SoxR, one of bacterial transcriptional regulators, plays a crucial role in bacterial responses to oxidative stress induced by unfavorable environmental conditions. So far, the understanding of bacterial responses to oxidative stress mainly stems from a handful model bacteria such as Escherichia coli and the studies on non-model bacterial responses to oxidative stress are limited. In this study, Citrobacter braakii JPG1, a commonly occurring strain of enterobacteria, was used as a model for the first time to explore the role of SoxR in the responses to aerobic/anaerobic-menadione stress. First, we analyzed the phylogenetic relationship of SoxR based on the whole genome and constructed the soxR-deleted strain (ΔsoxR). Then, the cell counts of the wild type (WT) and ΔsoxR were compared under aerobic/anaerobic-menadione stress. The results showed that the cell count of WT exposed to the aerobic-low concentration menadione (0.1 mmol/L) stress for 24 h increased by 4.2 times compared with that at the time point of 0 h, while that of ΔsoxR only increased by 1.3 times. The vast majority of WT and ΔsoxR cells died after exposure to the aerobic-high concentration menadione (0.3 mmol/L) stress for 24 h, with the cell counts only 29% and 0.2% of those at the time point of 0 h, respectively. Interestingly, the cell counts of WT showed no significant difference between the anaerobic-menadione stress and the control (P > 0.05), and the same was true for ΔsoxR. All these results indicated that SoxR of C. braakii JPG1 only has a regulatory effect on the redox cycling compound menadione under aerobic conditions and enhance the antioxidant capacity. Under anaerobic conditions, menadione failed to activate SoxR. The findings from this study provide new insights into understanding both the physiological responses to menadione stress and the regulatory role of SoxR under different oxygen conditions.
Bacterial Proteins/physiology* ; Anaerobiosis ; Aerobiosis ; Vitamin K 3/pharmacology* ; Citrobacter/metabolism* ; Transcription Factors/physiology* ; Oxidative Stress ; Gene Expression Regulation, Bacterial

Objective:To investigate the clinicopathological characteristics and genetic mutations of SMARCA4-deficient lung adenocarcinoma.Methods:From January 2021 to April 2023 in the First Affiliated Hospital of Zhengzhou University, 42 cases of SMARCA4-deficienct lung adenocarcinoma were diagnosed and now analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed. Next-generation sequencing (NGS) was performed to investigate the mutations of related genes.Results:Among the 42 cases, there were 35 biopsy and 7 surgical specimens. There were 38 males and 4 females. The male to female ratio was 9.5∶1.0, with an age range from 42 to 78 years. Thirty-three patients were smokers. Overall, 4 cases (9.5%), 2 cases (4.7%), 18 cases (42.9%) and 18 cases (42.9%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Microscopically, all the cases were non-mucinous adenocarcinoma, without lepidic pattern. The morphology was diverse. Rhabdomyoid cells, tumor giant cells and tumor necrosis were present. Most of the tumor cells had eosinophilic cytoplasm and occasionally clear cytoplasm. Defined cell borders and variable cytoplasmic hyaline secretory globules could be found. Inflammatory cells infiltrated the tumor stroma. Immunohistochemistry showed 29 cases (69.0%, 29/42) expressed TTF1, 10 cases (40.0%, 10/25) expressed Napsin A, and 20 cases (100.0%, 20/20) expressed INI1. Forty cases (95.2%, 40/42) showed BRG1 loss in all tumor cells, while 2 cases (4.8%, 2/42) had partial BRG1 loss. PD-L1 (22C3) was positive in 59.2% of the cases (16/27). NGS revealed mutations in EGFR, ROS1, MET, RET and KRAS. Six cases (6/8) showed SMARCA4 mutation, while some cases were accompanied by mutations of TP53 (7/15), STK11 (4/8), and KEAP1 (1/8). Driver gene mutations were more common in women ( P<0.05). Patients were followed up for 1-25 months. Four patients died and 20 patients′ diseases progressed. Conclusions:SMARCA4-deficient lung adenocarcinoma lacks characteristic morphology. Most of them express TTF1 and harbor driver gene mutations. It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.

