This study was purposed to investigate the immune reconstitution of T-cells in patients who received haploidentical hematopoietic stem cell transplantation (hiHSCT). The peripheral blood was harvested from 22 patients before transplantation and at month 1, 3, 6 after hiHSCT. The proportions of T lymphocyte subtypes including CD3(+), CD4(+), CD8(+), CD45RO(+), and CD45RA(+)CD62L(+) were analyzed by flow cytometry, followed by the calculation of T cell numbers according to the amounts of peripheral blood leukocytes. Adenosine triphosphate (ATP) value in CD4(+) T cells was measured by ImmuKnow method to evaluate the function of lymphocytes. The results showed that the CD3(+) cell absolute value before transplantation was 833.75 ± 359.84/µl, but those values at month 1, 3, 6 after transplantation were 318.87 ± 266.71/µl, 1006.76 ± 512.32/µl and 1296.38 ± 958.77/µl respectively. The CD4(+) cell absolute value before transplantation was 336.99 ± 211.11/µl, but such values at month 1, 3, 6 after transplantation were 45.89 ± 44.21/µl, 142.97 ± 114.85/µl, and 181.78 ± 120.61/µl respectively. The CD8(+) cell absolute value before transplantation was 430.21 ± 159.48/µl, but those values at month 1, 3, 6 after transplantation were 230.44 ± 195.89/µl, 621.64 ± 318.83/µl, and 823.07 ± 633.55/µl respectively. The CD4(+)CD45RO(+) memory T cell absolute value before transplantation was 227.44 ± 73.34/µl, but such values at month 1, 3, 6 after transplantation were 43.47 ± 43.40/µl, 138.69 ± 110.17/µl, 147.73 ± 82.94/µl respectively. The CD8(+)CD45RO(+) memory T cell absolute value before transplantation was 212.70 ± 98.48/µl, but such values at month 1, 3, 6 after transplantation were 184.76 ± 168.65/µl, 445.90 ± 252.50/µl, 519.80 ± 475.53/µl respectively. CD4(+)CD45RA(+)CD62L(+) naive T cell number before transplantation was 68.94 ± 59.74/µl, but such cell numbers at month 1, 3, 6 after transplantation decreased to 2.44 ± 2.93/µl, 3.14 ± 3.48/µl, 23.22 ± 38.38/µl respectively. The CD8(+)CD45RA(+)CD62L(+) naive T cell absolute value before transplantation was 124.82 ± 60.95/µl, but those values at month 1, 3, 6 decreased to 19.37 ± 17.71/µl, 76.63 ± 50.85/µl, and 114.49 ± 174.29/µl respectively. The ATP value in CD4(+) T cells decreased to 210.19 ± 119.37 ng/ml at month 1 after transplantation and increased to 280.62 ± 110.03 ng/ml at month 3, and 357.28 ± 76.18 ng/ml at month 6 after transplantation. It is concluded that CD8(+) memory T cell reconstruction contributes critically to T cell recovery early after hiHSCT, while the thymic output function remains low. However, T cell function recovers to normal range at month 3 after transplantation.
Adolescent ; Adult ; CD8-Positive T-Lymphocytes ; cytology ; Child ; Child, Preschool ; Female ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunophenotyping ; Killer Cells, Natural ; immunology ; Lymphocyte Count ; Male ; T-Lymphocyte Subsets ; immunology ; Young Adult

This study was purposed to investigate the immune state of the patients suffered from pulmonary infection within 6 months after haploidentical hematopoietic stem cell transplantation (hi-HSCT). Adenosine triphosphate (ATP) value in CD4(+) T cells was measured by ImmuKnow method to assess the function of the lymphocytes in peripheral blood of 25 patients at 6 months after hi-HSCT. The results showed that the ATP level in CD4(+) T cells of the patients suffered from pulmonary infection was (179.88 ± 65.41) ng/ml before transplantation, (172.69 ± 118.81) ng/ml at 1 month, (218.15 ± 124.26) ng/ml at 3 months, (313.42 ± 116.29) ng/ml at 6 months after transplantation. The ATP level in CD4(+) T cells of the patients without pulmonary infection was (210.44 ± 94.71) ng/ml before transplantation, and decreased to (193.66 ± 133.69) ng/ml at 1 month and increased gradually to (355.02 ± 43.38) ng/ml at 3 months, (355.73 ± 93.85) ng/ml at 6 months after transplantation. It is concluded that the low ATP value in CD4(+) T cells in patients prior and post hi-HSCT may suggest probability of occurrence for infections, ATP value in CD4(+) T cells may be used as a reference indicator for clinical empirical use of antibiotics.
Adenosine Triphosphate ; analysis ; Adolescent ; Adult ; CD4-Positive T-Lymphocytes ; immunology ; metabolism ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Pneumonia ; immunology ; pathology ; Young Adult

