Inhibitory Effect of Sesquiterpenoid M36 from Myrrha on Growth of Human Hepatoma Cells / 中国实验方剂学杂志

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC50） value of M36 for 48 h was 5.03 μmol·L-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Anti-infection treatment and pharmaceutical care for a patient with severe pneumonia caused by Chlamydia psittaci / 中国药房

OBJECTIVE To provide ideas and reference for the anti-infection treatment and pharmaceutical care for severe pneumonia caused by Chlamydia psittaci. METHODS Clinical pharmacists participated in the whole process of the treatment for a patient with C. psittaci-induced severe pneumonia. According to the patient’s medical history， clinical symptoms and test results， clinical pharmacists assisted the physician to dynamically adjust the anti-infective scheme； for C. psittaci infection， the patient was treated with tigecycline combined with azithromycin successively， and other infection therapy plans were dynamically adjusted according to the results of pathogen examination. During the treatment， the patient suffered from suspicious adverse drug reactions such as prolonged QTc interval， elevated lipase and amylase； the clinical pharmacists conducted pharmaceutical care and put forward reasonable suggestions. RESULTS The physician adopted the pharmacists’ suggestion， and the patient was discharged after treatment. CONCLUSIONS For the treatment of severe pneumonia caused by C. psittaci， the characteristics of patients， drugs and pathogens should be taken into account to develop individualized anti-infective treatment. Tetracyclines and macrolides have a definite effect on C. psittaci infection， but attention should be paid to the possible ADR caused by drugs in clinical application.

Analysis of 111 cases of aristolochic acids nephropathy / 药学实践杂志

Objective To analyze the clinical characteristics and regularity of aristolochic acid nephropathy (AAN) induced by drugs containing aristolochic acid. Methods The clinical data of 111 patients with AAN induced by aristolochic acid were reviewed. The clinical features, medication and treatment of AAN were analyzed. Results Among 111 patients, there were more females than males (2.58∶1), 101 cases (90.99%) were over 50 years old； the mean age was (63.70±11.67) years old;the average duration of medication was (8.08±6.94) years. The drugs involved were Guanxinsuhe pill and Longdanxiegan pill in 106 cases (95.50%). Serum creatinine increased in 108 cases, urea nitrogen increased in 106 cases and hemoglobin decreased in 103 cases, most of which were hypogravity urine, mild to moderate proteinuria and occult blood. Ultrasonic examination revealed that the kidneys were damaged to varying degrees. Pathological biopsy of kidney showed renal tubular damage. Most patients had an insidious onset and varying degrees of progression, which were not proportional to the age and the duration of taking the medicine. In clinical, the renal function was progressively damaged, most of which were irreversible and with a poor prognosis. Conclusion Patients with renal impairment differed greatly individually, and the renal damage was not paralleled with the medication duration and dose of drugs containing aristolochic acid.AAN progressed rapidly, and the disease still progressed even after stopping taking drugs containing aristolochic acid. Strengthening pharmacovigilance, implementing early diagnosis and effective intervention could help to reduce the occurrence of AAN and attenuate its development.

Comparing the predictive value of parameters extracted from circular ROIs with whole liver histogram on Gd-EOB-DTPA enhanced MRI for postoperative liver failure in focal liver lesions / 中华肝胆外科杂志