Objective:To investigate the efficacy and safety of en-bloc Holmium laser enucleation of the prostate (HoLEP) with an early apical mucosa dissection technique for the treatment of benign prostate hyperplasia (BPH).Methods:The clinical data of 215 patients treated with HoLEP for BPH from January 2020 to January 2023 in the Department of Urology, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. According to different treatment methods, the patients were divided into study group ( n=112) and control group ( n=103). Patients in the study group were treated by the en-bloc HoLEP with an early apical mucosa dissection technique, while patients in the control group were treated by the classical two or three-lobes HoLEP. The primary endpoints included the rates of urinary incontinence at 1-month, 3-month, and 6-month after surgery in two groups of patients. The secondary endpoints included operative time, hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay, and international prostate symptom score (IPSS), quality of life (QoL), Qmax, and postvoid residual urine (PVR) at 3-month and 6-month after surgery. The measurement data were tested by Shapiro-Wilk normality test. The normal distribution of the measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between two groups. Measurement data of skewness distribution were expressed as median (interquartile distance) [ M( Q1, Q3)], and Wilcoxon or Mann-Whitney U test were used for comparison between two groups. The count data in the two groups were compared by the Chi-square test. Results:The incidence of urinary incontinence in the study group was 9.0% (10/112) and 3.6% (4/112) at 1-month and 3-month after surgery, which was significantly lower than those in the control group [18.5% (19/103) and 11.7% (12/103)], and the differences were statistically significant ( P< 0.05). Urinary incontinence in two groups recovered completely 6-month after surgery. The operation time of the study group was (68.74±23.71) min, which was lower than that of the control group [(88.04±25.43) min], and the difference was statistically significant ( P<0.05). There were no significant differences in hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay in the two groups ( P> 0.05). The IPSS, QoL, Qmax and PVR of the two groups were significantly improved at 3-month and 6-month after surgery ( P< 0.05), but there was no significant difference between the two groups ( P> 0.05). Conclusion:En-bloc HoLEP with an early apical mucosa dissection technique is safe and reliable in treating BPH, and has advantages over classic HoLEP in terms of short-term urinary continence rates, shortening operation time.

OBJECTIVE To screen the prescription and preparation method of Bupleurum nanoemulsion, and evaluate its quality, study the antipyretic effect. METHODS The emulsifier and co-emulsifier of the nanoemulsion were preliminarily screened, and then the prescription was screened by pseudo-ternary phase diagram. The quality evaluation of the appearance, particle size distribution, structure type, stability and content of the prepared Bupleurum nanoemulsion was performed. Wistar rats were further randomly divided into blank control group, model control group, positive control group(aspirin group), Bupleurum nanoemulsion high-dose, medium-dose and low-dose groups(18.00, 9.00, 3.00 g·kg−1). Except for the blank control group, the pathological model of fever rats was prepared in the other groups. According to the scheduled experimental requirements, rats in each group were given the corresponding drugs. And the temperature changes of rats in each group were recorded at 0.5, 1, 1.5, 2, 3 h to observe the antipyretic effect of Bupleurum nanoemulsion. RESULTS The best prescription of Bupleurum nanoemulsion: Tween-80 6 g and n-butanol 3 g, Bupleurum extract dissolved in pure water as water phase 20 mL, Bupleurum oil as oil phase 2 g. At room temperature, the Bupleurum nanoemulsion was a yellow-brown clear and transparent liquid, O/W nanoemulsion, with an average particle size of (77.21±3.66)nm, polydispersity index of 0.28±0.04, Zeta potential of (–18.81±1.42)mV, and saikosaponin content of 3.071 mg·mL−1, with good stability. In animal experiments, compared with the model control group, the rectal temperature of aspirin group and Bupleurum nanoemulsion high-dose group was significantly lower after the first administration(P<0.01), the rectal temperature of Bupleurum nanoemulsion middle-dose group was significantly lower after the first administration 2, 3 h(P<0.01). CONCLUSION The Bupleurum nanoemulsion is transparent and stable, and it has good antipyretic effect on fever rat model.

