T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To characterize the distribution and assess the exposure to phthalic acid esters （PAEs） in the indoor dust of Shanghai City. Methods Samples were collected from 33 sampling sites， including homes， hotels， offices and public places， in Shanghai in 2018， 2019， and 2020. The samples were pretreated by 100 sieves， extracted and concentrated， and then analyzed by gas chromatography-mass spectrometry in selected ion mode （SIM）. Results Results on the characteristics of PAEs in indoor dust in different places showed that concentrations of PAEs were in a range of <0.01-2 464 mg·kg^-1.The average concentration of 16 PAEs was 613 mg·kg^-1. Bis（2-ethylhexyl） phthalate （DEHP）， di-iso-butyl phthalate （DiBP）， di-n-butyl phthalate （DBP） and di-n-octyl phthalate （DnOP） were the main components of PAEs in indoor dust， accounting for approximately 99.5% of 16 PAEs. The intake of DEHP， DBP， DEP and BBP was lower than the tolerable daily intake （TDI） and reference doses （RfD） set by EU CSTEE and U.S. EPA. Conclusion Average daily dose （ADD） via indoor dust is estimated， and the order of intake through different pathways is hand-oral intake>skin contact>respiratory inhalation. Exposure risk of PAEs in children is greater than that in adults.

Objective:To explore the impact of adverse drug events (ADE) on readmission in renal transplant recipients and survival of the transplanted kidney.Methods:The hospital information system was searched and medical records of patients who underwent renal transplantation in Beijing Road Medical Area of Xinjiang Military Region General Hospital from January 2008 to December 2018 and were re-admitted at least once (as of December 2020) were collected and analyzed retrospectively. Patient information such as gender, age, weight, ethnicity, kidney transplantation status, postoperative immunosuppressive treatment plan, readmission status, and kidney transplant survival time was extracted and the ADE signals were detected through reviewing the patient re-admission medical history using a self-established global trigger tool. The correlation between ADE and readmission was evaluated by Karch and Lasagna method; patients were included in the ADE-related readmission group (ADE admission group) and the non-ADE-related readmission group (non-ADE admission group) based on the correlation results. The clinical characteristics and the cumulative survival rate of kidney transplants between the 2 groups were compared.Results:A total of 198 patients (1 426 times of readmission) were entered in the analysis, including 154 males and 44 females with an age of 14-62 years, and 118(59.6%) were Han nationality. The immunosuppressive drugs included cyclosporine, tacrolimus, sirolimus, etc. After renal transplantation, 240 times of readmission (16.8%) in 94 patients (47.5%) were associated with ADE. In the ADE readmission group, the number of diagnosed diseases and postoperative readmission times were more and the length of hospital stay was longer than those in the non-ADE readmission group [4 (3,6) vs. 3 (2,5), P=0.001; 6(3, 9) times vs. 4 (2, 8) times, P=0.022; 20(13, 33) days vs. 14 (11, 25) days, P=0.010]. Kaplan-Meier curve showed that the 1-, 3-, 5-, and 10-year cumulative survival rates of kidney transplants were 90.1%, 84.1%, 79.0%, and 57.6% in ADE-related readmission group, which were 99.0%, 94.7%, 90.8%, and 80.4% in non-ADE-related readmission, and the difference was statistically significant ( P=0.001). Conclusions:ADE can increase the readmission times, prolong the length of hospital stay, and reduce the cumulative survival rate of kidney transplants. The monitoring of ADE in renal transplant recipients should be strengthened.