Objective:To compare the predictive value of parameters extracted from circular region-of-interest (ROI) with whole-liver histogram on gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced T 1 map for postoperative liver failure in patients with liver focal lesions. Methods:The data of patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions in Zhongshan Hospital, Fudan University from March 2016 to March 2018 were analyzed retrospectively. Forty patients were enrolled, including 30 males and 10 females, aged (56.6±12.1) years. According to the occurrence of postoperative liver failure, forty patients were divided into liver failure group ( n=14) and control group ( n=26). The parameters extracted from circular ROIs and whole liver histogram on T 1 map before Gd-EOB-DTPA enhancement and in hepatobiliary phase (HBP) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of these parameters in predicting postoperative liver failure. Results:The mean, standard deviation, median and 95% quantile of T 1 HBP in histogram parameters of liver failure group were significantly higher than those of control group (all P<0.05). The three parameters extracted from circular ROIs were not effective in predicting liver failure after hepatectomy (all P>0.05). Among all the liver histogram parameters, the area under the ROC curve of the 95% quantile before T 1 enhancement for predicting postoperative liver failure was 0.702 (95% CI: 0.523-0.881), the standard deviation of T 1 HBP was 0.739 (95% CI: 0.568-0.910), and the 95% quantile of T 1 HBP was 0.721 (95% CI: 0.540-0.903). The predictive efficacy were good (all P<0.05). Among them, the predictive performance of T 1 HBP standard deviation was the best, the area under the ROC curve was 0.739, the sensitivity was 85.7%, the specificity was 57.7%, and the best threshold was 54.8 ms. Conclusions:When Gd-EOB-DTPA enhanced T 1 mapping is used to predict postoperative liver failure in patients with focal liver lesions, the whole-liver histogram analysis is superior to the conventional circular ROI-based statistical method.

Dose comparison of mammography with two photographic modes / 中华放射医学与防护杂志

Objective:To compare radiation dose between digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM), and explore the correlation of average glandular dose(AGD) with breast density and compression thickness.Methods:The mammographic data of patients with breast diseases who underwent digital breast tomosynthesis (DBT) and the population who underwent full-field digital mammography (FFDM) screening in the First Affiliated Hospital of Kunming Medical University from October 2020 to May 2022 were retrospectively collected. The compression thickness, compression force and AGD were recorded. According to the 2013 ACR BI-RADS MAMMOGRAPHY, the breast gland density was classified into 4 types: a(glandular tissue<25%), b(glandular tissue 25%~50%), c(glandular tissue 50%~75%) and d(glandular tissue >75%), by two senior doctors engaged in breast imaging diagnosis. The relationships between different gland densities, different compression thicknesses and AGD under FFDM and DBT mode were analyzed.Results:In both FFDM and DBT modes, the AGD increased significantly with the increase of breast density( F=861.63, 617.83, 330.33, 451.45, 290.47, P<0.001), and AGD a<AGD b<AGD c<AGD d. For type c and d breasts undergoing FFDM, AGD was lowest when the compression thickness was 31~40 mm. Under the same compression thickness, The AGD DBT was significantly higher than the AGD FFDMin all types (Type a: t=-17.88, -42.19, -29.90, -28.14, -24.95, P<0.001; Type b: t=-49.18, -35.94, -27.25, -28.37, -24.10, P<0.001; Type c: t=-11.78, -32.90, -23.13, -20.51, -18.24, P<0.001; Type d: t=-7.94, -26.24, -17.24, -15.44, -13.81, P<0.001). The difference between two AGDs of Type d with compression thickness of 61~70 mm was the largest, which was 1.07 mGy (95% CI: 0.92~1.22). The AGD was positively correlated with breast density and compression thickness, and the relationship of FFDM was stronger than that of DBT. Conclusions:The AGD is positively correlated with breast density and compression thickness in mammography. Compared with FFDM, DBT can increase AGD, The AGD would increase in DBT than FFDM but be safe. DBT would be beneficial to patients with breast diseases in clinical practice.

Research progress in the diagnosis and treatment of the glenoid fractures / 中华创伤骨科杂志

The anatomy of the shoulder joint is complex. Glenoid fractures, intra-articular fractures of the shoulder, are relatively rare and often accompanied by serious injury. At present, there has been no consensus on the optimal strategies for their treatment. Insufficient knowledge and improper treatment of the surgeons may seriously affect the shoulder function of the patients to harm their quality of life. Therefore, proper handling of such fractures is a major challenge in clinic. In recent years when high-energy injuries are increasing and functional recovery after shoulder fracture is emphasized by more and more patients, great efforts have been put into the research into such fractures by orthopedic surgeons. This reviews expounds on the anatomy, diagnosis, classification and treatment of glenoid fractures, aiming to provide useful reference for the orthopaedic surgeons who deal with glenoid fractures.

