OBJECTIVE: To investigate the efficacy and safety of diagnostic-driven therapy for invasive fungal disease(IFD) in patients with myeloid hematologic malignancies. METHODS: A retrospective analysis was conducted on the clinical data of 91 patients with myeloid hematologic malignancies who received diagnostic-driven therapy for IFD at the Second Hospital of Anhui Medical University from January 1, 2020 to December 31, 2023. The patients were divided into two groups based on medication: 44 patients in the caspofungin group and 47 patients in the voriconazole group. The clinical efficacy and adverse reactions of the two groups were compared and analyzed. RESULTS: The overall response rates in the caspofungin and voriconazole groups were 67.4% and 60.0%, respectively. Among patients who transitioned to diagnostic-driven therapy following prophylactic or empirical treatment with triazole antifungal agents, the response rate of the caspofungin group was significantly higher than that of the voriconazole group (76.9% vs 35.3%, P <0.05). A total of 9 patients in both groups experienced adverse reactions, and no grade III or higher adverse reactions occurred. The incidence of grade I-II adverse reactions in the caspofungin group was lower than in the voriconazole group (2.3% vs 17.0%, P <0.05). CONCLUSION In patients with myeloid hematologic malignancies, caspofungin and voriconazole demonstrate comparable clinical efficacy in diagnostic-driven therapy for IFD, but caspofungin is associated with a lower incidence of adverse reactions. Caspofungin exhibits significant effectiveness when initiating diagnostic-driven therapy after prophylactic or empirical treatment with broad-spectrum triazole antifungal agents.
Humans ; Retrospective Studies ; Hematologic Neoplasms/complications* ; Antifungal Agents/therapeutic use* ; Voriconazole/therapeutic use* ; Caspofungin/therapeutic use* ; Invasive Fungal Infections/diagnosis* ; Male ; Female ; Mycoses/drug therapy* ; Middle Aged ; Treatment Outcome ; Aged ; Adult

This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.

Objective:To establish an efficient gene editing method of HLA-Ⅰ gene to prepare HLA-Ⅰ universal hematopoietic stem cells.Methods:The easyedit small guide RNA(sgRNA)was designed according to the sequences of β2 microglobulin gene and synthesized by GenScript company. RNP complexes were formed by NLS-Cas9-NLS nuclease and Easyedit sgRNA according to different molar ratios (1∶1～1∶4 ).Control group and four transfection groups were performed respectively.HEK-293 cells and CD34+hematopoietic stem cells were nucleotransfected with RNP complex by Lonza 4D Nucleofector system.The expression of HLA-Ⅰ on the surface of HEK-293 cells was detected by flow cytometry after transfection for 72 hours,the cleavage effect was determined by T7E1 enzyme digestion reaction and the presence of nested peak in the DNA sequence was identified by direct sequencing.Results:The transfection groups had different levels of HLA-Ⅰ negative expression cell populations by flow cytometry after transient transfection of HEK-293 cells and CD34+hematopoietic stem cells with different molar concentrations of RNP complex for 72 hours. There were nested peaks proximal to the sgRNA PAM sequence in the transfection groups by direct DNA sequencing,indicating that sgRNA had obvious editing effect.In the transfection of HEK-293 cells,the highest proportion of HLA-Ⅰ negative expression cells was (87.69±0.83)％ when the molar ratio of NLS-Cas9-NLS nuclease to Easyedit sgRNA was 1∶4.The cutting efficiency of T7E1 was the highest up to (38±2.0)％ when the molar ratio was 1∶3.In the transfection of CD34+hematopoietic stem cells,the proportion of HLA-Ⅰ negative expression cells was (91.56±3. 39)％when the molar ratio was 1∶2,and the cutting efficiency of T7E1 was (64±8.45)％when the molar ratio was 1∶1 .Conclusion:This study provides an efficient gene editing method for classical HLA-Ⅰ molecules,which can effectively silence the expression of class HLA-Ⅰ molecules on the cell surface,and is suitable for stem cell system with difficult transfection.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

Immune thrombocytopenia (ITP) is an immune-mediated acquired hemorrhagic autoimmune disease. At present, the first-line therapeutic drugs for ITP include glucocorticoids and intravenous immunoglobulins. However, about 1/3 of the patients had no response to the first-line treatment, or relapsed after dose reduction or withdrawal of glucocorticoids. In recent years, with the gradual deepening of the understanding on the pathogenesis of ITP, the drugs targeting different pathogenesis continually emerge, including immunomodulators, demethylating agents, spleen tyrosine kinase (SYK) inhibitors and neonatal Fc receptor (FcRn) antagonist. However, most of these drugs are in clinical trials. This review summarized briefly the recent advances in the treatment of glucocorticoids resistance and relapsed ITP, so as to provide reference for the clinical treatments.
Infant, Newborn ; Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Glucocorticoids/therapeutic use* ; Thrombocytopenia ; Immunoglobulins, Intravenous/therapeutic use* ; Immunologic Factors/therapeutic use*

