Objective To investigate the mechanism of Chonghe soft extract on ulcer wound healing in diabetic rats through protein kinase B(Akt)/mammalian Sirolimus target protein(mTOR)-mediated nucleotides binding oligomeric acid domain-like receptor protein 3(NLRP3)inflammasome inactivation.Methods Thirty six SD rats with diabetic ulcer,which were established by feeding with high glucose and high fat diet and injecting intraperitoneally with streptozocin(STZ)combined with skin defect,were randomly divided into model group,Chonghe soft extract group and growth factor group,with twelve rats in each group.Another twelve SD rats were injected an equal dose of citric acid-sodium citrate buffer solution and used as blank group.The blank group and the model group were not received drug intervention,but the Chonghe soft extract group and the growth factor group were externally applied Chonghe soft extract and growth factor gel,respectively.The wound healing of each group was observed and recorded.After 7 days and 14 days of treatment,the histopathology of wound were observed by HE staining and the number of fibroblasts were counted.The levels of IL-1β,IL-18 and TNF-α in serum were detected by ELISA.The expression of autophagy-related protein Beclin-1 and LC3Ⅱ in granulation tissue was detected by immunohistochemistry.The expression of NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),Caspase1,Pro-Caspase1 and Akt/mTOR autophagy pathway-related proteins Akt,p-Akt,mTOR and p-mTOR were detected by Western Blot.Results Compared with the blank control group,the pathological wound repair of the model group was delayed on the 7th day and 14th day,the number of fibroblasts per unit area was decreased(P<0.01).The levels of IL-1β,IL-18 and TNF-α were increased(P<0.01).The expression levels of ASC,Pro-Caspase1,Caspase1,and NLRP3 were increased in the wound tissues(P<0.01),while the expression levels of Beclin-1,LC3-Ⅱ,mTOR,p-mTOR,Akt and p-Akt were decreased in the wound tissues(P<0.01).Compared with the model group,the pathological injury in Chonghe soft extract group and growth factor group was significantly improved on the 7th day and 14th day.The number of fibroblasts per unit area was significantly increased(P<0.01).The levels of IL-1β,IL-18 and TNF-α were significantly decreased(P<0.01).The expression levels of ASC,Pro-Caspase1,Caspase1,and NLRP3 in the wound tissues were decreased(P<0.01),while the expression levels of Beclin-1,LC3-Ⅱ,mTOR,p-mTOR,Akt and p-Akt were increased(P<0.01,P<0.05).Conclusion Chonghe soft extract can reduce inflammatory reaction,promote the generation of fibro,regulate the Akt/mTOR-mediated NLRP3 inflammasome inactivation,improve the level of autophagy in wound,and promote ulcer wound healing in diabetic rats.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective:To investigate the efficacy and safety of venetoclax combined with the decitabine, cytarabine, and homoharringtonine (HHT) regimen and donor lymphocyte infusion (DLI) for the preventive and salvage therapy of pediatric acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (HSCT) .Methods:A total of 29 relapsed pediatric/minimal residual disease-positive AML after HSCT were recruited at the Peking University Institute of Hematology from January 1, 2021, to June 1, 2023. They were treated with the above combination regimen and administered with DLI after 24-48 hours at the end of chemotherapy, and the treatment response and adverse reactions were regularly assessed.Results:The overall response rate (ORR) was 75.8%, CR rate was 88.9% (8/9) in the hematologic relapse group, and MRD negativity rate was 61.1% (11/18) in the MRD-positive group. The incidence of agranulocytosis, anemia, and thrombocytopenia with a classification above grade 3 were 100%, 82.7%, and 100%, respectively. The median time of the granulocyte deficiency period was 15 days. Acute graft-versus-host diseases (aGVHD) with a classification of grades Ⅲ-Ⅳ occurred in 11.1% of the patients after DLI, while moderate or severe cGVHD occurred in 7.4% of the patients. The single risk factor for ORR was MNC counts of less than 10×10 8/kg, and the relapse occurred within 100 days. At a median follow-up of 406 days, the 1-year OS was 65%, and the 1-year OS was 57% in the group with no reaction ( P=0.164) compared with 71% in the group who had an overall reaction. Conclusion:The combined regimen based on the DAC, VEN, and modified HA regimen showed a high response rate in the salvage therapy for pediatric AML after the relapse of HSCT. However, bridging to transplantation should be performed immediately after remission to result in a long survival rate.