ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Background Adverse drug reactions (ADRs) to sodium dimercaptosulphonate (DMPS) mercury removal treatment have been reported in occupational mercury poisoning. In recent years, the number of cases of mercury poisoning due to mercury-containing cosmetics has been increasing, and ADRs to the use of DMPS are common in clinical practice. Objective To investigate the occurrence of ADRs and the influencing factors in patients with chronic mercury poisoning and mercury exposure treated with DMPS for mercury removal. Methods Patients treated with DMPS due to mercury poisoning at the Occupational Disease Department of Nanjing Prevention and Treatment Center for Occupational Diseases from June 2017 to December 2023 were included in the study. Information on demographics, baseline characteristics, and treatment regimens was collected at admission. Information on secondhand smoke, place of residence, and blood groups not collected at admission was collected in follow-up. The patients were divided into two groups according to whether ADRs occurred after the use of DMPS and were compared for clinical characteristics, and the influencing factors related to the occurrence of ADRs after DMPS treatment were analyzed by binary logistic regression. Results A total of 72 patients were enrolled in the study, of which 26 reported ADRs during mercury removal. A total of 29 ADRs occurred, mainly rash in 11 cases (37.9%), fever in 5 cases (17.2%), and nausea in 4 cases (13.8%). Most ADRs occurred in the second course (7 cases, 26.9%) and the third course (9 cases, 34.6%). Of the 22 non-menopausal women who experienced ADRs, 13 (59.1%) used DMPS in the week prior to menstruation. The logistic regression analysis showed that smoking (OR=27.911, 95%CI: 2.835, 725.809) and blood type O (OR=6.885, 95%CI: 2.014, 26.896) were associated with elevated occurrence of ADRs after DMPS treatment. Conclusions The probability of ADRs after DMPS treatment is not low, but mild presentations are predominant and resolved with immediate treatment, with a favourable prognosis. The O blood group, smoking individuals, and female patients using DMPS one week before menstruation may be more prone to ADRs.

Objectives:To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed.Results:Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed.Conclusions:When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.

A retrospective analysis was conducted on three patients with primary myelofibrosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from 2020 to 2023. They subsequently developed poor graft function. The patients received selected donor CD34 + cell boosts as salvage therapy. There were two male patients and one female patient, with a median age of 68 (39-69) years. The median time from allo-HSCT to the selected donor CD34 + cell boost was 83 (56-154) days. The median infusion of selected donor CD34 + cells was 7.67 (7.61-9.06) ×10 6/kg, with a CD34 + cell purity of 97.76% (96.50%-97.91%) and a recovery rate of 70% (42%-75%) . Hematological recovery was achieved in two cases. No acute GVHD was observed in any of the three patients. One case of moderate oral chronic GVHD was noted. Selected donor CD34 + cell boosts for the treatment of poor graft function after allo-HSCT in primary myelofibrosis was effective and no severe acute or chronic GVHD was observed.

Objective:To explore the clinical features, treatment and prognosis of refractory hyponatremia caused by secondary adrenal cortical insufficiency (SACI) after chemotherapy in children with tumors of the lymphoid hematopoietic system.Methods:Clinical data including age, sex, serum sodium level, time of onset of hyponatremia, duration of hyponatremia, cortisol level, 24 h urinary sodium level, plasma/urine osmotic pressure, treatment and prognosis of 3 acute lymphoblastic leukemia (ALL) children and 1 lymphoblastic lymphoma (LBL) child with SACI-caused refractory hyponatremia treated at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were analyzed retrospectively.Results:The 4 patients were all boys, and they received Dexamethasone chemotherapy.The primary clinical manifestations were fatigue, moderate hyponatremia in 3 cases, and mild hyponatremia in 1 case.Hyponatremia occurred after 1 week of glucocorticoid therapy and persisted for 10-20 days (mean 14.25 days).The 24 h urinary sodium level increased, plasma osmotic pressure slightly decreased or was at the low limit of the normal range, and urine osmotic pressure was greater than plasma osmotic pressure.The serum cortisol level at 8∶00 AM.decreased in 1 LBL case, increased in 1 ALL case, and remained normal in 2 ALL cases.After treatment with Hydrocortisone [10 mg/(m 2·d), taken orally in 2 doses], hyponatremia was quickly corrected within 3-5 days. Conclusions:When receiving glucocorticoid therapy, children with tumors of the lymphoid hematopoietic system may have SACI, and the hyponatremia caused by it generally appears 1 week after glucocorticoid therapy and persists for a long time.Laboratory tests are similar to the syndrome of inappropriate antidiuretic hormone secretion, but the response to intravenous/oral supplementation of concentrated sodium and water restriction treatment is poor.The addition of Hydrocortisone can quickly correct hyponatremia, and the prognosis is excellent.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Objective To construct the triple pre-rehabilitation program for the patients undergoing pancreaticoduodenectomy to provide a theoretical basis for the preoperative management of this operation mode.Methods The raft plan was formed by the literature research and group discussion,then the experts were invited to conduct the two rounds of expert consultation,and the final draft of the plan was finally formed.Results The draft plan included the 3 first-level items,9 second-level items and 28 third-level items.The questionnaire recovery rate of the two rounds of expert correspondence was 100%,and the authority coef-ficients were 0.88 and 0.93,respectively.The mean importance and feasibility scores of each item in the two rounds of expert consultation were ≥3.5,and the coefficient of variation was<0.25.The first draft of the final formation plan included the 3 first-level items,9 second-level items and 31 third-level items.Conclusion This program has ne-cessity,scientificity and feasibility.Clarifying the specific contents and scope of preoperative management of this operation mode could provide a theoretical basis for medical staff to carry out pre-rehabilitation.

Background and purpose:Colorectal carcinoma(CRC)is a common malignant tumor with incidence and mortality rates second only to gastric cancer and esophageal cancer among digestive system malignancies.Increasing evidence suggests that immune cells play a significant role in the occurrence and development of CRC.The aim of this study was to construct a prognostic model related to immune cell-associated genes to predict the prognosis of CRC patients and enable precise management.Methods:Single-cell RNA sequencing(scRNA-seq)and bulk RNA sequencing(RNA-seq)data,along with clinical information for colorectal cancer,were downloaded from the Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)databases.Differential genes of immune cell subtypes were extracted,and genes related to prognosis were screened in TCGA data using Cox regression and LASSO regression,with external validation using GSE39582 and GSE41258.The prognostic model was used to analyze chemotherapy drug sensitivity,assess immunotherapy efficacy,analyze pathways related to risk scores,and perform clinical correlation analysis.Finally,the expression levels of model genes were validated in 10 fresh frozen CRC tissues with post-operative pathological examination and cell lines using real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and immunohistochemistry.All samples were approved by the Fudan University Shanghai Cancer Center Ethics Committee(No.050432-4-2108*).Results:We defined 16 cell clusters based on the scRNA-seq dataset(GSE161277)and labeled these clusters as different cell types using the R package celldex.Differential analysis of immune cell subtypes yielded 374 differentially expressed genes.Using univariate Cox and LASSO analyses,we constructed a 9-gene risk prognostic model in CRC.This risk model exhibited reliable prognostic prediction performance and played an important role in predicting anti-tumor drug sensitivity,immunotherapy efficacy,potential molecular mechanisms,and clinical characteristics.Patients with high-risk scores had a lower probability of benefiting from immunotherapy.Conclusion:We constructed a 9-gene risk prognostic model based on the heterogeneity of immune cells in the CRC tumor microenvironment,which predicted the survival and treatment outcomes of CRC patients.