Objective:To explore the impact of adverse drug events (ADE) on readmission in renal transplant recipients and survival of the transplanted kidney.Methods:The hospital information system was searched and medical records of patients who underwent renal transplantation in Beijing Road Medical Area of Xinjiang Military Region General Hospital from January 2008 to December 2018 and were re-admitted at least once (as of December 2020) were collected and analyzed retrospectively. Patient information such as gender, age, weight, ethnicity, kidney transplantation status, postoperative immunosuppressive treatment plan, readmission status, and kidney transplant survival time was extracted and the ADE signals were detected through reviewing the patient re-admission medical history using a self-established global trigger tool. The correlation between ADE and readmission was evaluated by Karch and Lasagna method; patients were included in the ADE-related readmission group (ADE admission group) and the non-ADE-related readmission group (non-ADE admission group) based on the correlation results. The clinical characteristics and the cumulative survival rate of kidney transplants between the 2 groups were compared.Results:A total of 198 patients (1 426 times of readmission) were entered in the analysis, including 154 males and 44 females with an age of 14-62 years, and 118(59.6%) were Han nationality. The immunosuppressive drugs included cyclosporine, tacrolimus, sirolimus, etc. After renal transplantation, 240 times of readmission (16.8%) in 94 patients (47.5%) were associated with ADE. In the ADE readmission group, the number of diagnosed diseases and postoperative readmission times were more and the length of hospital stay was longer than those in the non-ADE readmission group [4 (3,6) vs. 3 (2,5), P=0.001; 6(3, 9) times vs. 4 (2, 8) times, P=0.022; 20(13, 33) days vs. 14 (11, 25) days, P=0.010]. Kaplan-Meier curve showed that the 1-, 3-, 5-, and 10-year cumulative survival rates of kidney transplants were 90.1%, 84.1%, 79.0%, and 57.6% in ADE-related readmission group, which were 99.0%, 94.7%, 90.8%, and 80.4% in non-ADE-related readmission, and the difference was statistically significant ( P=0.001). Conclusions:ADE can increase the readmission times, prolong the length of hospital stay, and reduce the cumulative survival rate of kidney transplants. The monitoring of ADE in renal transplant recipients should be strengthened.

Objective:To investigate the germline mutation status in multi-pathway in Chinese female breast cancer patients and explore their correlation with clinicopathological characteristics. Aim to enrich the database of breast cancer germline gene mutations in Chinese population and provide laboratory evidence for the application of breast cancer targeted drugs.Methods:From January 2017 to July 2019, whole blood samples were collected from 148 women (age of onset concentrated in the 24~80 years old) diagnosed pathologically with breast cancer in the Department of breast surgery, Peking University People′s Hospital. Germline mutations in HR, MMR, BER, and KDR pathway related genes were detected by next-generation sequencing. The pathogenicity interpretation was performed, and pathogenic, likely pathogenic, and mutations of uncertain significance were screened. The clinicopathological characteristics including age at the onset, luminal typing, tumor size, metastasis, and family history were analyzed, and the correlation between mutations in different pathway genes and clinicopathological characteristics was analyzed by the Chi-squared test and Fisher′s exact probability test.Results:Among the 148 patients, there were 69 cases of HR mutations (including three types of mutations, including pathogenic, likely pathogenic and uncertain significance), 16 cases of MMR mutations, 6 cases of BER mutations and 8 cases of KDR mutation. ATM mutations in the HR pathway were associated with luminal typing ( P=0.054), and patients with HER2+breast cancer were more likely to carry ATM mutations. PMS2 mutations in the MMR pathway were correlated with tumor size ( P=0.060), and patients with tumor size>50 mm were more likely to carry PMS2 mutations. KDR mutations was significantly correlated with luminal typing and family history. ( P=0.021, P=0.024). Conclusion:The mutation frequency in BER, KDR, MMR and HR pathways in Chinese breast cancer patients increased successively. Germline mutations in ATM, PMS2 and KDR genes may be involved in the development of breast cancer in the Chinese population. Multi-pathway gene detection of breast cancer can provide laboratory evidence for the use of PARP inhibitors, trastuzumab and other targeted drugs.