The chain mediating role of hostile cognition and anger between dark triad and college students' cyberbullying / 中华行为医学与脑科学杂志

Objective:To explore the chain mediating effects of hostile cognition and anger between dark triad and college students' cyberbullying.Methods:From May to July 2022, a total of 1 316 college students from four universities completed a cross-section questionnaire survey including the dirty dozen (DD), the cyberbullying subscale of the revised cyber bullying inventory (RCBI), the hostility cognition and anger subquestionnaires of the aggression questionnaire (AQ). SPSS 26.0 and SPSS PROCESS macro program were used for descriptive analysis, Pearson correlation analysis and mediating effect test.Results:The prevalence of cyberbullying among college students in the past six months was 20.29%(267/1 316). Dark triad (34.80±12.11), hostile cognition (21.65±7.25), anger (17.58±5.44) and cyberbullying (15.19±3.98) were all significantly positively correlated with each other ( r=0.16-0.59, all P<0.01). The results of mediating effect test showed the indirect effect of dark triad on college students' cyberbullying through two pathways, one was the separate mediating effect of anger, and the effect value was 0.029 (95% CI=0.017-0.044), the other was the chain mediating effect of hostile cognition and anger, and the effect value was 0.037(95% CI=0.023-0.055). Conclusion:Dark triad can not only directly affect college students' cyberbullying, but also indirectly affect cyberbullying through the mediating role of anger and the chain mediating role of hostile cognition and anger.

Early diagnosis value of peripheral blood PPARγ combined with IFN-γ detection for tuberculosis infection in patients with end-stage renal disease / 中国热带医学

@#Abstract: Objective　To explore the early diagnostic value of peripheral blood peroxisome proliferator-activated receptor γ (PPARγ) combined with γ-interferon (IFN-γ) release assay (IGRA) in the diagnosis of pulmonary tuberculosis in patients with end-stage renal disease (ESRD), and to provide reference for clinical diagnosis and treatment. Methods　From January 2019 to December 2021, 70 ESRD patients with suspicious symptoms of pulmonary tuberculosis were treated at Hebei Chest Hospital were selected as the research objects. According to the examination results, they were divided into ESRD group (40 cases) and ESRD complicated by pulmonary tuberculosis (40 cases, comorbidity group). In addition, 40 cases with pulmonary tuberculosis were used as the PTB group. All three groups of patients underwent IGRA test, and the peripheral blood PPARγ level was detected by enzyme-linked immunosorbent assay, and the diagnostic value of PPARγ combined with IGRA test for ESRD patients with pulmonary tuberculosis was explored. Results The expression level of PPARγ and IFN-γ content in the PTB group and the comorbidity group were obviously higher than those in the ESRD group (P<0.05), while the differences in PPARγ expression level and IFN-γ content between the PTB and comorbidity groups were not statistically significant (P>0.05). The ROC curve showed that the areas under the curve (AUC) of PPARγ and IGRA in the diagnosis of end-stage renal disease combined with tuberculosis were 0.823 (95%CI: 0.722-0.925) and 0.773 (95%CI: 0.662-0.883), respectively, and the AUC of combined detection was 0.928 (95%CI: 0.871-0.984), which was better than that of PPARγ and IGRA alone (Z/P=2.057/0.039, 2.843/0.005). The Kappa values of serum PPARγ and IGRA test compared with the clinical gold standard results in the diagnosis of ESRD complicated with pulmonary tuberculosis were 0.557 and 0.444 (P<0.05). The combined screening of ESRD with pulmonary tuberculosis was consistent with the clinical gold standard (Kappa=0.661, P<0.05). Among the 30 ESRD patients complicated with pulmonary tuberculosis, the sensitivity of PPARγ combined with IGRA test in diagnosis of ESRD complicated with pulmonary tuberculosis was 93.33% (28/30), which was higher than 70.00% (21/30) of PPARγ and 66.67% (20/30) of IGRA test alone (P<0.05). Conclusions Peripheral blood PPARγ and IGRA tests have certain diagnostic value for ESRD complicated with tuberculosis, and the combined detection of the two can improve the sensitivity and reduce the rate of missed diagnosis, which is worthy of clinical promotion.