This study was aimed at understanding the trends in,and scope of,severe fever with thrombocytopenia syndrome(SFTS)in Nanjing,analyzing the spatial distribution pattern,detecting high incidence cluster areas and key popula-tions,and scientifically guiding prevention and control strategies and measures.We obtained data on SFTS cases from 2010 to 2023 in Nanjing from the China Disease Control and Prevention Information System,and described the time,popu-lation,and spatial distribution characteristics.We used joinpoint regression to calculate the annual percentage change(APC)in incidence,then used FleXScan spatial clustering scan analysis to explore spatial clustering areas at the street level.A total of 507 SFTS cases were reported from 2010 to 2023 in Nanjing.The APC was 31.8％(95％CI:22.5％-41.9％,P＜0.001),and the reported incidence in 2023 was 1.42/100 000(134 cases).The seasonal indices from May to August were 2.7,2.1,3.0,and 1.3,respectively,accounting for 76.1％of the total cases.The median age was 66(IQR:55,73)years,which gradually increased from 59 years in 2010-2011 to 68 in 2022-2023(P＜0.001);94.1％of cases were in individuals 45 years or older.Farmers,homemakers/unemployed individuals,and retirees accounted for 90.1％.The epidemic area increased from 11 streets in four districts in 2010-2011 to 58 streets in 11 dis-tricts in 2022-2023.Except for 2012-2013,global spatial autocorrelation analysis showed positive Moran's I values(0.224-0.526,P＜0.001),and FlexScan scan indicated that several streets in Lishui District and Jiangning District were the most likely clusters.Four streets in Pukou District were the secondary clusters from 2018 to 2023,and three streets in Luhe District in 2022-2023 were the secondary clusters(all P＜0.05).The reported incidence of SFTS in Nanjing showed a rapid upward trend,with spread of epidemic areas.The spatial distribution pattern was clustered.Strengthened training in diagnosis and treatment technology and detection ability of medical institutions,surveillance in high-incidence areas,tracing of case flow,and health education of tick and disease prevention knowledge are recommended.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

OBJECTIVETo evaluate the safety and effectiveness of a novel therapeutic regimen for bronchiolitis obliterans sydrome (BOS) affter hematopoietic stem cell transplantation (HSCT).

METHODSSeven patients who had received HSCT and had been diagnosed as BOS were enrolled in this study. They received weekly intravenous injection of umbilical cord-derived mesenchymal stem cells (MSC) at a dose of 1 × 10(6)/kg for 4 weeks. Budesonide was given orally at a daily dose of 0.25 g, and salmeterol was inhaled at a dose of 4.5 µg for 3 times per day. Methylprednisolone was given at a dose of 1 mg/(kg·d) for 2 weeks when respiratory failure occured. The dose of methylprednisolone was tapered to 0.25 mg/(kg·d) after 4 weeks and was adjusted according to the occurrence and severity of chronic graft-versus-host disease (cGVHD).

RESULTSThe therapy was generally safe and no severe acute toxicity was observed. One patient died of heart failure during the treatment, the other 6 patients were alive and the pulmonary function parameters including FEV1, FEV1/FVC, PaO2 and AaDO2 were significantly improved after 6 months as compared with the baseline parameters (P < 0.05).

CONCLUSIONMSC combined with budesonide, almeterol and azithromycin has been confirmed to be generally safe and can reduce the dose of glucocorticoid in treatment of BOS after HSCT.

Azithromycin ; therapeutic use ; Bronchiolitis Obliterans ; therapy ; Budesonide ; therapeutic use ; Combined Modality Therapy ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Mesenchymal Stem Cell Transplantation ; Methylprednisolone ; administration & dosage ; therapeutic use ; Salmeterol Xinafoate ; therapeutic use

