To investigate changes in the depressive disorder burden in China, global, and across socio-demographic index (SDI) regions during the COVID-19(from 2019 to 2021) compared with 1990 to 2019, and to analyze sex-regional disparities.

Using depressive disorder data from the Global Burden of Disease (GBD) database (from 1990 to 2021) for China, global populations, and 5 SDI regions, we characterized depressive disorder burden distribution during the pandemic via metrics including age-standardized prevalence rate (ASPR), age-standardized disability-adjusted life years (ASR-DALYs), and estimated annual percentage change (EAPC). Joinpoint regression modeled temporal trends, and the Bayesian age-period-cohort (BAPC) model estimated the excess depressive disorder burden attributable to COVID-19 in 2020—2021.

China’s depressive disorder ASPR increased to 2 875.68/100 000 person-years (95%CI: 2 589.96 to 3 203.43) in 2021 from 2 825.00/100 000 (95%CI: 2 550.42 to 3 136.08) in 2019; ASR-DALYs rose to 430.61/100 000 (95%CI: 305.24 to 586.21) from 430.14/100 000 person-years (95%CI: 303.92 to 580.82). Joinpoint analysis identified an inflection point for China’s ASPR in 2019, with a significant upward annual percentage change (APC=0.95, P<0.05) from 2019 to 2021—a smaller increase than global and other SDI regions. No significant inflection was observed for China’s ASR-DALYs, whereas other regions showed clear upward inflection points near 2019 (P<0.05). China exhibited the lowest excess depressive disorder burden due to COVID-19: excess ASPR was 121.67/100 000 and excess ASR-DALYs was 12.25/100 000 person-years in 2021, only 28% and 14% of global levels, respectively. Females had higher ASPR/ASR-DALYs and excess burden than males, with females in high-SDI regions bearing the heaviest burden.

COVID-19 imposed severe excess depressive disorder burdens worldwide. China’s effective pandemic response policies and psychological assistance measures mitigated this burden. Countermeasures　Governments should increase investment in mental healthcare resources, enhance public mental health literacy, and ensure rapid implementation of containment measures during public health emergencies—including regular information updates to stabilize public sentiment—alongside community-based psychological support.

To analyze the status and trends of the burden of adverse effects of medical treatment (AEMT) in China from 1990 to 2023 using open data from the Global Burden of Disease (GBD) 2023.

Based on the GBD 2023 data, we extracted the number of incident cases, prevalent cases, disability-adjusted life years (DALYs), and deaths due to AEMT in China from 1990 to 2023. We also extracted age-standardized rates, including the age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized DALYs rate (ASDR), and age-standardized mortality rate (ASMR). The annual percent change (APC), average annual percent change (AAPC), and their 95% confidence intervals (95% CI) for ASIR, ASPR, ASDR, and ASMR were calculated to analyze trends in the burden of AEMT in China. Epidemiological characteristics and differences in the AEMT burden among different age and sex groups in China were compared for the years 1990, 2020, and 2023.

From 1990 to 2023, the number of incident cases, prevalent cases, DALYs, and deaths due to AEMT in China changed from 432 784 (95%UI:347 489 to 526 244), 33 087 (95%UI: 24 103 to 42 381), 686 404(95%UI:398 451 to 1 086 894), and 11 426(95%UI:7 233 to 17 456) to 342 349(95%UI: 279 429 to 423 443), 26 165(95%UI: 19 529 to 33 662), 121 245(95%UI: 90 707 to 155 623), and 3 337(95%UI: 2 494 to 4 212) in 2020, and further to 372 069 (95%UI: 303 152 to 464 618), 28 436 (95%UI: 21 029 to 36 643), 107 384(95%UI, 79 527 to 137 417), and 3 128 (95%UI: 2 305 to 3 985) in 2023. From 1990 to 2023, the AAPC values for ASIR, ASPR, ASDR, and ASMR were -0.994 8%(95%CI: -1.199 7% to -0.789 5%), -0.993 3%(95%CI: -1.202 2% to -0.783 9%), -5.968 4%(95%CI: -6.195 9% to -5.740 3%), and -5.432 2% (95%CI: -5.658 8% to -5.205 1%), respectively (P<0.05). In 1990, incidence and mortality rates were higher in younger age groups and among females compared to males, while rates were higher among older males compared to older females. In 2020 and 2023, incidence was higher among females than males in younger age groups and higher among older males than older females; the differences in incidence rates between males and females within the same age group and year narrowed compared to 1990, while mortality among older males remained higher than among females in the same periods.