Objective:To study the correlation between L-form bacterial infection and surgical site infection (SSI) after laparoscopic cholecystectomy (LC) in patients with chronic calculous cholecystitis, and to find out the interventional measures which can be used in clinical prevention of SSI.Methods:Using a prospective nested case-control study, patients with chronic calculous cholecystitis who underwent LC at the Third Affiliated Hospital of Guizhou Medical University from September 2016 to June 2020 were prospectively studied. The postoperative follow-up observation time was within 1 month from the date of surgery. The patients’ general information, perioperative conditions, presence of L-form bacteria in gallbladder contents, postoperative SSI and other indicators, as well as the data entered by the surgeons before the operations were collected in detail. According to whether SSI occurred or not after operation, these patients were paired and grouped in a ratio of 1∶4 between the SSI group versus the control group. Multivariate logistic regression analysis was used to determine the risk factors for SSI after LC.Results:Of 695 patients included in the study, there were 248 males and 447 females, aged (46.0±15.0) years old. The infection rates of L-form bacteria in the case group and the control group were 45.32% and 30.94%, respectively. The infection rate of L-form bacteria in the case group was significantly higher than that in the control group ( P<0.05). The L-form bacterial infection rate ( OR=2.082, 95% CI: 1.335-3.197, P=0.001) suggested that L-form bacterial infection significantly increased the risk of SSI. In addition, rupture of gallbladder during surgery, ( OR=2.249, 95% CI: 1.352-3.740, P=0.002), adhesion of gallbladder to surrounding tissues ( OR=1.903, 95% CI: 1.133-3.194, P=0.015), and excessive bleeding during operation ( OR=2.247, 95% CI: 1.418-3.561, P=0.001) also increased the risk of SSI, while increased experience of operating surgeons on number of surgical cases ( OR=0.549, 95% CI: 0.340-0.888, P=0.014) decreased the risk of SSI. Conclusion:L-form bacterial infection was one of the risk factors of SSI. L-form bacterial culture and tests for drug sensitivity were important in selecting antibiotics. Improved surgical skills, careful dissection of gallbladder from surrounding adhesions, reduction on intraoperative blood loss and avoiding gallbladder rupture contributed to a decrease in SSI.

Objective:To analyze the related factors for plural bacterial infection in elderly patients with health care-associated pneumonia(HCAP), in order to provide the reference for clinical practice.Methods:A total of the 1 012 elderly patients conforming to inclusion criteria were in the age of 60-87(70.7±6.2)years, with 431 cases of males and 581 cases of females.The clinical data of elderly patients with HCAP admitted to our hospital from February 2015 to December 2018 were collected.According to the number of infected bacteria category, the patients were divided into the single bacterial infection group and the plural bacterial infection group.The distribution of pathogens was compared between the two groups, and the related factors for plural bacterial infection were analyzed.Results:There were 122 HCAP cases in the plural bacterial infection group, with 286 strains of pathogenic bacteria detected, while 890 HCAP cases were found in the single bacterial infection group, with 890 strains of pathogenic bacteria detected.Compared with the single infection group, the plural bacteria infection group showed that the proportions of Gram-positive Staphylococcus aureus and Enterococcus faecium were increased, while the proportion of Staphylococcus epidermidis was relatively decline( χ2=11.086, 8.460 and 4.056, P=0.001, 0.004 and 0.044). The proportions of Gram-negative Pseudomonas aeruginosa and Stenotrophomonas maltophilia were higher, while the proportions of Escherichia coli and Klebsiella were lower in the plural bacteria infection group than in the single bacteria infection group( χ2=7.495, 4.918, 9.011 and 4.604, P=0.006, 0.027, 0.003 and 0.032). Multivariate Logistic regression analysis showed that the independent risk factors for plural bacteria infection in elderly HCAP patients were the combined use of antibiotics within 30 days(≥3 kinds), more chronic underlying diseases(≥2 kinds), pneumonia severity index(PSI)classification being high, longer hospitalization time within 90 days(≥15 days), a history of ICU stays within 90 days, age(≥70 years old)( OR=2.389, 1.840, 1.289, 1.877, 2.089 and 1.981, P=0.001, 0.003, 0.001, 0.002, 0.001 and 0.002, respectively). Conclusions:The plural bacteria infection in elderly HCAP patients is related to many factors.The effective measure to reduce the plural bacteria infection in elderly HCAP patients are to focus on patients with severe disease, more basic diseases and advanced age, and on the shortening of the unnecessary hospitalization time, the reducing of the time of ICU stays, the reasonably selecting of antibiotics, the reducing of the unnecessary combination of antibacterial drugs.

Malignant middle cerebral artery infarction (mMCAI) is a critically ill neurological disease, which often leads to the rapid deterioration of neurological function, resulting in consciousness disturbance and even death. Therefore, early identification and judgment of mMCAI to determine the need for lateral craniectomy decompression is essential to improve the survival rate of patients. With the development of neuroimaging technology, some CT and MRI parameters have been able to predict mMCAI. This article reviews the predictive value of CT and MR related parameters to mMCAI.