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the risk factors of invasive fungal disease after haploid hematopoietic stem cell transplantation in children with acute leukemia.Methods:Four hundred and two children (median age 10 years) with acute leukemia, undergoing haplo-HSCT at this institutute from January 2016 to December 2020,were analyzed retrospectively according to the diagnosis criteria of IFD. The basic information and preoperative indicators of the children were collected, including gender, age, primary disease, remission status of primary disease, and previous IFD history. Postoperative indicators were collected, including long-term granulocyte deficiency time, high-dose glucocorticoids, using CD25 monoclonal antibody, acute and chronic graft-versus-host disease. Count data are expressed as example (%), and comparisons between groups are made using the continuously multifactorial corrected Chi-square test or Fisher exact probability method. Logistic regression model was used to analyze the risk factors of IFD after haplo-HSCT in children.Results:Among 402 cases, 250 were male and 152 were female. The median age at transplantation was 10 years, and the age range was 9 months to 17 years 7 months. Before transplantation, 390 cases achieved complete remission of the primary disease, 9 cases had partial remission, and 3 cases had no remission. The implantation time of neutrophils ranged from +10 to 24 days, with a median time of 12 days. IFD occurred in 17 cases (4.2%), of which 3 cases (0.7%) were proven IFD and 14 cases (3.5%) were probable IFD. IFD occurred from 13 to 275 days after transplantation, with a median time of 30 days. The lungs were the most common site of infection (88.2%,15/17). The multivariate Logistic regression analysis showed that age >10 years old ( P=0.046, odds ratio =3.05, 95% confidence interval: 1.02~9.13), the use of high-dose corticosteroids ( P=0.005, odds ratio =7.72, 95% confidence interval: 1.85~32.20) were risk factors for IFD after haplo-HSCT in children. Conclusions:IFD is an important complication after haplo-HSCT in children with acute leukemia. Age >10 years and the use of high-dose corticosteroid are risk factors for IFD after haplo-HSCT in children with acute leukemia.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

ObjectiveTo investigate the iodine nutritional status of residents in Shanxi province,and to provide a scientific basis for adjustment of control strategies and measures to iodine deficiency disorders (IDD).MethodsIn the 11 cities and 119 counties(cities,districts),except high water iodine townships,9 townships were selected in each county according to their sub-area positions of east,west,south,north and center,4 villages were sampled in each chosen township,and 8 households were selected in each chosen village in every chosen county (cities,districts ) with 9 or more townships.In every chosen county (cities,districts) with 6 to 9 townships,1 township was selected respectively in east,west,south,north and center sub-areas of the township,4 villages were sampled in each chosen township,and 15 households were selected in each chosen village.In the county (cities,districts) with 5 or less townships,all township were selected,4 villages were sampled in each chosen township,and 15 households were selected in each chosen village.Edible salt samples from these households were collected; iodized salt was determined by direct titration.In the 119 counties(cities,districts),1 township was selected,respectively,in east,west,south,north and center sub-areas in each county,and 20 children aged 8 - 10 in each of the selected townships were selected to collect urine samples and urinary iodine was determined by As-Ce catalytic spectrophotometry.Evaluation criteria:median urinary iodine ＜ 100 μg/L was iodine deficiency,100 - 199 μg/L as appropriate,200 - 299 μg/L as more than appropriate,and ≥ 300 μg/L as iodine excess.ResultsMedian iodine of the 34 808 household salt samples was 31.55 mg/kg.The coverage rate of qualified iodized salt was 99.18％(34 521/34 808) and the consumption rate of qualified iodized salt was 97.12％(33 805/ 34 808).In the 11 cities,119 counties(cities,districts),the median of urinary iodine of 11 967 children aged 8 -10 was 244.0 μg/L,of which ＜ 50 μg/L acoounted for 2.6％(312/11 967),50 - 99 μg/L accounted for 6.9％(823/11 967),100- 199 μg/L accounted for 26.3％(3145/11 967),200 - 299 μg/L accounted for 28.7％(3440/11 967),and 300 μg/L or higher accounted for 35.5％(4247/11 967).The medians of urinary iodine in the 9 municipal cities were 200 - 300 μg/L,and other 2 cities were 300 - 400 μg/L At the county level,the medians urinary iodine of children of the 119 counties(cities,districts) were 100 - 199 μg/L that accounted for 15.1％(18/119),200 - 299 μg/L accounted for 63.9％(76/119),and 300 μg/L or higher accounted for 21％(25/119).Conclusions The iodine nutrition level of residents in Shanxi province is more than appropriate.The salt iodine concentration in Shanxi province needs to be reduced,but the space is not wide.