From 1990 to 2023, key indicators of the AEMT burden in China-incidence, prevalence, DALYs, and mortality-showed an overall declining trend. Among the elderly population, AEMT incidence and mortality increased with age, and elderly males were more likely to die from AEMT than elderly women. Countermeasures　Enhancing investment in medical training and resources to improve the capability for diagnosing and treating AEMT, continuously strengthening AEMT prevention and control, and implementing tailored interventions for the elderly, particularly elderly males.

To screen novel molecular glues targeting ovarian tumor domain deubiquitinase with linear linkage specificity (OTULIN) and provide a new therapeutic strategy for gastric cancer.

Gastric cancer cell lines with high OTULIN expression (AGS-NC, SNU601-NC) and OTULIN-knockout cells (AGS-sgOTULIN, SNU601-sgOTULIN) were used. Experimental groups included: control (DMSO), LTL-04-061 concentration gradients (0.1, 0.3, 1.0, 3.0, 5.0, 7.0, 10.0 μmol/L), and proteasome inhibitor intervention (MG-132/MLN4924+5 μmol/L LTL-04-061). OTULIN protein expression was analyzed by Western blotting, while mRNA levels were quantified by qPCR. Protein interactions were validated by co-immunoprecipitation (Co-IP). Molecular docking and 100 ns molecular dynamics (MD) simulations were performed to analyze complex conformations. Anti-proliferative effects were assessed using CCK-8, cell proliferation, and colony formation assays.

LTL-04-061 degraded OTULIN protein in a concentration-dependent manner (0.1 to 10.0 μmol/L), with significant degradation at 5 μmol/L. At this concentration, OTULIN mRNA levels remained unchanged (P>0.05). Degradation was blocked by MG-132/MLN4924, indicating dependence on the CRBN-mediated ubiquitin-proteasome pathway. Co-IP confirmed LTL-04-061-induced OTULIN-CRBN ternary complex formation. Key interactions involved OTULIN HIS339 and CRBN TRP378/HIS380. MD simulations showed stable complex conformation after 50 ns (RMSD fluctuation <0.1 nm), sustained hydrogen bonds (80 to 100 ns), and stable radius of gyration (Rg) and solvent-accessible surface area (SASA), indicating no structural expansion/collapse. LTL-04-061 concentration-dependently suppressed gastric cancer cell proliferation and colony formation. CCK-8 assays revealed IC₅₀ values of 8.95 μmol/L (AGS) and 11.70 μmol/L (SNU601). OTULIN knockout significantly attenuated this inhibition (P<0.01).

OTULIN exerts pro-oncogenic effects in gastric cancer. The molecular glue LTL-04-061 targets OTULIN for CRBN-dependent ubiquitin-proteasomal degradation, thereby suppressing malignant proliferation. This identifies LTL-04-061 as a promising precursor for molecularly targeted gastric cancer therapy.

To investigate the mechanism of bone marrow-derived mesenchymal stem cells (MSCs) in alleviating severe acute pancreatitis (SAP) by inhibiting the pyroptosis pathway in a rat model.

Bone marrow-derived MSCs were isolated from 4-week-old male SPF SD rats [body weight, (100±20) g] using the bone marrow flush technique, followed by culture and characterization. Twenty-four male SPF SD rats [body weight (200±20) g] were randomly assigned to four groups (n=6 per group) using a random number table: a sham-operated group, an SAP model group, an ulinastatin-treated group, and an MSCs-treated group. SAP was induced in the latter three groups via retrograde injection of 5%sodium taurocholate into the biliopancreatic duct. The SAP model group received an injection of 100 μL PBS at 12 h post-modeling. The ulinastatin-treated group received an intraperitoneal injection of ulinastatin solution (5×10⁴ U/kg) immediately after model induction. The MSCs-treated group received an injection of MSC suspension (5×10⁶ cells/kg) at 12 h post-modeling. Sham-operated rats underwent laparotomy with gentle pancreatic manipulation before abdominal closure. Pancreatic histopathology was assessed by HE staining and pathological scoring. Serum amylase and lipase activities were measured using commercial assay kits. Serum levels of IL-10, IL-1β, and TNF-α were determined by ELISA. The ultrastructural changes of pancreatic acinar cells were observed under transmission electron microscopy (TEM). Protein expression of NLRP3, GSDMD, and caspase-1 in pancreatic tissue was evaluated by immunofluorescence. The mRNA levels of NLRP3, GSDMD, and caspase-1 were quantified by qRT-PCR. The relative protein expression levels of NLRP3, GSDMD, GSDMD-N, caspase-1, cleaved caspase-1, and IL-1β were analyzed by Western blotting.

