Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

Epithelial splicing regulatory protein 1(ESRP1)is an epithelial cell-specific splicing factor that in-volved in selective splicing and translation of multiple genes.ESRP1 regulates signaling pathways that affect cell proliferation and tumor growth via mediating target genes and regulating cyclic RNA cyclization and biogenesis in a variety of cancers,including head and neck squamous cell carcinoma,carcinoma of colon,and prostate cancer.Through integrating and analyzing the link between ESRP1 and related cancers,provide new ideas for the treatment of tumor cells in which ESRP1 as a key factor.

Objective:To explore the clinical characteristics of pregnancy complicated by primary Sj?gren's syndrome (pSS) and the related factors of adverse outcomes in pregnant women with pSS.Methods:A retrospective analysis was conducted on the clinical data of 32 pregnancies complicated by pSS treated in the Department of Obstetrics at the Third Affiliated Hospital of Guangzhou Medical University from February 2017 to August 2022. The patients were divided into two groups according to whether they had perinatal adverse outcomes: an adverse outcome group ( n=20) and a favorable outcome group ( n=12). The clinical characteristics of the two groups were compared with two independant sample t-test, Mann-Whitney U test, and Fisher's exact test, and multivariate logistic regression analysis was used to analyze the related factors of adverse outcomes in pregnant women with pSS. Results:(1) The average maternal age of the 32 pSS pregnancies was (32.9±4.6) years, the pre-pregnancy body mass index was (21.1±3.8) kg/m 2, and the median gestational age at delivery was 37.8 (35.4-38.5) weeks. There were 18 women (56.3%, 18/32) were diagnosed before pregnancy and 14 women (43.7%, 14/32) during pregnancy. Out of the 32 pregnancies, 25 (79.1%, 25/32) received therapy with glucocorticoids and/or hydroxychloroquine during pregnancy, whereas seven (21.9%, 7/32) had no medication during pregnancy. (2) The main adverse maternal outcomes included oligohydramnios (25%, 8/32), hypertensive disorder of pregnancy (18.8%, 6/32), preterm birth (18.8%, 6/32), fetal growth restriction (15.6%, 5/32), miscarriage (12.5%, 4/32), gestational diabetes mellitus (9.4%, 3/32), and postpartum hemorrhage (3.1%, 1/32). (3) Adverse neonatal outcomes included low birth weight infants in seven cases (25.0%, 7/28), neonatal asphyxia in seven cases (25.0%, 7/28), and two cases of congenital heart block (7.1%, 2/28). (4) The rate of diagnosis before pregnancy in the favorable outcome group was higher than the adverse outcome group [10/12 vs. 40.0%(8/20), Fisher's exact test, P=0.028]. There were no significant differences between the two groups concerning maternal age, pre-pregnancy BMI, weight gain during pregnancy, parity, rates of positivity for autoantibodies (antinuclear antibody, Sj?gren-specific antibody A, Sj?gren-specific antibody B, anti-Ro-52), and proportion of drug treatment (glucocorticoids, hydroxychloroquine) (all P>0.05). (5) Multivariate logistic regression analysis showed that diagnosis before pregnancy ( OR=0.02, 95% CI: 0.00-0.62, P=0.024) and positive Sj?gren-specific antibody B ( OR=0.01,95% CI: 0.00-0.75, P=0.038) were the protective factors. Conclusions:The clinical manifestations of pSS among pregnant women are varied and atypical,often with insidious onset. For pregnant women with pSS, being diagnosed before pregnancy, positive Sj?gren-specific antibody B may reduce adverse outcomes. It is important to address pre-pregnancy examination, early diagnosis and timely intervention to reduce the occurrence of adverse outcomes in pregnant women with pSS.

