnormal processing of social threat information may be an important factor affecting the impairment of inhibitory control in AUD patients, especially in individuals with weak emotion regulation ability.

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Clinicopathological features of 12 cases of epithelioid hemangioendothelioma

SUI Chengliang, SHEN Yanying, LIU Zebing

2025, 45 (7): 892-899.
doi: 10.3969/j.issn.1674-8115.2025.07.011

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Objective ·To investigate the clinical, pathological, and molecular genetic features and prognosis of epithelioid hemangioendothelioma (EHE) patients. Methods ·Clinical and follow-up data of 12 EHE patients diagnosed at Renji Hospital, Shanghai Jiao Tong University School of Medicine from September 2016 to December 2023 were collected. Tissue samples were analyzed using hematoxylin-eosin (H-E) staining, immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH). Results ·Among the 12 patients, there were 3 males and 9 females, with a mean age of (47.17±11.15) years. Tumors were located in the liver (6 cases), lung (4 cases), mediastinum (1 case), and supraclavicular region (1 case). Nine patients were asymptomatic, while 3 presented with mild symptoms such as chest tightness and fatigue. CT imaging revealed that EHE patients with involvement of livers and lungs exhibited multiple nodules, and 2 cases had tumors in both organs. Patients with tumors in the supraclavicular region and mediastinum presented with solitary nodules. H-E staining demonstrated that tumor tissues were composed of epithelioid, dendritic, and intermediate cells, arranged in acinar, cord-like, or clustered patterns. Epithelioid cells had round vesicular nuclei and eosinophilic cytoplasm, with some showing a signet-ring appearance and cytoplasmic vacuoles. The stroma contained a mucoid matrix. IHC staining revealed that mesenchymal endothelial markers, including vimentin, CD31, ETS transcription factor ERG, and factor Ⅷ-related antigen, were positive in the tumor tissues, while epithelial markers showed low positivity with weak staining. The Ki-67 indexes were also low. FISH analysis showed that 10 patients had a calmodulin-binding transcription activator 1 (CAMTA1) gene break, while 2 patients had a transcription factor E3 (TFE3) gene break. Of the 12 patients, 11 were followed up for 2 to 38 months, with a mean follow-up time of 21.7 months. Three patients achieved tumor-free survival, 6 were alive with tumors, 1 died 4 months after surgery, and 1 died of heart disease 24 months after surgery. Conclusion ·EHE has atypical clinical features, a tendency to recur, a and variable prognosis. Accurate diagnosis requires a combination of histopathology, IHC, and a molecular testing.

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Application value of synthetic magnetic resonance imaging in predicting cervical lymph node metastasis of oral cancer

WANG Rui, YUAN Ying, TAO Xiaofeng

2025, 45 (7): 900-909.
doi: 10.3969/j.issn.1674-8115.2025.07.012

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Objective ·To explore the value of synthetic magnetic resonance imaging (SyMRI) technology in the diagnosis of cervical lymph node metastasis in patients with oral cancer. Methods ·A retrospective analysis was conducted on patients admitted to Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, from November 2023 to April 2024, who were pathologically diagnosed with oral cancer and had a clear lymph node metastasis status. Pre-operative maxillofacial magnetic resonance images of these patients were collected. Histogram features were extracted and screened from the quantitative maps generated by SyMRI, including synthetic T1, T2, and proton density (PD) maps, apparent diffusion coefficient (ADC) maps, and volumes of interest (VOIs) from contrast-enhanced images. The optimal range was determined by comparing the histogram parameters of different peritumoral regions. On this basis, habitat analysis was further carried out by combining the quantitative maps and ADC maps, and the habitat features of the tumor invasive sub-regions were extracted to construct a prediction model. The performance of the model was comprehensively evaluated using receiver operator characteristic curves (ROC curves), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Results ·A total of 61 patients with oral cancer were included in the study. The area under the curve (AUC) value for predicting cervical lymph node metastasis based on the intratumoral histogram features extracted from SyMRI was 0.798 (95%CI 0.673‒0.924). Adding the ADC map could increase the AUC value to 0.818 (95%CI 0.635‒0.861). By combining the histogram features from the 12-mm peritumoral region with habitat features, the AUC value for predicting lymph node metastasis could be further increased to 0.907 (95%CI 0.812‒0.993). The analysis results of NRI, IDI, and DCA all showed that the predictive performance of the model was better than that of clinical diagnosis. Conclusion ·Based on SyMRI, combining the histogram features from the intratumoral and peritumoral regions with habitat features shows high performance in the prediction of lymph node metastasis in oral cancer, providing a feasible, contrast agent-free approach for rapid imaging and prediction of metastatic lymph nodes.

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Research progress of arginine metabolism in the regulation of mesenchymal stem cell function

KERANMU Saitierguli, QIAN Lei, DING Siyi, MAHELIMUHAN Hanati, YANG Xueer, JIA Hao

2025, 45 (7): 910-915.
doi: 10.3969/j.issn.1674-8115.2025.07.013

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Mesenchymal stem cells (MSCs) are adult stem cells that exist in bone marrow, fat, cord blood, bone, muscle and other tissues. MSCs not only have the unique self-renewal ability and multidirectional differentiation potential of stem cells, but also have the function of immune regulation. Arginine is a conditionally essential amino acid, and its metabolic regulation is essential for maintaining cell function and overall health. In MSCs, arginine metabolism may have a certain effect on cell proliferation, differentiation, inflammatory response, and tumor development. This article summarizes the effects of arginine metabolism on the differentiation, inflammation, immunity, and tumor development in different types of MSCs, discusses new strategies for the treatment of metabolic syndrome, and provides new ideas for the treatment of inflammatory diseases and tumors by MSCs from the perspective of arginine metabolism.