The isolated cells exhibited a typical adherent, spindle-shaped, fibroblast-like morphology. Flow cytometry confirmed they were highly positive for the mesenchymal marker CD29 (99.22%) and nearly negative for the hematopoietic marker CD45 (0.42%). These cells also demonstrated osteogenic and adipogenic differentiation potential and were maintained in good condition. Compared with the sham-operated group, the SAP model group showed significantly increased pancreatic histopathological scores, elevated serum amylase and lipase activities, higher levels of pro-inflammatory cytokines (IL-1β and TNF-α), and a lower level of IL-10 (all P<0.000 1). Both ulinastatin and MSCs treatment significantly attenuated these changes, reducing histopathological scores, serum enzyme activities, IL-1β, and TNF-α (P<0.001), while increasing IL-10 (P<0.05). Importantly, the MSCs-treated group showed significantly greater improvement in all these metrics compared to the ulinastatin-treated group (P<0.05). TEM analysis revealed that MSCs treatment promoted the recovery of mitochondrial cristae structure, improved overall organelle morphology, and reduced endoplasmic reticulum swelling in acinar cells, with these restorative effects being more pronounced than in the ulinastatin group. The immunofluorescence results showed that compared with the SAP model group, the expression levels of NLRP3, GSDMD, and caspase-1 in pancreatic tissue were decreased in both the MSCs-treated group and the ulinastatin-treated group (P<0.000 1). Western blot results indicated that, compared with the SAP model group, the relative protein expression levels of NLRP3, GSDMD, GSDMD-N, caspase-1, cleaved caspase-1, and IL-1β in pancreatic tissue were reduced to varying degrees in both the MSCs-treated group and the ulinastatin-treated group (P<0.000 1). qPR-PCR results demonstrated that, compared with the SAP model group, the mRNA expression levels of NLRP3, GSDMD, and caspase-1 in pancreatic tissue were significantly decreased in both the MSCs-treated group and the ulinastatin-treated group (P<0.01). Moreover, compared with the ulinastatin-treated group, the MSCs-treated group exhibited a more significant decrease in all the aforementioned indicators (P<0.001).

Mesenchymal stem cells alleviate inflammation and tissue damage in severe acute pancreatitis. Their protective mechanism involves inhibiting the NLRP3/GSDMD/IL-1β signaling axis, thereby suppressing acinar cell pyroptosis.

To systematically characterize tumor microenvironmental features and spatial cellular interactomes associated with distinct transcriptional meta-program (MP) in gastric cancer, and explore their clinical implications.

We integrated 2 gastric cancer single-cell RNA sequencing (scRNA-seq) datasets to identify malignant cell-derived transcriptional MP. The prognostic value was validated in 3 independent bulk transcriptomic cohorts: The Cancer Genome Atlas (TCGA), GSE15459, and GSE66229. Using scRNA-seq, we dissected MP-specific shifts in microenvironmental cell composition and inferred dominant ligand-receptor interactions. Spatial transcriptomics confirmed the co-localization of implicated cell subsets and signaling pairs. Survival analyses were used to access the associations between key cellular signatures/interaction signatures and patient outcomes.

Four MP from MP1 to MP4 were identified in malignant cells. High expression of MP2 and MP4 significantly correlated with worse overall survival (P<0.05). In MP2-high tumors, SPP1⁺ macrophages were enriched and predicted to interact with T3 neutrophils via the SPP1-CD44 ligand-receptor pair, with spatial co-localization validated. Both SPP1⁺ macrophage signature (P=0.007) and SPP1-CD44 interaction signature (P=0.008) predicted adverse prognosis. In MP4-high tumors, myofibroblastic cancer-associated fibroblast (myCAF) were expanded and showed interaction with exhausted CD8⁺ T cells through the COL6A family-ITGB1 signaling axis, which was also spatially validated. The myCAF signature (P=0.001) and COL6A family-ITGB1 interaction signature (P<0.001) correlated with poorer survival.

MP2 and MP4 delineate 2 distinct immunosuppressive spatial niches in gastric cancer: SPP1⁺ macrophage-T3 neutrophil and myCAF-exhausted CD8⁺ T cell. These niches likely drive tumor progression via SPP1-CD44 and COL6A family-ITGB1 axes, respectively, providing potential targets for precision immunotherapy.