Objective To study the clinical manifestations and antibiotic sensitivity features of early-and late-onset invasive infections caused by group B Streptococcus (GBS). Methods A total of 96 infants with invasive GBS infections were enrolled prospectively from seven tertiary hospitals of GBS Infection Research Cooperative Group in southwest Fujian, such as Xiamen Maternal and Child Care Hospital, etc., from January 2016 to June 2018. According to the onset time of infection after birth, they were divided into early-onset GBS disease (GBS-EOD) group (<7 d, n=67) and the late-onset GBS disease (GBS-LOD) group (7-89 d, n=29). Clinical manifestations, disease spectrum, complications and outcomes of the two groups were compared. Drug sensitivity test was carried out using disk diffusion test. Chi-square or Fisher's exact test, two independent sample t-test or Mann-Whitney U tests were used for statistical analysis. Results (1) The average ages at onset in GBS-EOD and GBS-LOD groups were (15.8±6.7) h (0.5-142.0 h) and (25.0±8.1) d (9-89 d), respectively. The incidence of tachypnea, pallor, fever and convulsion were noted in 68.7% (46/67) vs 44.8% (13/29), 52.2% (35/67) vs 17.2% (5/29), 23.9% (16/67) vs 65.5% (19/29) and 7.5% (5/67) vs 48.3% (14/29) of GBS-EOD and GBS-LOD groups with χ2 values of 6.282, 10.199, 15.146 and 21.237 (all P<0.05). The main clinical manifestations of GBS-EOD were tachypnea and pallor, while most of the patients in the GBS-LOD group developed fever and convulsions. (2) The incidence of pneumonia, sepsis, meningitis, sepsis complicated by septic joints, pneumonia complicated by sepsis, sepsis complicated by meningitis and pneumonia complicated by sepsis and meningitis were noted in 43.3% (29/67) vs 20.7% (6/29), 9.0% (6/67) vs 17.2% (5/29), 0.0% (0/67) vs 3.4% (1/29), 0.0% (0/67) vs 6.9% (2/29), 31.3% (21/67) vs 13.8% (4/29), 6.0% (4/67) vs 31.0% (9/29) and 10.4% (7/67) vs 6.9% (2/29) of GBS-EOD and GBS-LOD groups. There was a statistically significant difference in the disease spectrum between the two groups (Fisher's exact test, all P<0.001). Compared with the GBS-LOD group, the GBS-EOD group had a higher incidence of pneumonia [85.1% (57/67) vs 41.4% (12/29), χ2=19.116, P<0.001] and a lower incidence of meningitis [16.4% (11/67) vs 41.4% (12/29), χ2=6.922, P=0.009]. Complications such as acute respiratory distress syndrome (ARDS), pulmonary hemorrhage, shock and persistent pulmonary hypertension of the newborn (PPHN) occurred much more in the GBS-EOD group than the GBS-LOD group [28.4% (19/67) vs 6.9% (2/29), 13.4% (9/67) vs 0.0% (0/29), 11.9% (8/67) vs 10.3% (3/29), 4.5% (3/67) vs 0.0% (0/29), χ2=13.683, P<0.001]. (3) Among the 96 patients, 23 (24.0%) had meningitis and 73 (76.0%) developed pneumonia and sepsis. Meningitis resulted in a higher fatality rate [17.4% (4/23) vs 4.1% (3/73), χ2=4.564, P=0.035] and longer average hospital stay [(37.2±12.6) vs (14.1±5.3) d, t=7.831, P<0.001] than pneumonia and sepsis. Seven out of the 19 meningitis survivors developed intracranial complications. (4) The overall fatality rate in this study was 7.3% (7/96) and no significant difference was found between GBS-EOD and GBS-LOD group [7.5% (5/67) vs 6.9% (2/29), χ2=0.010, P=0.982]. Among the 67 GBS-EOD infants, 58 (86.6%) occurred within 24 h and five of them died, but no death was reported in the other nine cases occurred after 24 h. (5) Totally 96 strains of GBS were isolated with 100% sensitivity to penicillin, ampicillin, cefazolin and meropenem, and 97% to vancomycin. Around 79.3%-91.0% of GBS isolates were resistant to clindamycin and erythromycin. Conclusions Clinial features vary greatly in GBS-LOD and GBS-EOD cases. Infants with meningitis have poor prognosis. The drug resistance rate of GBS to erythromycin and clindamycin are relatively high.