Brucella meningoencephalitis in children with status epilepticus A case report and literature review / 中国热带医学

@#Abstract: Objective　To investigate the clinical characteristics and incidence of Brucella encephalitis and meningitis in children. Methods We report the clinical data of a child with Brucella melitensis meningitis in children, and summarize the incidence, diagnosis methods and treatment of Brucella encephalitis or meningitis in children, taking into account the relevant domestic and foreign literature from January 2014 to December 2020. Results　A 4-year-old girl was admitted to the hospital with status epilepticus on March 15, 2021 because of interrupted right limb numbness for 16 hours and convulsions for 2 hours. She had 2 non-febrile convulsions three months before admission and was diagnosed with epilepsy. This incident was acute, accompanied by low fever, with epilepsy as the main manifestation. Cerebrospinal fluid test suggested central nervous system infection, but the nature of infection could not be determined by routine and biochemistry of cerebrospinal fluid.The cerebrospinal fluid next generation sequencing confirmed that the pathogen of the infection was B. melitensis, which was further verified by the peripheral blood antibody test. After effective antibiotics combined with a full course of treatment, the patient recovered after six months of treatment. A total of 60 articles were retrieved in the database, including 29 in Chinese. During this period, a total of 7 cases of brucellosis in children with nervous system involvement were reported, one of which was a case report, and the other 6 cases were mentioned in the comprehensive analysis of children with brucellosis. Conclusions　Brucella encephalitis or meningitis in children has a low incidence and various clinical features, which are easy to be misdiagnosed or missed.

Two new ursane triterpenoids from Agastache rugosa (Fisch. et.Mey.) O. Kuntze / 药学学报

Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC50 as 4.77, 1.59, 11.11 and 25.87 μmol·L-1, resepectively.

Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure / 国际口腔科学杂志·英文版

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the "m6A site methylation stoichiometry" of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3'-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.

Investigation of medical humanistic practice ability of nurses and factors affecting their practices: a questionnaire-based analysis of 1196 cases in a general hospital in Hunan Province / 南方医科大学学报

OBJECTIVE@#To investigate humanistic practice ability of nurses in a general hospital in Hunan Province and analyze the factors affecting their practices to provide evidence for interventions to improve humanistic practice ability of the nurses.@*METHODS@#A total of 1196 nurses were surveyed using a self-designed questionnaire and a nurse humanistic practice ability assessment scale questionnaire for assessment of their abilities for humanistic care practice, psychological adjustment, interpersonal communication, self-management, ethics and legal practice. Univariate and multivariate analyses were performed for analysis of the factors affecting the practice abilities of the nurses.@*RESULTS@#The total score of humanistic practice ability of the 1196 nurses was 105.69±16.45 (the full score of the scale was 130), and the scores of humanistic care practice ability, psychological adjustment ability, interpersonal communication ability, self-management ability, ethics and legal practice ability were 40.95±6.46, 16.41±2.66, 16.41±2.66, 11.32±2.05 and 12.43±2.00, respectively. Univariate analysis and multiple linear regression analysis showed that gender (P=0.033), age (P < 0.001), department (P=0.015), working years (P < 0.001), professional title (P < 0.001), first academic degree (P < 0.001), highest academic degree (P < 0.001), family location (P=0.010), marital status (P=0.023), number of patients to care for (P=0.022), number of children (P=0.001), previous humanities related training (P < 0.001), training times (P < 0.001), and care received from family members (P < 0.001) and colleagues (P < 0.001) were all the factors affecting humanistic practice ability of the nurses. Among these factors, age, working in department of obstetrics and gynecology and emergency department, professional title, humanities training, and care from family and colleagues explained 20.7% of the variance.@*CONCLUSION@#The humanistic practice ability of nurses in this general hospital is above the average level, but their self-management ability needs to be improved. Intervention measures should be implemented to improve the nurses' humanistic practice ability including more attentions to the key groups and departments, strengthening the training of humanistic practice ability, and improving the promotion assessment system.

