Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ-glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Young Adult ; Adult ; Stomach Neoplasms/surgery* ; Peritoneal Neoplasms/secondary* ; Hyperthermic Intraperitoneal Chemotherapy ; Percutaneous Coronary Intervention ; Hyperthermia, Induced/methods* ; Combined Modality Therapy ; Laparoscopy/methods* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Perfusion ; Cytoreduction Surgical Procedures ; Survival Rate

Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain. Subcortical regions such as the amygdala are involved in sensory processing including vision and audition, yet their roles in multisensory integration remain unclear. In this study, we systematically investigated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combinations of audiovisual stimuli. From a sample of 332 neurons, we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over unimodal modulation, which could be classified into four types with differentiated regional origins. Using the hierarchical clustering method, neurons were further clustered into five groups and associated with different integrating functions and sub-regions. Finally, regions distinguishing congruent and incongruent bimodal sensory inputs were identified. Overall, visual processing dominates audiovisual integration in the amygdala and adjacent regions. Our findings shed new light on the neural mechanisms of multisensory integration in the primate brain.
Animals ; Macaca ; Acoustic Stimulation ; Auditory Perception/physiology* ; Visual Perception/physiology* ; Amygdala/physiology* ; Photic Stimulation

Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/μl vs 852 cells/μl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.
Animals ; Rabbits ; Humans ; Antilymphocyte Serum/therapeutic use* ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Graft vs Host Disease/drug therapy* ; Transplantation Conditioning

OBJECTIVE: To analyze and compare the efficacy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of thrombocytopenia after chemotherapy in acute leukemia patients. METHODS: 180 patients with acute leukemia complicated with thrombocytopenia after chemotherapy in the First Affiliated Hospital of Anhui Medical University were analyzed retrospectively. Among them, 50 patients who treated with rhTPO and did not receive platelet transfusion were set as group A, 50 patients treated with rhTPO and receive platelet transfusion were set as group B, Forty patients treated with rhIL-11 without platelet transfusion were set as group C, Forty patients who treated with rhIL-11 and received platelet transfusion were set as group D. The duration of PLT below 20×10⁹/L, the days it takes for PLT to recover to more than 100×10⁹/L, and the incidence of different bleeding degrees were compared among several groups. RESULTS: The duration of PLT<20×10⁹/L in group A(3.72±1.14 d) was significantly shorter than that in group C(4.93±1.33 d) (P<0.001), and there was no significant difference from group B (P>0.05). The duration of PLT<20×10⁹/L in group B(3.06±0.91 d) was significantly shorter than that in group D(4.65±0.98 d) (P<0.001), while the difference in duration of days between group C and D was not statistically significant (P>0.05). The times for PLT to recover to 100×10⁹/L in group A(13.46±1.67 d) were significantly shorter than that in group C(16.85±2.13 d) (P<0.05), but there was no significant difference from group B (P>0.05). The time required for PLT to recover to 100×10⁹/L in group B(13.36±1.49 d) were significantly shorter than that in group D(16.18±1.78 d) (P<0.05), while the difference in the days required for group C and group D was not statistically significant (P>0.05). The incidence of high bleeding risk in group B was significantly lower than that in group A (22% vs 44%, P<0.05), the incidence of high bleeding risk in group D was significantly lower than that in group C (32% vs 65%, P<0.05), and the incidence of high bleeding risk in group A was significantly lower than that in group C (44% vs 65%, P<0.05). The incidence of high bleeding risk in group B(22%) was lower than that in group D(32.5%), and the difference was not statistically significant (P>0.05). CONCLUSION In the treatment of acute leukemia patients with thrombocytopenia after chemotherapy, compared with rhIL-11, rhTPO can significantly shorten the duration for patients in a status with extremely low levels of PLT and the recovery time of PLT to normal range. In addition, PLT transfusion cannot speed up the time for patients to raise platelets to a safe range, nor can it shorten the duration of low PLT levels, but it can reduce the incidence of high bleeding risk events.
Humans ; Interleukin-11 ; Leukemia, Myeloid, Acute/drug therapy* ; Platelet Count ; Recombinant Proteins/therapeutic use* ; Retrospective Studies ; Thrombocytopenia ; Thrombopoietin/therapeutic use*

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ² test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ² test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ²=6.971, P=0.008) and nCRT group (6.9% (2/29), χ²=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ²=10.881, P=0.001; χ²=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ²=6.740, P=0.009) and nCRT group (31.0% (9/29), χ²=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ²=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ²=4.976, P=0.083) and progression-free survival (χ²=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.
Adenocarcinoma/pathology* ; Adult ; Aged ; Cohort Studies ; Esophagogastric Junction/pathology* ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Propensity Score

OBJECTIVE: To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD). METHODS: From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc. RESULTS: The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children ( CONCLUSIONS The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.
Autism Spectrum Disorder ; Child ; China ; Copper/analysis* ; Humans ; Trace Elements/analysis* ; Zinc