OBJECTIVE To study the efficacy of sinapine thiocyanate dissoluble microneedle （ST-DMN） for acupoint administration against bronchial asthma （BA）. METHODS The network pharmacology and molecular docking techniques were used to screen the core targets of sinapine thiocyanate （ST） against BA， and the pharmacodynamics of the top 3 core targets was studied. Firstly， ST-DMN was prepared （drug loading of ST was 1 mg/tablet）； secondly， 30 rats were divided into blank control group， model control group， blank microneedle group， Sinapine powder plaster group （positive control group） and ST-DMN group. Except for the blank control group， rats of other groups were sensitized with 10% ovalbumin （containing aluminum hydroxide adjuvant） and nebulized with 1% ovalbumin to induce the BA model. After modeling， blank control group did not receive any intervention； normal saline was applied to the Feishu acupoint and Dazhui acupoint of the rats in the model control group， while the blank microneedle group， Sinapine powder plaster group and ST-DMN group were given blank microneedle， Sinapis alba powder （plaster， 1.5 g） and ST-DMN （3 tablets at 2 acupoints） at same acupoint， once a day， for 28 consecutive days. After administration， the general symptoms were observed and the body mass of the rats was measured.pathological changes of lung tissues in rats was observed； the levels of prostaglandin endoperoxide synthase 2 （PTGS2）， GNYL matrix metalloproteinase-9 （MMP-9） and interleukin-2 （IL-2）in serum， bronchoalveolar lavage fluid （BALF） and lung tissues were determined. RESULTS Results of network pharmacology and molecular docking showed that the key targets of ST against BA were identified as PTGS2， MMP-9， IL-2， epidermal growth factor receptor， heat shock protein90AA1， etc. Pharmacodynamic experiments showed that compared with model control group， relieved cough， restored hair color， sensitive behavior， stable respiration and increased body weight were all found in ST-DMN group； the histopathological changes as the structure of lung tissue， infiltration of alveolar epithelial cells and pulmonary interstitial inflammatory cells were improved to different extent； the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The anti-BA effect of ST-DMN acupoint administration is good， the mechanism of which may be associated with decreasing the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue.

Objective:To investigate the safety and efficacy of individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI.Method:The clinical data of patients undergoing prostate biopsy in Beijing Friendship Hospital from December 2018 to November 2021 were analyzed retrospectively . A total of 228 patients with a median age of 65(49-83)years underwent biopsy. There were 102(44.7%) with tPSA <10 ng / ml, 108(47.4%) with tPSA 10-20 ng /ml, and 18(7.9%) with tPSA >20 ng /ml, with the median tPSA of 9.87(4.1-89.0)ng /ml. There were 42(18.4%) cases without MRI results, and 32(14.0%)cases with PI-RADS score of 1-2, 47(20.6%)cases of PI-RADS 3, 66(28.9%)cases of PI-RADS 4 and 41(18.1%)cases of PI-RADS 5, respectively.Transrectal ultrasound-guided transperineal prostate targeted biopsy (TB) and systematic biopsy (SB) were performed under local anesthesia or intravenous anesthesia. SB was performed for those without MRI and PI-RADS score of 1-2 (SB group), and TB and SB were performed for those with PI-RADS score of 3-5 (TB+ SB group). Prostate image under ultrasound was cognitively fused according to PI-RADS v2. One needle per area was distributed in 10 areas of each layer(the transition zone anterior and posterior sectors, the peripheral zone anterior, lateral, and medial sectors or central zone in left and right lobe). For those whose prostate length was less than 3cm, 10 needles were punctured, and two needles were added to each lateral lobe of the apex with a total of 14 needles. For those whose prostate length was from 3 to 6 cm, selected two layers with a total of 20 needles. For those with a length greater than 6cm, selected three layers with a total of 30 needles. If there was a suspicious lesion with PI-RADS score of 3-5, two needles were targeted for each lesion.The detection rate and complication rate of prostate cancer and clinically significant prostate cancer (csPCa) in the overall samples were observed, and the difference of the detection rate of prostate cancer and csPCa between the two groups was compared.Results:Of the 228 cases, there were 46 cases undergoing biopsy of one layer, 148 cases of two layers, and 34 cases of three layers, detecting 131 prostate cancer (PCa) diagnosed by pathology, with a detection rate of 57.5%, including 40 cases (17.5%)of clinically insignificant PCa and 91 cases(39.9%)of csPCa. The detection rate of PCa in TB+ SB group was 61.0%(94/154), which was higher than that in SB group, but there was no significant difference ( P=0.114). However, the detection rate of csPCa in TB + SB group was higher than that in SB group, which was 46.8%(72/154)vs. 25.6%(19/74), respectively ( P=0.002). In the combined TB and SB group (TB + SB group), the detection rate of csPCa by TB was 44.8% (69/154), which was higher than that of 33.8%(52/154)by SB( P=0.047). In the TB+ SB group, 7(4.5%) PCa were missed by SB, which was less than 18 cases (11.7%) missed by TB( P=0.022), but csPCa were missed by SB more than that missed by TB( P<0.001). There were 37 cases suffered from complications, with Clavien Dindo classification grade 1 of 29 cases (12.7%), grade 2 of 7 cases (3.1%), and grade 3 of 1 case(0.4%). Conclusions:Individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI is safe and reliable. Target biopsy by cognitive fusion can improve the detection rate of significant PCa. Systematic biopsy is also an important and essential supplement, which can detect prostate cancer missed by TB. Combined TB and SB are the best choice.