Contamination of common food-borne pathogens in foods sold in Changzhou / 公共卫生与预防医学

Objective To understand the contamination status of common food-borne pathogens in foods sold in Changzhou, and to provide evidence for food safety risk assessment and prevention of food-borne diseases. Methods From 2010 to 2020 , 2 513 samples of 17 types of foods were collected in Changzhou area. The detection of pathogenic bacteria was carried out in accordance with the standard operation procedure specified in the “Workbook for Surveillance on Food Microorganisms and Pathogenic Factors in Jiangsu Province”. Results A total of 260 positive samples of common food-borne pathogens were detected in all 2 513 samples with an overall detection rate of 10.30%. Single factor analysis showed that the detection rate of pathogenic bacteria in non-ready-to-eat samples was higher than that in ready-to-eat samples (χ2=148.875，P =0.000). The detection rate of pathogenic bacteria in bulk samples was higher than that in prepackaged ones (χ2=70.956，P=0.000). There is a difference in the detection rate of food-borne pathogens from different types of sampling sites (χ2=65.017，P=0.000). Logistic regression analysis showed that ready-to-eat food, packaging type, and sampling season were significantly correlated with the detection rate of food-borne pathogens. The detection rate of pathogenic bacteria in samples collected in the third or fourth quarters was higher than that in the first quarter. Conclusion The commercial foods sold in Changzhou have a relatively high level of contamination of food-borne pathogenic bacteria, and they should be fully heated and sterilized before consumption. The relevant departments should strengthen supervision and health education in summer and autumn.

Neonatal ureaplasma meningitis: a report of 2 cases and literature review / 中国新生儿科杂志

Objective:To study the clinical features and treatment strategy of neonatal ureaplasma meningitis.Methods:During 2021, the clinical data of 2 neonates with ureaplasma meningitis treated in Children's Hospital of Hunan Province were retrospectively analyzed. Literature on this subject were searched in the following databases: CNKI, Wanfang Database, Chinese Medical Journal Full-Text Database, CQVIP database, SinoMed, PubMed, Embase and Web of Science (up to March 2022). The key words included “infant”, “neonate”, “newborn”, “ureaplasma”, “mycoplasma urealytium”, “meningitis”, “central nervous system infection”, “brain”. The clinical data, treatment and prognosis of patients from the literature were summarized.Results:Case 1, female, gestational age(GA) 33 +3 weeks, intracranial hemorrhage (ICH) and ventricular dilatation were found on 2 d after birth. The cerebrospinal fluid (CSF) routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF metagenomic next-generation sequencing (mNGS) and 23S rRNA showed Ureaplasma urealyticum on 30 d after birth. The patient was treated with doxycycline (DOX) for 21 d until mNGS turned negative and DOX was discontinued. However, the disease recurred 23 d later and erythromycin was added with DOX as combined therapy. The patient was followed up until 6 months without neurodevelopmental disabilities. Case 2, male, GA 26 weeks, ICH and ventricular dilatation were found on 10 d after birth. The CSF routine and biochemistry tests indicated meningitis, but the CSF culture was negative. No improvement after antibiotic treatment. CSF mNGS and 23S rRNA showed Ureaplasma parvum. The patient received erythromycin therapy for 32 d and had normal neurodevelopment at 5 months. According to the literature, 43 cases were reported including the 2 cases descirbed above, 17 cases were full-term infants and 26 cases were preterm infants. The median CSF leukocytes, glucose and proteins were 566 cells/mm 3, 0.2 mmol/L and 2.2 g/L. 27 cases were diagnosed based on CSF culture, 6 cases using mNGS, 4 cases with both CSF culture and PCR method and 6 cases with other methods. Macrolides alone were used in 14 cases, macrolides combined with another antibiotic were used in 8 cases, non-macrolide antibiotics were used in 9 cases and 12 cases didn't receive any anti-ureaplasma therapy. All 17 term infants survived, however, 8 cases with hydrocephalus. Among the 26 preterm infants, 8 patients died, 18 patients had periventricular-intraventricular hemorrhage and 15 patients had hydrocephalus. Conclusions:Neonatal ureaplasma meningitis has significantly lower CSF glucose level with hydrocephalus as the common complication. For intracranial infections of unknown etiology and no response to treatment, mNGS is helpful in determining the pathogen.Neonatal ureaplasma meningitis should be treated with macrolides alone or as add-on therapy.

