Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.

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.

Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Objective:To investigate the relationship between rs2075748 and rs542269 single nucleotide polymorphisms of cholinergic muscarinic receptor 1 (CHRM1)gene and susceptibility of childhood asthma, as well as the differences of pulmonary function and serum acetylcholine(Ach)levels among different genotypes.Methods:A total of 156 asthmatic children who were treated in the outpatient or hospitalized in the General Hospital of the Northern Theater Command from September 2018 to September 2020 were selected as the case group, while 134 non-asthmatic children who had a healthy physical examination were selected as the control group.The SNaPshot SNP typing technique was used to analyze the genotype of the CHRM1 gene rs2075748 and rs542269 of the study subjects.Serum Ach level was detected by double antibody sandwich method, and the pulmonary function of the case group was detected.Results:After analyzing the CHRM1 gene polymorphism, it was found that the CC, CT, and TT genotype frequencies at rs2075748 were 65.4%, 28.8%, 5.8% in the case group, and 62.8%, 32.4%, 4.8% in the control group.The C and T allele frequencies were 79.8% and 20.2% in the case group, 74.3% and 25.7% in the control group.There were no significant difference in the genotype and allele frequency distribution between the two group ( χ2=2.688, 2.530, both P>0.05), and there were no significant difference in the recessive and dominant modes between the two groups ( χ2=0.338, 2.686, both P>0.05). The TT and CT genotype frequencies at rs542269 locus were 72.4% and 27.6% in the case group, 62.7% and 37.3% in the control group.The T and C allele frequency were 86.2% and 13.8% in the case group, 81.3% and 18.7% in the control group.The genotype and allele frequency distribution were not obvious different between the two group ( χ2=3.145, 2.544, both P>0.05). The risk of asthma with variant CT and TT at rs2075748 locus of CHRM1 gene were not statistically different from that of wild-type CC (both P>0.05), and the risk of asthma with variant CT at rs542269 locus was no different from that of wild-type TT ( P>0.05). The difference in FEF50% Pred and FEF75% Pred of different genotypes at rs2075748 were statistically significant( F=3.118, 4.808, both P<0.05), wild-type CC was lower than variant CT(both P<0.05). There were no statistically significant difference in pulmonary function among different genotypes at rs542269 (both P>0.05). There was significant difference in serum Ach level between different genotypes of rs2075748 ( F=4.716, P<0.05), variant CT was lower than wild-type CC ( P<0.05), variant TT was lower than wild-type CC ( P<0.05), while no significant difference was find between variant CT and TT ( P>0.05). There was no significant difference in serum Ach level between different genotypes of rs542269 ( P>0.05). Conclusion:The rs2075748 locus of CHRM1 gene is not susceptible to asthma, but it may be related to the small airway function of asthmatic children, besides there are differences in serum Ach levels with different genotypes, and the variant serum Ach level is lower.The rs542269 locus is not a susceptibility site for asthma, and there are no difference in pulmonary function and serum Ach levels in asthmatic children with different genotypes.

Objective:To investigate the correlation between single nucleotide polymorphism of corticosteroids receptor gene(NR3C1)and children with asthma and to analyze the efficacy of inhaled corticosteroid(ICS)treatment.Methods:The study included a control group(100 healthy children)who participated in the physical examination and an asthma group(101 children with bronchial asthma)who were hospitalized in the General Hospital of the Northern Theater Command from October 2018 to October 2020.Genomic DNA was extracted from peripheral blood samples of all enrolled subjects and then the polymorphism of the glucocorticoid receptor gene locus of NR3C1 was analyzed using SNaPshot SNP gene detection technology.The comparisons of allele frequency in rs41423247、rs7701443 between two groups were performed and the treatment effects of ICS in the asthma group were evaluated at the 12th week of treatment.Results:The frequencies of GG, GC, and CC genotypes of rs41423247 locus of NR3C1 were 75.2%, 21.8%, and 3.0% in the asthma group and 72.0%, 24.0%, and 4.0% in the control group, respectively, and there were no statistically significant differences between the two groups( χ2=0.333, P>0.05). The frequencies of GG, GA, and AA genotypes of rs7701443 locus of NR3C1 were 45.5%, 39.6%, and 14.9% in the asthma group and 56.0%, 31.0%, and 13.0% in the control group, respectively, and there were no statistically significant differences between the two groups( χ2=2.259, P>0.05). After ICS treatment, the C-ACT/ACT scores were not significantly improved in children with CC genotypes at rs41423247 locus( P>0.05), while children with GG and GC genotypes were obviously improved( P<0.05). The scores of C-ACT/ACT showed obvious differences among three genotypes of rs41423247 locus after treatment with ICS( P<0.05). The C-ACT/ACT scores of all were significantly improved in children with GG, GA, or AA genotypes at rs7701443 locus after treatment with ICS( P<0.05), while there was no significant difference among those three genotypes( P>0.05). Significantly improved pulmonary function following ICS treatment in children with asthma was observed in GG and GC genotypes of rs41423247 locus of NR3C1( P<0.05), while only MMEF was improved in CC genotype( P<0.05). Meanwhile, those pulmonary function indexes were improved in all genotypes of rs7701443 after treatment with ICS( P<0.05). Conclusion:Both rs41423247 and rs7701443 locus at NR3C1 gene have polymorphisms.But there were no significant differences in the polymorphism of rs41423247 and rs7701443 locus of NR3C1 between the asthma group and the control group.Different genotype frequencies of rs41423247 and rs7701443 at NR3C1 locus in children with asthma have different effects on ICS treatment.

Objective To detect the expression of β-catenin in the tissues of primary central nervous system lymphoma (PCNSL), and to discuss its function in PCNSL.Methods The paraffin embedded tissues from 10 patients diagnosed as PCNSL from October 2010 to April 2012 were collected as the experimental group.The paraffin embedded tissues from 10 patients with lymphadenitis were collected as the control group.Quantitative real-time PCR and immunohistochemical method were used to detect the expression of β-catenin in these tissues, and the relationships between β-catenin and clinical data were analyzed.Results Immunohistochemistry results showed that β-catenin protein was localized in the cytoplasm and (or) nucleus.Among 10 PCNSL patients, β-catenin protein was positive in 4 patients, while it was no positive in all of 10 lymphadenitis patients, with the significant differences between both groups (P ＜ 0.05).The β-catenin gene relative expression level was 4.70±0.57 and 1.00±0.27 in the experimental group and the control group, respectively.β-catenin expression was no correlation to age, PS score, cerebrospinal fluid protein level and serum lactate dehydrogenase level of patients with PCNSL.Conclusions Whether in mRNA level or in protein level, β-catenin expression is always high in PCNSL tissues, and its protein is expressed in the cytoplasm, however, this phenomenon was not observed in the tissue of lymphadenitis.