Objective:To investigate the clinical characteristics and prognosis of Epstein-Barr virus-related diseases in adults.Methods:The clinical data of 59 patients with Epstein-Barr virus-related diseases in Huashan Hospital, Fudan University, Shanghai from January 2017 to August 2019 were analyzed retrospectively. The clinical manifestations of patients with infectious mononucleosis (IM), chronic active Epstein-Barr virus infection (CAEBV) and lymphoma in patients were compared. Patients were divided into acute course group (IM) and chronic course group (CAEBV+ lymphoma), and the results of labratory indications (blood rontine, liver function, imflammatory indications, Epstein-Barr virus DNA, Epstein-Barr virus antibody and T lymphocyte) were compared between two groups. Statistical analysis was performed by Mann-Whitney U test, chi-square test or Fisher exact probability test. Results:Among the 59 patients, 23 cases (39.0%) were diagnosed with IM, 23 cases (39.0%) were lymphoma and 13 cases (22.0%) were CAEBV. The clinical manifestations of patients with Epstein-Barr virus-related diseases were fever (57/59, 96.6%), lymphadenopathy (37/59, 62.7%) and splenomegaly (36/59, 61.0%). There were 17 patients in the chronic course group experienced hemophagocytic lymphohistiocytosis (HLH). The white blood cell counts, hemoglobin levels and platelet counts of patients in the chronic course group (4.07(1.94, 8.35)×10 9/L, 89.5(74.5, 108.0) g/L and 100(37, 161)×10 9/L, respectively) were all lower than those in the acute course group (9.91(6.75, 17.38)×10 9/L, 132.5(118.2, 152.0) g/L and 197(129, 233)×10 9/L, respectively), with statistically significant differences ( U=3.69, 5.22 and 3.61, respectively, all P<0.01). The levels of procalcitonin, C-reactive protein and serum ferritin in the chronic course group (0.45(0.15, 1.13) μg/L, 47.75(17.57, 84.67) mg/L and 2 000(682, 2 002) μg/L, respectively) were all higher than those in the acute course group (0.12(0.07, 0.28) μg/L, 6.39(3.13, 11.38) mg/L and 482(159, 1 271) μg/L, respectively), with statistically significant differences ( U=-2.95, -3.77 and -4.16, respectively, all P<0.01). The counts of CD4 + T lymphocytes, CD8 + T lymphocytes, CD19 + B lymphocytes and natural killer cells in the chronic course group (259.15(101.98, 509.26), 214.69(119.31, 529.47), 46.14(4.44, 135.87) and 81.09(41.53, 118.46)/μL, respectively) were all lower than those in the acute course group (738.88(592.20, 893.94), 1 609.17(920.88, 3 952.34), 144.52(83.65, 215.14) and 309.82(123.78, 590.68)/μL, respectively), with statistically significant differences ( U=3.66, 3.80, 2.90 and 3.40, respectively, all P<0.01), while the CD4 + /CD8 + T lymphocytes ratio in the chronic course group was higher (0.90(0.60, 1.70) vs 0.45(0.10, 1.28))( U=-2.29, P=0.02). Twenty-three patients with IM were all cured, while 10 patients with lymphoma died and 13 received chemotherapy. Seven patients with CAEBV died and six improved. Conclusions:The clinical characteristics of Epstein-Barr virus-related diseases in adults are fever, lymphadenectasis, splenomegaly.Chronic Epstein-Barr virus infection may be associated with HLH. The prognosis of adults with acute Epstein-Barr virus infection is good, while that of long-term chronic Epstein-Barr virus infection is poor.

Objective To investigate the incidence,bacterial pathogen and risk factors of bacterial meningitis after major craniotomy.Methods Clinical data of patients who underwent at least one craniotomy in Huashan Hospital Affiliated to Fudan University in 2008 were collected.All subjects were ≥ 18 years old,and survived at least 7 days after surgery.Patients with only cerebrospinal fluid drainage,burr holes,cranioplasty,vascular interventional surgery,transsphenoidal or spinal surgery were excluded.Risk factors for bacterial meningitis after major craniotomy were analyzed by Logistic regression.Results A total of 691 patients were enrolled,in 60 of whom (8.68％) bacterial meningitis was identified.Among 44 samples,5 were positive in culture with 2 of Acinetobacter baumannii,1 of Enterococcus faecalis,1 of Streptococcus intermedius and 1 of Klebsiella pneumonia.Diabetes (OR =5.79,95％ CI:1.40-23.93,P =0.02),Glasgow Coma Scale score ＜ 12 (OR =6.56,95％ CI:1.17-36.80,P =0.03),external ventricular drainage (OR =4.31,95％ CI:1.57-11.82,P =0.01),and continuous lumbar cistern drainage (OR =22.82,95％ CI:10.31-50.52,P =0.00) were independent risk factors for bacterial meningitis after major craniotomy.Patients with external ventricular drainage ＞ 7 d were 11.82 times more likely to develop bacterial meningitis,and those with continuous lumbar cistern drainage ＞ 10 d were 25.50 times more likely to develop bacterial meningitis.Conclusions Bacterial meningitis remains a common complication after major craniotomy,and most are induced by Gram-negative bacilli.Diabetes,Glasgow Coma Scale score,external ventricular drainage and continuous lumbar cistern drainage may increase its incidence.