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ²=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ²<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ²<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ²=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ²=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.
Male ; Humans ; Female ; Young Adult ; Adult ; Helicobacter Infections ; Helicobacter pylori ; Bismuth ; Anti-Bacterial Agents/therapeutic use* ; Amoxicillin/adverse effects* ; Drug Therapy, Combination ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Objective: To analyze the safety of an inactivated 2019-nCoV vaccine (Vero cell) in adults aged 60 years and older. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted in May 2020 The eligible residents aged 60 and above were recruited in Renqiu city, Hebei Province. A total of 422 subjects (phase Ⅰ/Ⅱ:72/350) were enrolled. Two doses of the trial vaccine or placebo were randomly administered according to a 0 and 28-day immunization schedule. Subjects were randomly divided into two groups in Phase Ⅰ. Within each group, participants received vaccine or placebo in a ratio of 2∶1. Subjects were randomly divided into four groups in phase Ⅱ to receive low-dose, medium-dose, high-dose vaccine and placebo, respectively, in a ratio of 2∶2∶2∶1. A combination of regular follow-up and active reporting was used to observe adverse reactions within 28 days after vaccination, and compare the incidence rate of adverse reactions in the trial and control groups. Results: 422 subjects were (66.45±4.70) years old, and 48.82% were male (206/422). There were 100, 124, 124 and 74 patients enrolled into the low-dose, medium-dose, high-dose vaccine groups and the placebo group, respectively. One person without the vaccination was removed, and 421 participants who received at least one dose of vaccine were included in the safety analysis. Within 28 days after the first or second dose, a total of 20.67% (87/421) subjects had adverse reactions (both solicitation and non-solicitation). About 76 patients suffered grade 1 adverse reactions [18.05% (76/421)] and 22 patients suffered grade 2 adverse reactions [5.23% (22/421)]. No grade 3 or above adverse reactions occurred. A total of 19.71% (83/421) subjects had solicited adverse reactions. The most common grade 1 adverse reaction was injection site pain, followed by fever and fatigue. The most common grade 2 adverse reactions were fever and fatigue, followed by muscle pain and injection site redness. A total of 2.61% (11/421) subjects had unsolicited adverse reactions. A total of 1.66% (7/421) subjects had serious adverse events after vaccination, and no serious vaccine-related adverse events were reported. Conclusions: The inactivated SARS-CoV-2 vaccine is safe for people aged 60 years and above.
Adult ; Aged ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines ; Fatigue ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Vaccination

Objective To investigate the multiple correspondence of genetic and environmental risk factors with abnormal birth history and provide a scientific basis for improving the birth defects surveillance system and reducing the incidence of birth defects. Methods Data were collected from all the perinatal infants from 28-week-old fetuses to 7-day-old infants born in all the hospitals with obstetrical department in Xi'an from 2003 to 2015. Results A total of 1 236 937 perinatal infants were surveyed,including 10 619 with birth defects.The average incidence rate of birth defects was 0.86% (0.70%-1.15%).Multiple correspondence analysis showed that the women who had had 1 or 2 children with birth defects were associated with the history of spontaneous abortion,family history of birth defects,and history of exposure to toxic and harmful substances.The women who had had 3 or more children with birth defects showed stronger association with family history of birth defects.The birth defects in women with history of spontaneous abortion (257/10 619) was ranked in the order of congenital heart disease,polydactyly,neural tube defects,congenital hydrocephalus,cleft lip with cleft palate,and simple cleft lip.The birth defects in women who had given birth to children with birth defects (135/10 619) followed the order of cleft lip with cleft palate,anencephaly,hydrocephalus,neural tube defects,cleft lip,and talipes equinovarus. Conclusions Abnormal birth history is associated with family history of birth defects and history of exposure to environmental risk factors.Giving birth to three or more children with birth defects is highly correlated with the family history of birth defects.
Child ; Pregnancy ; Female ; Humans ; Cleft Lip/etiology* ; Cleft Palate/complications* ; Reproductive History ; Abortion, Spontaneous ; Neural Tube Defects/epidemiology* ; Risk Factors

Actin-binding proteins (ABPs) are important components of the F-actin cytoskeleton and affect the dynamics of F-actin by promoting the polymerization and depolymerization of actin. Numerous studies have shown that F-actin and actin-binding proteins are involved in all stages of carcinogenesis. Our analysis of esophageal carcinoma proteomic data showed that the actin-binding protein EHD2 (E p s l 5 homology domain-containing protein 2) is expressed at low levels in esophageal squamous cell carcinoma tissues and patients with lower EHD2 expression had poorer prognosis. Previous studies have revealed that EHD2 is involved in the regulation of glucose metabolism, autophagy and tumor cell migration. However, the role and mechanism of EHD2 in esophageal squamous cell carcinoma progression remain unclear. This study aimed to explore the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. Immunofluorescence and cell fractionation analysis showed that EHD2 was not only localized in the cell membrane and cytoplasm, but also in the nucleus. Colony formation, EdU labeling and flow cytometry were used to determine the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. The results showed that overexpression of EHD2 and EHD2-3×NLS (nuclear localization signal) inhibited proliferation, cell cycle G