Objective To evaluate the effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022, so as to provide insights into formulation of future control interventions. Methods Data pertaining to comprehensive echinococcosis control measures with emphasis on management of infectious source and echinococcosis surveillance in Sichuan Province from 2010 to 2022 were collected. The effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source was evaluated with prevalence of human echinococcosis, detection of newly diagnosed echinococcosis patients, prevalence of Echinococcus infection in domestic dogs, prevalence of cystic echinococcosis in livestock, prevalence of alveolar echinococcosis in small mammals and awareness of echinococcosis control knowledge, and Spearman’s rank correlation analysis. Results The prevalence of human echinococcosis reduced from 1.08% in 2010 to 0.40% in 2022 in Sichuan Province (χ² = 1 482.97, P < 0.05), with a reduction from 0.30% to 0.02% in the detection of newly diagnosed echinococcosis cases (χ² = 2 776.41, P < 0.05), a reduction from 15.87% to 0.46% in the prevalence of Echinococcus infection in domestic dogs (χ² = 20 823.96, P < 0.05), a reduction from 8.05% to 1.07% in the prevalence of cystic echinococcosis in livestock (χ² = 1 296.02, P < 0.05), and the awareness of echinococcosis control knowledge increased from 50.65% to 95.24% (χ² = 34 938.63, P < 0.05); in addition, there was a year-specific prevalence rate of alveolar echinococcosis in small mammals (χ² = 164.07, P < 0.05). Spearman’s rank correlation analysis revealed that the detection of newly diagnosed echinococcosis cases correlated positively with the prevalence of Echinococcus infections in domestic dogs (r_s = 0.823, P < 0.05) and the prevalence of cystic echinococcosis in livestock (r_s = 0.795, P < 0.05), and correlated negatively with the awareness of echinococcosis control knowledge (r_s = − 0.918, P < 0.05), and the prevalence of Echinococcus infection in domestic dogs correlated positively with the prevalence of cystic echinococcosis in livestock (r_s = 0.753, P < 0.05) and negatively with the awareness of echinococcosis control knowledge (r_s = −0.747, P < 0.05); however, there was no correlation between the prevalence of Echinococcus infections in domestic dogs and the prevalence of alveolar echinococcosis in small mammals (r_s = −0.750, P > 0.05). Conclusions The comprehensive echinococcosis control measures with emphasis on management of infectious source had achieved remarkable effectiveness in Sichuan Province; however, the transmission chain of echinococcosis has not been interrupted. Reinforced comprehensive echinococcosis control measures with emphasis on management of infectious source and sustained tracking evaluation of the effectiveness are recommended in Sichuan Province.

Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult ; Antigens, CD19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Chimeric Antigen ; Recurrence

Objective:To explore the effect of demographic sociological data on the critical thinking of clinical research nurses, in order to provide reference for improving the level of clinical research.Methods:Using the convenient sampling method, a total of 110 clinical research nurses responsible for clinical research related work in three ClassⅢ Grade A hospitals in Zhengzhou City of Henan Province from January to June 2021 were selected as the research objects. Demographic Sociological Data Questionnaire and Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) were used to conduct surveys among nurses. Multiple linear regression was used to analyze the effect of demographic sociological data on critical thinking of clinical research nurses. A total of 110 questionnaires were distributed, and 106 valid questionnaires were recovered. The effective recovery rate of the questionnaires was 96.36% (106/110) .Results:The total score of CTDI-CV of 106 nurses was (296.25±24.12) . The results of multiple linear regression analysis showed that age, education, professional title and working years were the influencing factors of the level of critical thinking of clinical research nurses ( P<0.05) . Conclusions:The critical thinking ability of clinical research nurses is affected by age, professional title, educational background and working years. It is suggested to take effective measures to improve the critical thinking ability of nurses according to the actual situation, and then improve the clinical research level of nurses.

Primary liver cancer is one of the common malignant tumors and its mortality ranks third in the world. Because there are no obvious symptoms in the early stage of liver cancer, most patients are diagnosed as advanced stage, without the opportunity of surgical resection. The authors report a case of hepatocellular carcinoma with portal vein tumor thrombus, which reduced significantly after hepatic artery infusion chemotherapy combined with bevacizumab and atezolizumab, showing the safety and efficacy.

Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74×10⁹ (0.34×10⁹, 0.94×10⁹)/L vs. 0.99×10⁹ (0.71×10⁹, 1.29×10⁹)/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20)μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m² vs. 22.0 (20.0, 24.0) kg/m², P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25 kg/m², which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all P>0.05). Conclusion COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.

Objective:To explore the clinical value of extra-long subcutaneous tunnel ventricular drainage in patients with hydrocephalus.Methods:From March 2016 to March 2020, 33 patients who were not suitable for ventriculoperitoneal shunt, who would have expected time of external ventricular drainage longer than 7 d, who had external ventricular drainage reaching for 7 d and still could not expect for drainage tube drawing for the next 7 d, or who had hydrocephalus after external ventricular drainage were chosen in our study. These patients accepted extra-long subcutaneous tunnel ventricular drainage. The curative effects in the patients were analyzed retrospectively.Results:The drainage tube was kept for a maximum of 24 months and the shortest time was 13 d, with average of 69.3 d; 32 patients (97%) had drainage time longer than 14 d. There was no secondary infection after operation.Conclusion:Extra-long subcutaneous tunnel extraventricular drainage tube has a long duration of catheter placement, could avoid multiple drainage and secondary intracranial infection, so it is a safe and effective new technology for hydrocephalus.