Objective To explore the long-term effect of endemic arsenism on oxidative stress and immune function, and to provide scientific basis for prevention and treatment of the disease in the areas. Methods In 2009, Using cluster sampling and typical investigation, the cross-sectional study was completed. The patient groups and the internal control group were selected in the arsenism areas after 5 years quality improvement of drinking water(Silizhuang village, Daying village and Gucheng village in Shanyin county, Gucheng city, Shanxi province) and they were divided into mild, moderate, severe case and internal control groups, respectively. The external control group was selected in a non-arsenism area(Yangzhuang village in Heshengbu city). The Oxidative stress indicators were determined and analyzed [serum superoxide dismutase (SOD) activity was determined with xanthine oxidase method, glutathione peroxidase(GSH-Px) activity was determined with 2-thio-2-nitrobenzoic acid method, and mmuuity malondisldohyde(MDA) levels was determined with thiobarbituric acid method]. The immune function was determined and analyzed [immunoglobulin G (IgG) was determined with radioimmunoassay method, and serum lysozyme was determined with turbidimetric method]. Results A total of 252 people were surveyed, in which the external control group, the internal control group, mild, moderate and severe patient groups were 56, 57, 49,44 and 46, respectively. Serum SOD activities were (72.19 ± 11.75), (66.96 ± 12.02), (49.79±11.07), (48.54 ±10.56) and (47.68 ± 10.68)kU/L, respectively. The difference of serum SOD activities between the groups was statistically significant(F = 52.42, P ＜ 0.01 ). Serum SOD activities in the external control group were significantly higher than other groups (all P ＜ 0.05). The value in the internal control group was significantly higher than the 3patient groups (all P ＜ 0.05). There were no significant differences between the case groups (P ＞ 0.05). Serum GSH-Px activities of the five groups were (197.41 ± 38.54), (195.02 ± 31.93), (187.26 ± 28.22), (187.24 ± 25.40),(186.88 ± 21.84)U/mg, respectively, and the difference between the groups was not significant(H = 4.21, P ＞0.05). Serum MDA levels of the five groups were (4.51 ± 2.14), (5.88 ± 2.00), (6.44 ± 2.83), (5.89 ± 2.57),(5.88 ± 2.40)μ mol/L, respectively, and the difference between the groups was statistically significant(F = 3.36,P ＜ 0.05). The external control group was significantly lower than other groups(all P ＜ 0.05). No significant difference was observed between other groups(all P ＞ 0.05). Serum IgG levels were(11.16 ± 2.08), (8.15 ± 1.44), (8.77 ±2.54), (9.19 ± 1.97), (8.44 ± 2.52)g/L, respectively, and the difference between the groups was statistically significant(H = 52.92, P ＜ 0.01 ). The external control group was significantly higher than other groups(all P ＜0.05). No significant difference was observed between other groups(all P ＞ 0.05). Serum lysozyme levels were (13.57 ± 5.16), (10.05 ± 3.96), (8.78 ± 3.35), (8.72 ± 3.76), (9.38 ± 4.26)mg/L, respectively, and the difference between the groups was statistically significant (H = 35.00, P ＜ 0.01 ). The external control group was significantly higher than other groups(all P ＜ 0.05). No significant difference was observed between other groups(all P ＞ 0.05). Conclusions The effect of arsenic on the body's oxidative stress response and immune function persists after 5 years of drinking low arsenic water. In addition to intensify arsenic removal from drinking water, it should also strengthen the monitoring of population's health in the diseased areas.

OBJECTIVE: To improve the diagnostic and therapeutic efficiency for secondary laryngeal tuberculosis through an analysis on the clinical features of patients with this disease. METHOD: A retrospective study was made among 49 cases with laryngeal tuberculosis treated in Tibetan General Hospital of Chinese PLA, and the clinical data were carefully analyzed to summarize the clinical experience of this disease. RESULT: Of 49 patients, 24 cases had 1 year history, 11 cases had 1 to 3 years, 9 cases had 3 to 5 years, 5 cases had 5 years or more. Thirty-eight patients had the history of tuberculosis and 11 had none. Thirty-four patients had taken anti-tuberculosis drugs but none had standard therapy as demanded. All cases had mild general symptoms (mild fever, night sweats, weight loss, et al) and atypical local symptoms (hoarseness, sore throat). Therefore, 42 cases were misdiagnosed as non-specific chronic laryngitis, of which 15 cases got worse after oral administration or inhaling of steroid hormones. Seven persons were misdiagnosed as laryngeal cancer. All patients were confirmed pulmonary tuberculosis by X ray exam or CT scanning. Twelve cases had strong positive PPD tests and 2 cases were detected positive by sputum smear. All patients was treated by standard systematic and local chemical therapy against tuberculosis (inhaling of antituberculosis drugs for 1 to 2 months). All were cured but one died in a road accident, and none had recurrence after 1- to 9- year follow-up. CONCLUSION All of those the patients with long period hoarseness and sore throat should take chest CT scan or X-ray exam for the highest incidence of pulmonary tuberculosis at high altitudes. CT scanning is the prefer for its high resolution. Pathological biopsy and diagnostic therapy should be taken to make accurate diagnosis. Usually steroid hormones should not be recommended.
Adolescent ; Adult ; Aged ; Altitude ; Child ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tibet ; Tuberculosis, Laryngeal ; diagnosis ; drug therapy ; Young Adult