Objective To investigate the relationship between pre-liver transplantation plasma soluble programmed cell death protein 1 (sPD-1) levels and prognosis in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICI). Methods A total of 38 HCC liver transplant recipients who received ICI treatment at Beijing Tsinghua Changgung Hospital from January 2021 to February 2024 were included in the study. The use of ICI drugs was reviewed, and the clinical and pathological characteristics of patients with and without postoperative HCC recurrence were compared. Kaplan-Meier analysis was used to evaluate postoperative survival. Pre-transplant plasma samples were collected from patients treated with ICI, and the sPD-1 levels were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic curves were plotted to explore the relationship between sPD-1 expression and clinical pathological features and to analyze the prognosis. The effects of different preoperative ICI discontinuation times on sPD-1 expression were also compared. Results Among the patients, 28 (74%) received anti-programmed cell death protein 1 (PD-1) monoclonal antibodies, 9 (24%) received anti-programmed cell death protein ligand 1 (PD-L1) monoclonal antibodies, and 1 (3%) received bispecific antibodies. Patients were grouped based on whether they had HCC recurrence within 1 year after surgery. Significant differences were found between the two groups in preoperative alpha-fetoprotein levels, tumor number, maximum tumor diameter, capsular invasion, differentiation grade, Ki67 index, conform to Milan criteria, conform to University of California at San Francisco (UCSF) criteria and tumor, node, metastasis (TNM) staging (all P<0.05). The median pre-transplant plasma sPD-1 level was 902 (318, 4 406) pg/mL, and the sPD-1 level was higher in the recurrence group than in the non-recurrence group (P<0.05). Using 2 073 pg/mL as the cut-off value, patients were divided into high and low sPD-1 level groups. Significant differences were found between the two groups in tumor number, postoperative hospital stay and total hospital stay (all P<0.05). Kaplan-Meier analysis showed that the disease-free survival rate was lower in the high sPD-1 level group than in the low sPD-1 level group (P=0.004), while the overall survival rate did not differ significantly between the two groups (P=0.381). In addition, patients who discontinued ICI treatment ≤ 5 half-lives before surgery had higher sPD-1 levels than those who discontinued ICI treatment for >5 half-lives before surgery. Conclusions Pre-transplant plasma sPD-1 levels are closely related to prognosis and may reflect the dynamic changes in the immune microenvironment. For patients with high pre-transplant plasma sPD-1 levels, the indications for liver transplantation should be carefully evaluated, and postoperative management and follow-up should be strengthened. Early intervention should be provided to improve patients' quality of life and prolong their survival.

OBJECTIVE: To investigate the predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL). METHODS: A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment. RESULTS: A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group. CONCLUSION At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans ; Lymphoma, Mantle-Cell/pathology* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; ROC Curve

OBJECTIVE: To investigate the predictive role of the modified Endothelial Activation and Stress Index (mEASIX) in the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy and cytokine release syndrome (CRS). METHODS: The clinical data of 70 relapsed and refractory (R/R) B-cell tumor patients who were treated with CAR-T therapy from September 1, 2018 to February 28, 2023 in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were retrospectively analyzed. The value of log-2 mEASIX before conditioning (-7 d) was calculated, and the patients were divided into a low-mEASIX group (42 patients) and a high-mEASIX group (28 patients) based on the cut-off value of 5.443 determined by the receiver operating characteristic (ROC) curve. Eventually, the predictive role of mEASIX before conditioning on the efficacy of CAR-T cell therapy and CRS was analyzed. RESULTS: The high-mEASIX group exhibited significantly worse median overall survival (OS) and median progression-free survival (PFS) in comparison to the low mEASIX group (OS: 3.2 months vs not reached, P < 0.01; PFS: 1.3 months vs 6.0 months, P =0.009). The incidence of grade ≥2 CRS in the high-mEASIX group was substantially higher than that in the low-mEASIX group (57.1% vs 19.0%, P =0.007). The degree of remission after CAR-T therapy (P =0.001), whether CRS occurs or not (P =0.041), the lactate dehydrogenase (LDH) level before conditioning (P =0.046), and the mEASIX score before conditioning (P =0.047) were independent influencing factors for the OS of patients receiving CAR-T cell therapy. CONCLUSION The mEASIX score before conditioning can predict OS and the incidence of grade ≥2 CRS in patients with relapsed and refractory B-cell tumors who receive CAR-T cell therapy.
Cytokine Release Syndrome/therapy* ; Immunotherapy, Adoptive/methods* ; Humans ; Lymphoma, B-Cell/therapy* ; Retrospective Studies ; Hematology ; China ; Receptors, Chimeric Antigen/blood* ; Predictive Value of Tests

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

The pre-research of medical device standards is of great significance for the enactment and amendment of standards.This study discusses four aspects and explores how to promote more scientific and reasonable pre-research.Based on the pre-research practice of medical device standards project,this study puts forward relevant work ideas and suggestions.

Objective To analyze the clinical outcomes of extended thymectomy for myasthenia gravis (MG) patients under different surgical approaches, and to determine the factors affecting the prognosis of MG. Methods The MG patients who underwent extended thymectomy from January 2014 to March 2021 in our hospital were retrospectively collected. According to the surgical approach, they were divided into a subxiphoid group and an intercostal group, and the perioperative results and prognosis were compared between the two groups. A “good outcome” was defined as complete stable remission (CSR), pharmacological remission (PR) or minimal manifestations state (MMS); a “poor outcome” was defined as outcomes worse than MMS. Univariate and multivariate logistic regression analyses were performed to assess the factors associated with the good outcomes. Results A total of 187 MG patients were included in the study, including 82 males and 105 females, with a median age of 50 (36, 60) years. There were 134 patients in the intercostal group and 53 patients in the subxiphoid group. Compared with the intercostal group, although the operation time of the subxiphoid group was longer [200.0 (172.0, 232.0) min vs. 141.0 (118.0, 169.0) min, P<0.001], the intraoperative blood loss was less [10.0 (10.0, 20.0) mL vs. 20.0 (10.0, 50.0) mL, P<0.001], the postoperative hospital stay was shorter [3.0 (2.5, 4.0) d vs. 5.0 (3.0, 7.0) d, P<0.001], and the incidence of complications was lower [1 (1.9%) vs. 26 (19.4%), P=0.001]. A total of 159 (85.0%) patients were followed up for a median period of 46 (13, 99) months, with a good outcome rate of 90.6% and CSR rate of 33.3%. There were no statistical differences in PR, MMS or overall good outcome rates between the two groups (P>0.05). Multivariate logistic analysis showed that age≤50 years was an independent predictor for "good outcome" of MG patients. Conclusion Extended thymectomy via subxiphoid for MG is a safe, feasible and effective surgical approach.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.