To investigate whether the MHC-Ⅰ humanized mouse model (AAD mice) combined with the Plasmodium berghei transgenic strain expressing Plasmodium falciparum circumsporozoite protein (PfCSP,Pb-PfCSP) can be used to establish an evaluation model for PfCSP-based vaccines.

AAD mice and C57BL/6J mice (6 to 8 weeks old, body weight 20 to 35 g, 4 mice per group) were challenged with graded doses (200, 500, and 1 000) of Pb-PfCSPsporozoites and wild-type P.berghei (Pb) sporozoites via tail vein injection. The susceptibility of the 2 mouse strains to Pb and Pb-PfCSP infection was compared by monitoring the onset time of erythrocytic-stage parasitemia and the dynamic changes in parasitemia levels. Flow cytometry was performed to analyze the frequency and absolute number of major hepatic immune cell subsets in the 2 mouse strains, so as to preliminarily explore the potential mechanisms underlying the differential susceptibility to malaria parasites. For vaccine efficacy evaluation, 4 AAD mice per group were immunized with either CI-679-attenuated Pb-PfCSP sporozoite vaccine or LNP-encapsulated mRNA vaccine encoding PfCSP (PfCSP@LNP), with unimmunized AAD mice as the control group. After immunization, all mice were challenged with Pb-PfCSP sporozoites, and the protective efficacy was evaluated. The frequency and number of CSP-specific tissue-resident memory T cells (Trm) in the liver were detected by flow cytometry, and CSP-specific antibody titers in serum were measured by enzyme-linked immunosorbent assay (ELISA).

Pb-PfCSP sporozoites at all tested doses successfully infected both AAD and C57BL/6J mice. Compared with C57BL/6J mice, AAD mice exhibited higher susceptibility to both Pb and Pb-PfCSP infection, as evidenced by earlier onset of erythrocytic-stage parasitemia and significantly higher parasitemia levels in the mid-stage of infection (P<0.05). Regardless of infection status, the frequency and absolute number of hepatic natural killer T (NKT) cells in AAD mice were significantly lower than those in C57BL/6J mice (P<0.05), which might be one of the reasons for the increased susceptibility of AAD mice to malaria parasite infection. After challenge with Pb-PfCSP sporozoites, PfCSP@LNP-immunized AAD mice exhibited delayed erythrocytic-stage parasitemia onset compared with the control group, and detectable titers of CSP-specific antibodies were observed in their serum; however, PfCSP-specific Trm cells were not detected in the liver. Similarly, AAD mice immunized with the nitroquine-attenuated Pb-PfCSP sporozoite vaccine only achieved a protective efficacy of 16.6%, and PfCSP-specific Trm cells were not detected either.

The Pb-PfCSP-infected AAD mouse model can be used for evaluating the efficacy of PfCSP-based vaccines in inducing CSP-specific antibody responses. However, this model requires further optimization for assessing PfCSP-specific CD8⁺ T cell response induction.

To investigate the effects of autologous fecal microbiota transplantation (AFMT) on immune regulation and tumor suppression in a murine model of colitis-associated colorectal cancer (CAC) induced by azoxymethane (AOM)/dextran sulfate sodium (DSS), with mechanistic emphasis on NF-κB pathway inhibition and CD8⁺ T cell/regulatory T cell (Treg) balance modulation.

Six-week-old female BALB/c mice [SPF grade, body weight (20±2) g] were randomly divided into 3 groups (n=5 per group): control group (Con), CAC model group (Mod), and AFMT intervention group (AFMT). The CAC model was established by a single intraperitoneal injection of AOM (10 mg/kg) followed by three cycles of DSS treatment (each cycle: 3.5%DSS in drinking water for 7 d plus 14 d of recovery with sterile water). Starting from day 7 post-modeling, the AFMT group received 0.1 mL of autologous fecal microbiota suspension via oral gavage every other day until the end of the experiment; control groups received equal volumes of sterile saline. At endpoint, colorectal tissues, spleen, serum, and fecal samples were collected. Colonic pathological injury and inflammatory cell infiltration were assessed by hematoxylin-eosin (HE) staining. NF-κB p65 and p-NF-κB p65 protein expression in colon tissue was detected by Western blot. Serum TNF-α levels were measured by ELISA. Flow cytometry was used to analyze the proportions of CD8⁺ T cells and regulatory T cells (Treg, defined as CD4⁺CD25⁺Foxp3⁺) in the spleen. Gut microbiota composition and diversity (α- and β-diversity) were analyzed by 16S rRNA sequencing.

