OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans ; Adrenocorticotropic Hormone ; Hot Temperature ; Medicine, Chinese Traditional ; Adenosine Triphosphate

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.
Humans ; Fecal Microbiota Transplantation/methods* ; Treatment Outcome ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Steroids

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective To study the clinical features and prognostic factors of patients with acute paraquat poisoning.Methods The clinical data of 108 patients with acute paraquat poisoning in Affiliated Hospital of Southwest Medical University from June 2013 to June 2015 were collected and followed up for half a year.The clinical features and prognostic factors were analyzed.Results Of 108 patients,about 90.00％ cases were from the rural areas,the married population accounted for 81.48％.Among them,53 people were living,55 cases were dead,and the death rate was 51.00％.The average amount of poison,average hospitalization time,poison to gastric lavage time interval in the survival group were (22.08 ±5.32) mL,(16.5 ± 3.72) d,(2.00 ±0.49) h,respectively,which in the death group were (88.12 ± 14.96) mL,(5.50 ± 1.20) d,(8.56 ± 1.65) h,respectively.The average amount of poison in the death group was far greater than that of the survival group,about 3.6 times,and the average hospitalization time was significantly reduced,only 1/3 of the survival group.The gastric lavage time interval was also lengthened 1.7 times than that of the survival group,the differences were statistically significant (all P ＜ 0.05).The proportions of fever,increased serum creatinine,liver function damage and pulmonary fibrosis in the death group were significantly higher than those in the survival group,the differences were statistically significant (x2 =12.20,8.35,8.84,50.68,all P ＜ 0.05).Conclusion Mortality rates are still high in patients with acute paraquat poisoning.The amount of poison is still the key factor of death in patients.Early gastric lavage and blood purification,as soon as possible to clear the poison,as far as possible to reduce the absorption of the toxic chemical and aggressive treatment can significantly improve the prognosis of patients.Early fever,liver and kidney function damage and pulmonary fibrosis may predict the poor prognosis of patients.

Objective To survey avian influenza A viruses (AlVs) in the environment and explore the reasons for the surge in human H7N9 cases.Methods A total of 1,045 samples were collected from routine surveillance on poultry-related environments and 307 samples from human H7N9 cases-exposed environments in Henan from 2016 to 2017.The nucleic acids of influenza A (Flu A),H5,H7,and H9 subtypes were detected by real-time polymerase chain reaction.Results A total of 27 H7N9 cases were confirmed in Henan from 2016 to 2017,24 had a history of live poultry exposure,and 15 had H7N9 virus detected in the related live poultry markets (LPMs).About 96％ (264/275) Flu A positive-environmental samples were from LPMs.H9 was the main AIV subtype (10.05％) from routine surveillance sites with only 1 H7-positive sample,whereas 21.17％ samples were H7-positive in H7N9 cases-exposed environments.Samples from H7N9 cases-exposed LPMs (47.56％)had much higher AIVs positive rates than those from routine surveillance sites (12.34％).The H7+H9 combination of mixed infection was 78.18％ (43/55) of H7-positive samples and 41.34％ (43/104) of H9-positive samples.Conclusion The contamination status of AIVs in poultry-related environments is closely associated with the incidence of human infection caused by AlVs.Therefore,systematic surveillance of AlVs in LPMs in China is essential for the detection of novel reassortant viruses and their potential for interspecies transmission.

AIM: To investigate hemodynamic alterations of retrobulbar vessels in proliferative diabetic retinopathy ( PDR) patients with anterior segment neovascularization, before and 3mo after vitrectomy combined with panretinal photocoagulation and to explore the clinical significance.
●METHODS: Color Doppler flow imaging ( CDFl ) was used for measurement of blood flow velocities and resistive indexes ( Rl ) of the ophthalmic artery ( OA ) , short posterior ciliary arteries ( sPCA ) and central retinal artery ( CRA ) in 21 eyes of 21 PDR patients with anterior segment neovascularization. CDFl parameters were obtained before and 3mo after vitrectomy combined with panretinal photocoagulation ( PRP) .
● RESULTS: Peak systolic velocity ( PSV ) and end diastolic velocity ( EVD ) of CRA were significantly increased after surgeries, Rl were decreased significantly (P<0. 05). Parameters of sPCA and OA have no change after surgeries (P>0. 05).
●CONCLUSION: Vitrectomy combined with panretinal photocoagulation might increase the velocity of CRA, decrease Rl and improve ocular blood supply postoperatively. lt may delay or prevent the process of neovascular glaucoma.

OBJECTIVETo observe the effect of Bushen Wenyang Huayu Recipe (BWHR) on hypoxia inducible factor-1α (HIF-1α), proline hydroxylase2 (PHD2), von Hippel Lindau disease (VHL) suppressor gene expressions in endometriosis (EM) rats with Shen yang deficiency blood stasis syndrome (SYDBSS), and to explore the pathogenesis of EM and the mechanism of BWHR for treating EM.

