OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To explore the effects of hydroxychloroquine (HCQ) on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia (AML) and its molecular mechanism. METHODS: Bone marrow or peripheral blood samples of 36 AML patients with severe infection (AML-SI) and 29 AML patients without infection (AML-NI) after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023. In addition, the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group. The mRNA expressions of CXCL12, CXCR4 and CXCR7 were detected by RT-qPCR technology, and the levels of IL-6, IL-8 and TNF-α were detected by ELISA. Leukemia-derived THP-1 cells were selected and constructed as AML disease model. At the same time, bone marrow mesenchymal stem cells (BM-MSCs) from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group. THP-1 cells were treated with different concentration gradients of HCQ. The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry. ELISA was used to detect the changes of IL-6, IL-8 and TNF-α levels in the supernatant of the cell co-culture system, RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis, and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins. RESULTS: CXCL12, CXCR4, CXCR7, as well as IL-6, IL-8, and TNF-α were all abnormally increased in AML patients, and the increases were more significant in AML-SI patients (P <0.01). Furthermore, there were statistically significant differences between AML-NI patients and AML-SI patients (all P <0.05). HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells, but the low concentration of HCQ had no significant effect on the killing of THP-1 cells. When THP-1 cells were co-cultured with BM-MSCs of AML patients, the levels of IL-6, IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group (all P <0.01). After HCQ intervention, the levels of IL-6, IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention (all P <0.01). Similarly, those of Co-culture group were also significantly decreased (all P <0.001). However, the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ. HCQ could up-regulate the expression of pro-apoptotic protein Bax, down-regulate the expression of anti-apoptotic protein Bcl-2, as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κB pathway, then induce the programmed death of THP-1 cells after intervention. CONCLUSION The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients. HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells. The mechanisms may be related to regulating the expression of Bcl-2 family proteins, hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κB signaling pathway.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Hydroxychloroquine/pharmacology* ; Receptors, CXCR4/metabolism* ; Apoptosis/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Chemokine CXCL12/metabolism* ; Interleukin-8/metabolism* ; Interleukin-6/metabolism* ; Receptors, CXCR/metabolism* ; Mesenchymal Stem Cells ; THP-1 Cells

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective To comprehensively excavate and analyze the research status,research hotspots and future trends of the literature related to the field of acupoint catgut embedding therapy for pain treatment in the CNKI database.Methods We searched the CNKI database from its establishment to June 2022,and scientifically analyzed the authors,keywords,and institutions of the included literature of acupoint catgut embedding therapy for pain treatment through specific algorithms of Citespace to generate a visual knowledge map.Results A total of 319 documents were included for statistical analysis,the number of publications in the field of acupoint catgut embedding therapy for the treatment of pain was generally on the rise,the number of publications by various authors was on the low side,and there was a lack of co-operation between the research teams,with the main institutions being the Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Affiliated Hospital of Youjiang Medical Universities of Nationalities and the Guangzhou University of Chinese Medicine,forming a 10-keyword clustering,and the hotspots of diseases under study were mainly mixed haemorrhoids,postoperative pain,low back and leg pain and dysmenorrhoea,etc..The main interventions were pure acupoint catgut embedding therapy and the combination of acupoint catgut embedding therapy and other acupuncture therapies,and the main research method was clinical research.Conclusion Acupoint catgut embedding therapy for the treatment of pain has a good development prospect,the future needs to deepen the clinical research,strengthen the mechanism research,pay attention to the joint use of acupoint catgut embedding therapy and other traditional Chinese medicine methods,and pay attention to the research of different thread materials.

Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency＞100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.

Objective:To investigate the incidence of PTPN11 gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia(AML),and analyze its clinical characteristics.Methods:Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations,and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University,Changzhou Second People's Hospital,Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.Results:Among 451 primary adult AML patients,the PTPN11 gene mutation was detected in 34 cases,and the mutation rate was 7.5％.In the 34 patients,37 PTPN11 alterations were found,which were exclusively missense mutations affecting residues located within the N-SH2(31 cases)and PTP(6 cases)domains and clustered overwhelmingly in exon 3.The platelet count of PTPN11 mutation patients was 76.5(23.5,119.0)× 109/L,which was significantly higher than 41.0(22.0,82.5)×109/L of wild-type patients(P＜0.05).While,there were no significant differences in sex,age,peripheral white blood cell count,hemoglobin,and bone marrow blast between PTPN11 mutation and wild-type patients(P＞0.05).In FAB subtypes,PTPN11 mutations were mainly distributed in M5,followed by M2 and M4,less frequently in M3 and M6.There was no significant difference in the distribution of FAB subtypes between PTPN11 mutation and wild-type patients(P＞0.05).A total of 118 AML patients were detected positive fusion gene,among which patients with PTPN11 mutations had a higher incidence of positive MLL-AF6 than wild-type ones(P＜0.01).97.1％of 34 patients with PTPN11 mutations were accompanied by other mutations,in descending order,they were respectively NPM1(38.2％),NRAS(32.4％),FLT3-ITD(32.4％),DNMT3A(32.4％)and KRAS(23.5％),etc.Conclusion:PTPN11 mutation has a certain incidence in AML patients and is clustered overwhelmingly in exon 3.ALL of them are exclusively missense mutations,and most often present in conjunction with NPM1 mutations.FAB typing of PTPN11 mutation is mostly manifested as M5 subtype,which is associated with higher platelet counts.

