In March 2024, three male and two female specimens of the genus Lispe were intercepted on cargo ships inbound for Wan Zai Port under Gongbei Customs. Based on morphological characteristics and molecular analysis, the specimens were identified as Lispe pumila. In this study, we describe the morphological features, diagnostic characteristics, and geographical distribution of L. pumila, with the aim of providing a reference for the identification of this species when intercepted at ports.

Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

BackgroundSuicide and self-injury risk in patients with depression disorder is associated with pain symptoms， but the relationships between specific pain types and their severity and distinct self-injury/suicide risk phenotypes remain controversial. ObjectiveTo explore whether somatic pain can reflect different self-injury/suicide risk phenotypes， and to provide references for the clinical identification of suicide and self-injury risk in patients with depression. MethodsBased on data from the National Survey on Symptomatology of Depression （NSSD）， 3 275 patients who met the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fourth edition， text revision （DSM-IV-TR） were recruited. According to previous suicidal behavior， suicidal ideation and self-injury behavior in the past two weeks， patients were divided into the no self-injury/suicide risk group， self-injury group， and high suicide-risk group. The occurrence of headache， muscle soreness， trunk pain， limb pain， and other pain symptoms was assessed using the structured symptom assessment instrument of the NSSD. With the no self-injury/suicide risk group as the reference， an ordinal Logistic regression model was used to analyze the associations between the risk groups and the occurrence frequency of pain， with demographic and clinical characteristics entered into the model as covariates for adjustment. ResultsA total of 3 211 patients （98.05%） were included in the analysis， including 1 329 cases （41.39%） in the no self-injury/suicide risk group， 415 cases （12.92%） in the self-injury group， and 1 467 cases （45.69%） in the high suicide-risk group. Compared with the no self-injury/suicide risk group， the occurrence frequencies of headache （OR=1.526， 95% CI： 1.221–1.894） and muscle soreness （OR=1.287， 95% CI： 1.034–1.597） were higher in the self-injury group， and the occurrence frequencies of headache （OR=0.583， 95% CI： 0.504–0.672）， muscle soreness （OR=0.682， 95% CI： 0.597–0.780）， trunk pain （OR=0.557， 95% CI： 0.475–0.634）， limb pain （OR=0.454， 95% CI： 0.384–0.522）， and other pain difficult to localize （OR=0.542， 95% CI： 0.472–0.631） were all lower in the high suicide-risk group. ConclusionPatients with depression disorder across different self-injury and suicide risk phenotypes exhibit distinct pain characteristics， and these differences may provide a reference for the clinical identification of suicide and self-injury risk in patients with depression disorder. ［Funded by The National Key Research and Development Program of China during the "13th Five-Year Plan" period （number， 2016YFC1307100）； Shanghai Key Clinical Specialties Construction Project］

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.