METHODSTotally 50 SD rats were randomly divided into five groups, i.e., the blank control group, the sham-operation group, the model group, the Chinese medicine (CM) group, and the Western medicine (WM) group, 10 in each group. Rats in the blank control group and the sham-operation group were fed routinely. Rats in the rest 3 groups received 30-day "extended refrigerator freezing and ice water immersion" and combined with " autotransplantation" to establish EM rat model with SYDBSS. One Milliliter BWHR at 3.33 g/mL was administered to rats in the CM group by gastrogavage. Gestrinone at the daily dose of 0. 5 mg/kg was administered to rats in the WM group by gastrogavage. Equal volume of normal saline was administered to rats in the model group, the blank control group, and the sham-operation group. The size and morphology of ectopic foci in rats were observed after 4 weeks of medication. Expressions of serum CA125, plasma cyclic adenosine monophosphate (cAMP), and plasma cyclic guanosine monophosphate (cGMP) were detected by radioimmunoassay. Morphological changes of eutopic endometrium and ectopic tissue were observed under the optical microscope by HE staining. Protein expressions and contents of HIF-lα, PHD2, and VHL were detected by immunohistochemical SABC method and Western blot. mRNA expressions of HIF-1α, PHD2, and VHL were detected by RT-PCR.

RESULTSThe ectopic foci grew significantly in the model group. Their volumes were obviously contracted after treated by CM and WM. Compared with the blank control group and the sham-operation group, serum CA125 and plasma cGMP obviously increased, cAMP obviously decreased (P < 0.05); expressions and contents of HIF-1α mRNA and protein all decreased (P < 0.05); mRNA and protein expressions and contents of PHD2 and VHL all decreased in the model group (P < 0.05). Compared with model group, levels of CA125 and cGMP obviously decreased; cAMP levels obviously increased, expressions and contents of HIF-1α mRNA and protein all increased, mRNA and protein expressions and contents of PHD2 and VHL all increased in the WM group and the CM group (P < 0.05). Compared with the CM group, PHD2 protein contents were higher in the WM group (P < 0.05). HIF-1α was negatively correlated with PHD2 (r = -0.799, P = 0.00). HIF-1α was negatively correlated with VHL (r = -0. 625, P = 0.003).

CONCLUSIONSBWHR could effectively treat EM. Its mechanism might be associated with reducing contents of HIF-1α, serum CA125, and plasma cGMP, and up-regulating expressions of PHD2, VHL, and cAMP.

Animals ; Cyclic AMP ; Drugs, Chinese Herbal ; therapeutic use ; Endometriosis ; drug therapy ; metabolism ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Proline ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Up-Regulation ; Yang Deficiency ; drug therapy ; metabolism

OBJECTIVETo observe the effect of Tongsaimai (TSM) tablets in treating foot trauma of diabetic foot (DF) model rats, and discuss its potential mechanism.

METHODMale SD rats were selected to duplicate the diabetic foot ulcer model and randomly divided into the blank control group, the model group, the metformin treatment group, and TSM 12.44, 6.22, 3.11 g x kg(-1) groups (n = 10). The healing of ulcer wounds were observed on day 1, 4, 8, 13 and 18. After 18 days, a histopathologic examination was conducted for ulcer tissues. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by hydroxylamine and TBA methods. The content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined with the radioimmunoassay. The immunohistochemical method was used to observe the expression of vascular endothelial growth factor (VEGF) in ulcer tissues and the number of capillary vessels.

RESULTTSM could alleviate the pathological changes of diabetic foot rats, accelerate the ulcer healing on 4, 8, 13, 18 d, reduce MDA, IL-6, TNF-alpha, VEGF content in rat serum at 18 d (after the rehabilitation period), and enhance the SOD content. Specifically, the TSM 12.44 g x kg(-1) group showed significant differences compared with the model group (P < 0.05, P < 0.01). At 18 d after the treatment (the late rehabilitation period), the VEGF expression of TSM 12.44, 6.22 g x kg(-1) groups and the number of blood capillaries of the TSM 12.44 g x kg(-1) group were significantly lower than that of the model group (P < 0.05, P < 0.01).

CONCLUSIONTSM could promote the foot wound healing of DF model rats, reduce MDA, IL-6 and TNF-alpha levels in serum, increase the SOD content and decrease the VEGF expression and the number of blood capillaries in the late rehabilitation period. Its action mechanism may be related to the inhibition of oxidative stress injury and the inflammatory cell infiltration.

Animals ; Diabetic Foot ; drug therapy ; genetics ; metabolism ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Interleukin-6 ; genetics ; metabolism ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; genetics ; metabolism ; Tablets ; administration & dosage ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Wound Healing ; drug effects

In 2013, the first dengue fever (DF) outbreak in central China was reported in the central of Henan province, northern temperate regions, although they have been sequentially recorded in Southern China. 106 suspected DF cases were reported and 73 patients were confirmed dengue virus type 3 (DEN-3) infections. 62/392 (15.8%) local health persons showed DEN antibodies positive. To this day Henan is the northernmost province in China which has been reported about outbreak of DF and what is important is that it warns us the endemic range of DF has been expanded geographically in China.
Adolescent ; Adult ; Aged ; Antibodies, Viral ; blood ; Child ; Child, Preschool ; China ; epidemiology ; Dengue ; epidemiology ; virology ; Dengue Virus ; isolation & purification ; Disease Outbreaks ; statistics & numerical data ; Female ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Infant ; Male ; Middle Aged ; Serologic Tests ; Young Adult