Compared with the Con group, the Mod group showed a reduction in goblet cells and significant inflammatory cell infiltration in HE-stained colon sections, an increased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (P<0.05), elevated serum TNF-α levels (P<0.001), a decreased proportion of CD8⁺ T cells in the spleen (P<0.001), an increased proportion of Treg cells (P<0.05), an increased relative abundance of Bacteroidales (P<0.05), and a decreased relative abundance of Lactobacillales (P<0.05). Compared with the Mod group, the AFMT group showed milder structural damage and reduced inflammatory cell infiltration in the colon, a decreased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (P<0.01), reduced serum TNF-α levels (P<0.01), an increased proportion of CD8⁺ T cells in the spleen (P<0.05), a decreased proportion of Treg cells (P<0.05), a decreased relative abundance of Bacteroidales (P<0.05), and an increased relative abundance of Lactobacillales (P<0.05).

AFMT intervention may alleviate disease progression in CAC model mice through multiple mechanisms: restoring the abundance of Lactobacillales, enhancing the intestinal barrier function and promoting short-chain fatty acid production, inhibiting the NF-κB inflammatory pathway, reducing TNF-α levels, and regulating T-cell immune balance.

To investigate CXCL12 therapeutic potential in endometrial repair post intrauterine adhesion (IUA) surgery.

A murine model of IUA was established using mechanical curettage. A total of 48 healthy female C57BL/6 mice (aged 7 to 8 weeks, weighing 18 to 20 g) were randomly allocated to 4 groups (n=12 per group): the sham-operated group (Sham), the model group (Model), the umbilical cord mesenchymal stem cell treatment group (UC-MSCs treatment group), and the CXCL12 treatment group. In the Sham group, only the abdominal wall was incised without intrauterine manipulation. In the Model group, after mechanical curettage, 100 μL of normal saline was infused into the uterine cavity. In the UC-MSCs treatment group, after curettage, 100 μL of UC-MSCs suspension (1×10⁶ cells) was infused into the uterine cavity. In the CXCL12 treatment group, after curettage, 100 μL of CXCL12 solution (containing 200 ng CXCL12) was infused into the uterine cavity. At 7 d post-modeling, histological examination was performed to confirm model establishment, and immunofluorescence staining was used to assess the chemotactic effect of CXCL12 on MSCs. At 21 d post-modeling, hematoxylin and eosin (HE) staining was used to evaluate endometrial thickness and gland number; Masson’s trichrome staining assessed the extent of endometrial fibrosis. Immunohistochemical staining was employed to determine the microvessel density (MVD) and the expression levels of VEGF, Ki-67, and Sirt1. Spearman correlation coefficient was used to assess the correlation between Sirt1 expression levels and endometrial fibrosis.

At 7 d post-modeling, histological examination confirmed the successful establishment of the IUA mouse model. Immunofluorescence staining demonstrated significantly increased MSC homing to the endometrium in both the CXCL12 and UC-MSCs treatment groups versus the Sham and Model groups (P<0.001), with no significant difference between the 2 treatment groups. At 21 d post-modeling, both the CXCL12 and UC-MSCs treatment groups exhibited significantly greater endometrial thickness (P<0.001) and gland number (P<0.05) relative to the Model group. Endometrial fibrosis was significantly reduced in the treatment groups compared with the Model group (P<0.001). Microvessel density (MVD) was significantly higher in the CXCL12 and UC-MSCs groups than in the Model group (P<0.05). Immunohistochemical analysis revealed significantly elevated expression of VEGF (P<0.001), Ki-67 (P<0.001), and Sirt1 (P<0.001) in both treatment groups versus the Model group. After controlling for group allocation, Sirt1 expression showed a significant negative correlation with endometrial fibrosis area (r_s=-0.73, P<0.05, t=-3.86).

Through enhancing MSC homing to the endometrium in IUA mice, CXCL12 exerts therapeutic effects comparable to UC-MSCs therapy, effectively promoting endometrial regeneration and reducing stromal fibrosis, with upregulated Sirt1 expression potentially mediating these effects.

To investigate the mechanism of stigmasterol, an extract from Coicis Semen, in treating rats with a chronic obstructive pulmonary disease (COPD) model.