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Research progress on immune cell therapy in renal cell carcinoma

CHEN Zixuan, LIU Min

2025, 45 (7): 916-925.
doi: 10.3969/j.issn.1674-8115.2025.07.014

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Renal cell carcinoma (RCC) is the most common type of malignant kidney tumor in adults, accounting for more than 90% of all renal malignancies. In its early stages, RCC is often asymptomatic and is frequently discovered incidentally during physical examinations or diagnostic imaging. While localized RCC can often be effectively treated with surgical resection, the prognosis for advanced or metastatic cases remains poor, as conventional therapies such as chemotherapy, radiotherapy, and targeted therapy often show suboptimal responses. As a highly immunogenic tumor, RCC is capable of evading immune surveillance through various mechanisms. Therefore, immune therapies, especially cell-based therapies at the forefront, have gained significant attention in recent years as emerging treatment modalities, showing great potential. Immune cell therapy enhances anti-tumor immune responses by utilizing the patient's immune system or exogenous immune cells to restore immune function, thereby effectively eliminating tumor cells. It has become an important research direction for RCC treatment. However, despite its promising clinical prospects, immune cell therapy still faces numerous challenges. Issues such as individual heterogeneity, immune-related adverse events, immune suppression in the tumor microenvironment, and post-treatment drug resistance continue to affect its clinical efficacy. This review summarizes the immune escape mechanisms in RCC, outlines the progress of RCC immune cell therapy, and analyzes its future prospects, aiming to provide insights and direction for better addressing the clinical challenges of refractory RCC.

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Research progress in effects and mechanisms of dietary pattern interventions in metabolic associated fatty liver disease

SONG Jing, JIANG Shuo, WAN Fangyu, LI Juan, MUHETA Adina, MIN Xinying, ZHOU Jingqi

2025, 45 (7): 926-933.
doi: 10.3969/j.issn.1674-8115.2025.07.015

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Metabolic associated fatty liver disease (MAFLD) is a type of fatty liver disease associated with systemic metabolic disorders, and its prevalence has been increasing year by year, becoming a major challenge to global public health. The development of MAFLD is associated with various factors, including obesity, dyslipidemia, diabetes and other factors. Excessive body fat, particularly increased visceral adiposity, contributes to hepatic fat accumulation. Abnormal blood lipid levels can also disrupt liver fat metabolism. The risk of MAFLD in patients with diabetes is greatly increased due to insulin resistance and other problems. Dietary interventions are considered an effective strategy for the prevention and treatment of MAFLD. In recent years, several dietary patterns, such as low-carbohydrate diets, intermittent fasting, and the Mediterranean diet, have been applied in clinical practice. Their primary mechanisms include reducing oxidative stress, regulating gut microbiota, and inducing fat autophagy. However, the responses to different dietary patterns vary among individuals due to differences in genes, lifestyle, and disease severity. Therefore, systematically evaluating the effects and mechanisms of these dietary patterns in the prevention and treatment of MAFLD has significant clinical importance. This review compares the effects of different dietary patterns on improving liver function, hepatic fat content, blood glucose, and lipid levels, and analyzes their underlying mechanisms of intervention, to explore how to select personalized dietary strategies based on individual differences. It is intended to provide new insights for the precise prevention and treatment of MAFLD, thereby improving patients′ outcomes and alleviating the burden on public health.

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A case report of neonatal pseudoaldosteronism caused by NR3C2 gene mutation

LI Junhe, ZHANG Rui, LIU Qingxu, SUI Sumin

2025, 45 (7): 934-938.
doi: 10.3969/j.issn.1674-8115.2025.07.016

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Pseudohypoaldosteronism type Ⅰ (PHA Ⅰ) is a rare inherited disease, mainly caused by the deficiency of the aldosterone receptor or by reduced or absent binding between aldosterone and its receptor. It typically manifests as neonatal hyponatremia, hyperkalaemia, metabolic acidosis, accompanied by dehydration, vomiting, weight loss, and even shock. PHA Ⅰ is classified into renal-type with mutations in the salt corticosteroid receptor and multi-organ with mutations in any of the three subunits of the epithelial sodium channel (α, β or γ). The renal-type, which is inherited in an autosomal dominant manner, is caused by mutations in the aldosterone receptor with an isolated nephrogenic salt-loss syndrome, and the clinical symptoms are milder compared with those of the multi-organ type, which may improve with age. However, severity varies among individuals depending on the degree of salt loss, and if not treated in time, it may lead to shock due to repeated dehydration or even cardiac arrest due to high potassium. Currently, domestic studies have found that the human salt corticosteroid receptor is encoded by the NR3C2 gene, which is located between the regions of 4q31.1 and 4q31.2. This case reports a child with nephrogenic PHA Ⅰ due to a new-onset variant of the NR3C2 (4q31.22) gene, who had chromosomal anomalies in the fetus and demonstrated high blood pressure, high blood potassium and low sodium after birth. The diagnosis of renal neonatal PHA Ⅰ was confirmed by the presence of a microdeletion of NR3C2 gene (4q31.22 region) in the child, which was demonstrated by a genome-wide chromosomal assay and accompanied by a significant elevation of the plasma aldosterone level (>2 000 pg/mL), and by the presence of a microdeletion of NR3C2 gene (4q31.22 region) in the child. Electrolyte disorders were corrected after oral administration of concentrated sodium chloride, and the condition remained stable at the 1-month follow-up.

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