Objective To evaluate the performance of peripheral blood T-SPOT.TB and cerebrospinal fluid (CSF) interferon (IFN)-γ detection in the diagnosis of tuberculous meningitis (TBM).Methods Among the 182 consecutive cases with suspected TBM in Huashan Hospital from March 2011 to March 2013,30 patients were included in the case group according to the latest diagnostic criteria of TBM.Thirty-nine patients diagnosed with non-tuberculous meningitis were included in the control group.T-SPOT.TB was employed to detect tuberculosis-specific IFN-γ-secreting T cells in the peripheral blood.And IFN-γ in CSF was detected simultaneously by enzyme-linked immunosorbent assay (ELISA) without antigen stimulation.The CSF was collected from 10 patients of TBM group after anti tuberculosis treatment for 4 weeks to observe the dynamic changes.The t-test was used for analysis of continuous variables with normal distribution and Kruskal-Wallis test was used for analysis of variables with abnormal distribution.Results ()f the 30 TBM cases,6 were confirmed cases and 24 were highly suspected cases.The control group was comprised of 12 viral encephalitis,16 suppurative meningitis and 11 cryptococcal meningitis.The positive rate of T-SPOT.TB was significantly higher in TBM group compared with control group (70％ vs 13％,x2 =12.15,P＜0.01).The mean concentration of CSF IFN γ of TBM group was 244.35 pg/mL,which was significantly higher than that of control group 9.48 pg/mL (Z=-4.646,P＜0.01).The CSF IFN-γ was significantly decreased after 4 weeks of treatment (271.02 pg/mL vs 81.36 pg/mL,Z=-3.099,P=0.002).The sensitivity and specificity of peripheral blood T-SPOT.TB in the diagnosis of TBM were 70％ and 87％,respectively.The area under the receiver operating characteristic (ROC) curve of CSF IFN-γ for TBM diagnosis was 0.819; the optimal cut-off point was 81.36 pg/mL; the corresponding sensitivity and specificity were 83 ％ and 85 ％,respectively.Conclusion Both the detection of peripheral blood T-SPOT.TB and CSF IFN-γ are of great importance for the diagnosis of TBM.Dynamic observation of CSF IFN-γ is important for disease monitoring.

Objective To analyse the clinical feature of infective endocarditis (IE) in recent years.Methods Clinical profiles including age of onset,predisposing factor,clinical manifestation,blood culture and ultrasonic cardio gram (UCG) of 97 cases from Huashan Hospital in the recent 10 years were collected and analyzed retrospectively. Descriptive data were represented as mean ±standard deviation form.Positive rate was represented as percentage form.Fisher's exact test were used to determine two groups' comparison.Results The mean age of the population was (49±17)years.Seventy-three patients (75.3％) had background heart disease,the top 3 of which was rheumatic heart disease in 27 patients (27.8％),congenital heart disease in 23 patients (23.7％) and idiopathic mitral valve prolapse in 18 patients (18.6 ％).The most common clinical manifestation were fever (99.0％),murmurs (95.9％) and anemia (84.5％).Sixty-six patients (68.0％) had positive result of blood cultures. Streptococcus viridans,which was found in 28 patients with native valve endocarditis (42.4 ％),was still the most common pathogen.Staphylococcus,which was found in 18patients (27.3％),had an elevated ratio.Staphylococcus aureus was found in 10 patients (15.2％)and 3 of which were MRSA.Coagulase-negative staphylococcus was found in 8 patients (12.1 ％ ) and 2 of which were MRCNS. Drug-resistant bacteria was increased and pathogens were varied.Vegetations were found in 79 patients (81.4％) by UCG.ConclusionsClinical manifestation,predisposing factor and pathogen have changed in IE patients. Attaching importance to physical examination,multiple-time blood culture and UCG helps the diagnose of IE.