Forty healthy male SD rats (body weight:120±10 g) were randomly divided into four groups (n=10) using a random number table: blank control (NC) group, model (Mock) group, Stigmasterol group (stigmasterol 20 mg/kg), and stigmasterol+GW9662 group (stigmasterol 20 mg/kg+peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662 1 mg/kg). The COPD rat model was established by smoke exposure combined with intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg). After 14 d of intervention, alveolar macrophages were isolated. M1/M2 polarization was analyzed by flow cytometry; PPARγ expression was detected using qRT-PCR, Western blot, and ELISA; macrophage oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured with a Seahorse XF Analyzer; and lung tissue pathology and macrophage infiltration were observed via HE staining and immunohistochemistry.

Compared with the NC group, the Mock group exhibited a significantly increased M1/M2 ratio (P<0.01), markedly reduced PPARγ expression at both mRNA and protein levels (P<0.001), and decreased mitochondrial basal OCR, maximal OCR, and glycolytic ECAR in alveolar macrophages (P<0.01). Lung tissues showed typical histopathological damage, including alveolar destruction and inflammatory cell infiltration. Stigmasterol intervention reversed these abnormalities by decreasing the M1/M2 ratio (P<0.01), upregulating PPARγ expression (P<0.01), improving mitochondrial respiration and glycolytic capacity (as indicated by OCR and ECAR), and alleviating lung tissue histopathological damage (P<0.05). However, co-administration of the PPARγ antagonist GW9662 significantly attenuated stigmasterol’s beneficial effects on promoting M2 macrophage polarization, upregulating PPARγ expression, improving cellular metabolic reprogramming (OCR and ECAR), and protecting against lung tissue damage.

Stigmasterol from Coicis Semen ameliorates lung injury in COPD rats by activating PPARγ, which reprograms alveolar macrophage metabolism and drives M2 polarization.

To evaluate the clinical characteristics and their associations with treatment response and prognosis in multiple myeloma (MM) patients with positive autoantibody profiles (PA).

This single-center retrospective cohort study enrolled 189 MM patients who had undergone the autoantibody profile tests at the Gansu Provincial Clinical Medical Research Center for Molecular Diagnosis and Treatment of Hematological Diseases, the First Hospital, Lanzhou University, from April 2015 to April 2025. Follow-up data were collected until August 1, 2025. Based on the autoantibody profile results, patients were categorized into a negative autoantibody profiles group (NA) and a PA group for comparison of baseline characteristics and treatment responses between the two groups. The assessment of treatment response included the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, non-response rate, and the utilization rates of key therapeutic strategies, such as anti-CD38 monoclonal antibody therapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Furthermore, the PA group patients were stratified into three subtypes based on antibody profiles: antinuclear antibody (ANA)-positive, anti-extractable nuclear antigen (ENA) antibody-positive, and antineutrophil cytoplasmic antibody (ANCA)-positive, to analyze prognostic differences. The Kaplan-Meier survival curve was used to calculate median survival time, and Cox regression analysis was performed to evaluate prognostic factors.

A total of 189 patients with MM were included, with 57 (30.16%) in the PA group and 132 (69.84%) in the NA group. All patients received treatment; 58 (30.69%) received anti-CD38 monoclonal antibody therapy, and 57 (30.16%) underwent auto-HSCT. After induction therapy, the ORR was 75.66% (143/189), comprising a PR in 43.39% (82/189) and a CR in 32.28% (61/189). The CR rate was significantly lower in the PA group than in the NA group (21.05% vs 37.12%, P=0.031). At a median follow-up of 39 months (IQR 16 to 59), the median progression-free survival (PFS) was 37 months (IQR 16 to 58) for the entire cohort, while the median overall survival (OS) was not reached. Kaplan-Meier analysis showed significantly shorter median PFS in the PA group versus the NA group (31 vs 43 months, P=0.048). Subgroup analysis based on specific autoantibodies revealed that patients with anti-ENA antibody positivity had significantly shorter median OS (41 vs 61 months, P=0.038) and PFS (28 vs 41 months, P=0.001) than those without. No significant differences in OS or PFS were observed between ANA/ANCA-positive and -negative groups. Cox regression identified anti-ENA antibody positivity (P=0.004) and male sex (P<0.001) as independent risk factors for OS, whereas achievement of CR post-induction (P=0.002) and anti-CD38 therapy (P=0.008) were protective factors. For PFS, independent risk factors were male sex (P<0.001) and anti-ENA positivity (P<0.001), with protective factors including elevated fibrinogen (P=0.011), achievement of CR (P=0.009), and anti-CD38 therapy (P=0.011).

MM patients with positive autoantibodies exhibit inferior responses to induction therapy and poor long-term outcomes. Anti-ENA antibody positivity is an independent risk factor for both OS and PFS in MM.