OBJECTIVE: To observe the safety of donor NK cell infusions in the settings of hematopoietic stem cell transplantation and after consolidation chemotherapy in elderly patients with acute myeloid leukemia (AML). METHODS: Forty patients with AML were included, in which 21 patients aged over 60 years were at the stage of complete remission (CR) and 19 patients that received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononucleated cells were isolated from peripheral blood from the donors (for allo-HSCT) or healthy immediate family members (elderly AML). The cells were seeded into the flasks pre-coated with NK cell specific activators, and expanded in media containing recombinant human IL-15 and IL-2 for 14 days. The cells were transfused intravenously after the identification of quality control. Trypan blue exclusion test was used for the determination of cell viability and counting. Flow cytometry analysis was performed to assess the surface antigenic profile. Seventy-eight infusions of the cell products were received by the elderly patients with AML after consolidation chemotherapy, 11 infusions were received by the patients during allo-HSCT and 32 infusions 3 moths after transplantation. The safety of cell therapy, body temperature, blood pressure and other indexes were observe during and 48 hours after cell transfusion. Meanwhile, the occurrence and severity of acute graft-versus-host disease (GVHD) were documented. RESULTS: Flow cytometry analysis showed that the proportion of NK cells (CD3^-CD56⁺) in the mononucleated cells before culture was (14.10±4.22)% (n=121), and the proportion increased dramatically up to (87.29±8.75)% (n=121) after culture for 14 days, the number of NK cells increased to 753.47±140.13 times (n=121). The doses of the infused NK cells was (7.58±2.50)×10⁷/kg per infusion. Moderate fever occurred in three cases after multiple infusions, and the temperature restored to normal on the same day after treatment. Fever was observed in one patient after every infusion of four times in total. The temperature reached to 38.5-39.0 ℃ and returned to normal within 1-2 hours after adequate antipyretic treatment, and then there was no discomfort. No GVHD was observed in the elderly AML patients, while 6 cases that received allo-HSCT developed moderate acute GVHD, among them grade I in 5 cases and grade II in 1 case. No other severe toxicities were observed. CONCLUSION NK cell products with a high-purity could be obtained by ex vivo expansion with this protocol. The transfusion of these expanded cells is generally safe in the elderly patients with AML that have received chemotherapy or patients that received hematopoietic stem cell transplantation.
Aged ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/therapy* ; Middle Aged ; Recurrence

OBJECTIVE: To observe the therapeutic effect between acupuncture combined with medication and simple medication on migraine and cerebral hemodynamics. METHODS: A total of 120 patients with migraine were randomized into an acupuncture plus medication group (60 cases, 3 cases dropped off) and a medication group (60 cases, 6 cases dropped off). In the medication group, flunarizine hydrochloride capsule was given orally before sleep, 10 mg a day. On the basis of the treatment in the medication group, acupuncture was applied at Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5), Fengchi (GB 20) and etc. in the acupuncture plus medication group, 30 min each time, once a day. Treatment for 4 weeks was required in both groups. Before and after treatment, the visual analogue scale (VAS) score, indexes of cerebral hemodynamic [blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA)] and total TCM syndrome score were observed, and the clinical therapeutic effect and the incidence of the adverse events were evaluated in both groups. RESULTS: Compared before treatment, the VAS scores, the blood flow velocity of ACA, MCA, PCA, VA, BA and the total TCM syndrome scores were decreased in both groups ( CONCLUSION Acupuncture combined with flunarizine hydrochloride capsule can effectively relieve the pain in patients with migraine, reduce the cerebral blood flow velocity, the efficacy is superior to simple flunarizine hydrochloride capsule.
Acupuncture Points ; Acupuncture Therapy ; Hemodynamics ; Humans ; Migraine Disorders/therapy* ; Pain ; Treatment Outcome

OBJECTIVETo analyze the therapeutic efficacy of haploidentical-hematopoietic stem cell transplantation (hi-HSCT) for patients with juvenile myelomonocytic leukemia (JMML).

METHODSThe engraftment of hematopoietic stem cells, incidence of graft versus host disease (GVHD), infection, relapse, and survival of 6 JMML patients received hi-HSCT were retrospectively analyzed.

RESULTSSix (6 males) JMML patients received hi-HSCT from haplo-HLA-matched related donors. The results showed that the hematopoictic stem cells in all 6 patients were grafted successfully. Two cases of JMML died of pulmenary infections, other 4 cases survive without disease. Acute GVHD occurred in 3 patients and chronic GVHD occurred in 1 patients. The overall survival, disease free survival and relapse rates were 66.7%, 66.7%, 0%, respectively.

CONCLUSIONThe hi-HSCT is an effective method for treatment of patients with JMML, but there also is a serial problems to be resolved.

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.
Arthritis, Rheumatoid/drug therapy* ; B-Lymphocytes ; Capsules ; Drugs, Chinese Herbal ; Humans ; Phosphatidylinositol 3-Kinases ; Vascular Endothelial Growth Factor A

Aged ; Cognitive Dysfunction/epidemiology* ; Cross-Sectional Studies ; Geriatric Assessment ; Humans ; Independent Living ; Sarcopenia/epidemiology*