AIM To study the phenylpropanoids from Brandisia hancei Hook.f.and their antioxidant activities.METHODS The extract from B.hancei was isolated and purified by Rp-C18,MCI,semi-preparative HPLC,silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The cytotoxicities was determined by MTT method,and the antioxidant activities were determined by DPPH and ABTS+free radical scavenging methods.RESULTS Fifteen phenylpropanoids were isolated and identified as(+)-pinonesinol(1),(-)-medioresinol(2),(-)-syringaresinol(3),buddlenol D(4),(7R,7'R,7″S,8S,8'S,8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol(5),(-)-(7R,7'R,7″R,8S,8'S,8″S)-4',4″-dihydroxy-3,3',3″,5-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineolignan-7″,9″-diol(6),hedyotol A(7),dracunculifoside R(8),acteoside(9),isoacteoside(10),arenarioside(11),isomartynoside(12),curcasinlignan B(13),erythro-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-l-ol(14),citrusin C(15).Compounds 1-4 and 9-10 had no obvious cytotoxicity to HepG2 hepatoma cells.Compounds 1,3,9,10 and 12 had strong scavenging activities against DPPH radicals.Compounds 1-3,9-10,12 and 14 showed strong scavenging activities against ABTS+radical.CONCLUSION Compounds 1-8 and 12-15 are isolated from genus Brandisia for the first time.The phenylpropanoids from B.hancei show strong antioxidant activities.

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.

Objective To investigate the anti-atherosclerotic mechanism of herbal cake-separated moxibustion.Methods Twenty-four New Zealand purebred male rabbits were randomly divided into normal group,model group,herbal cake-separated moxibustion group and Atorvastatin group,with 6 rabbits in each group.Except for the normal group,the rabbits in the other groups were fed with high-fat diet mixed with Propylthiouracil(PTU)method to construct an atherosclerosis model.At the same period of modeling,corresponding intervention was given.After 12 weeks,the levels of serum total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)were detected.The pathological changes of rabbit aortic tissue were observed by hematoxylin-eosin(HE)staining.The levels of serum tumor necrosis factor α(TNF-α),interleukin 6(IL-6)and interleukin 10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA).The contents of phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)in myocardial tissue were detected by Western Blot.Results Compared with the normal group,the serum levels of TC,TG and LDL-C in the model group were significantly increased(P＜0.001),the aortic vascular endothelial structure was significantly damaged,the serum levels of TNF-α and IL-6 were increased(P＜0.001),the serum level of IL-10 was decreased(P＜0.01),and the protein expression levels of PI3K,p-AKT and p-mTOR in myocardial tissue were significantly decreased(P＜0.05 or P＜0.01).Compared with the model group,the above indexes in the herbal cake-separated moxibustion group and the Atorvastatin group were significantly improved(P＜0.05 or P＜0.01 or P＜0.001).Compared with the Atorvastatin group,the contents of TG and LDL-C in the herbal cake-separated moxibustion group were increased(P＜0.01),and other indicators did not change significantly(P＞0.05).Conclusion The mechanism of anti-atherosclerosis of herbal cake-separated moxibustion may be related to the activation of PI3K/AKT/mTOR signaling pathway and the regulation of the expressions of inflammatory mediators TNF-α,IL-6 and IL-10.

Objective To retrospectively analyze the clinical data of skin ulcer patients in Lingnan area,and to explore the distribution of traditional Chinese medicine(TCM)syndrome types and their related influencing factors.Methods The clinical data of 241 patients with skin ulcer who were hospitalized in the Department of Dermatology,Guangdong Provincial Hospital of Chinese Medicine from August 2012 to July 2022 were collected,and their clinical characteristics and distribution of TCM syndrome types were analyzed.Results(1)The analysis of clinical characteristics showed that the age of the 241 patients with skin ulcers ranged from 10 years old to 98 years old,and the patients aged 70-79 years had the high incidence;the course of disease ranged from one week to more than 20 years,and most of the patients had the course of disease being 1-5 year(s);most of the patients were male,and the ratio of male to female was 1.62∶1;a total of 200 cases(82.99%)suffered skin ulcers in the lower limbs,17 cases(7.05%)suffered skin ulcers in the trunk,13 cases(5.39%)suffered multiple skin ulcers in the whole body,9 cases(3.73%)suffered skin ulcers in the upper limbs,and 2 cases(0.83%)suffered skin ulcers in the head and face.There was no significant difference in the gender and foci of the patients(P＞0.05).(2)The distribution of TCM syndrome types showed that among the 241 patients with skin ulcers,damp-heat and stasis obstruction syndrome was the most common(46.89%),followed by spleen deficiency with predominant dampness syndrome(27.39%),qi deficiency and blood stasis syndrome(14.11%),and qi and yin deficiency syndrome(11.62%).There was no significant difference in the gender among the four TCM syndrome types(P＞0.05),but there was significant difference in the age of the patients(P＜0.05).Conclusion There were certain differences exert in the distribution of the age,gender,foci and course of disease in the patients with skin ulcers in Lingnan area,and the damp-heat and stasis obstruction syndrome is the most common type of the patients.