Research on BHLHE40 targets HMGA2 to reduce the sensitivity of thyroid cancer cells to cisplatin through activating the oxidative phosphorylation pathway / 国际肿瘤学杂志

Objective:To explore whether BHLHE40 can affect the sensitivity of thyroid cancer (TC) cells to cisplatin by activating oxidative phosphorylation (OXPHOS) pathway by targeting high mobility group A2 (HMGA2) .Methods:The mRNA expression of HMGA2 and its upstream transcription factor BHLHE40 in TC tissues was analyzed by TCGA-THCA and hTFtarget online databases. The si-HMGA2, oe-HMGA2, oe-BHLHE40, negative control si-NC and oe-NC were transfected into TC cells (K1 and SW579) by liposome transfection method. The mRNA expression levels of BHLHE40 and HMGA2 in TC cells (SW579, FTC-133, and K1) and normal thyroid cells (Nthy ori3-1) were detected by real-time quantitative PCR (qRT-PCR). The cell viability was detected by MTT assay, the half inhibitory concentration (IC 50) value of cisplatin was calculated by CCK-8 assay, the apoptosis level was detected by flow cytometry, and the expression of OXPHOS complex was detected by Western blotting. Seahorse XFe 96 was used to analyze the oxygen consumption rate of the TC cells. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay were used to analyze the binding relationship between BHLHE40 and HMGA2. Results:TCGA database results showed that the mRNA expression levels of HMGA2 and BHLHE40 in TC tissues (10.57±2.58, 13.89±1.13) were higher than those in normal thyroid tissues (4.82±1.69, 12.28±1.01), with statistically significant differences ( t=16.69, P<0.001; t=10.43, P<0.001). The results of qRT-PCR showed that the relative mRNA expression levels of HMGA2 in normal thyroid cells (Nthy ori3-1) and TC cells (SW579, FTC-133, and K1) were 1.00±0.13, 2.94±0.23, 4.71±0.41 and 6.29±0.49, while those of BHLHE40 were 1.00±0.12, 2.60±0.23, 3.39±0.35 and 6.18±0.51 respectively, both with statistically significant differences ( F=130.50, P<0.001; F=125.20, P<0.001). Further pairwise comparison showed that mRNA expression levels of HMGA2 and BHLHE40 in TC cells were significantly higher than those in normal thyroid cells (all P<0.001). According to MTT experimental results, si-HMGA2 treatment significantly reduced the cell viability of K1 cells compared to the si-NC group (all P<0.05). In addition, compared to the oe-NC group, oe-HMGA2 treatment significantly increased the cell viability of SW579 cells (all P<0.05). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed enhanced cell viability of SW579 cells, while the OXPHOS pathway inhibitor Gboxin was able to reverse the effect of overexpressing HMGA2 on cell viability (all P<0.05). The results of flow cytometry and CCK-8 experiments showed that compared to the si-NC group (apoptosis level: 6.19%±0.28%; cisplatin IC 50 value: 17.47 μmol/L), knocking down HMGA2 could increase the apoptosis level (11.96%±0.32%; t=19.17, P<0.001) and cisplatin sensitivity (IC 50 value: 1.49 μmol/L) of K1 cells. In addition, compared to the oe-NC group (apoptosis level: 9.98%±0.32%; cisplatin IC 50 value: 8.17 μmol/L), overexpressing HMGA2 significantly decreased the apoptosis level (4.32%±0.25%; t=19.65, P<0.001) and cisplatin sensitivity (IC 50 value: 34.95 μmol/L) of SW579 cells. The results of dual-luciferase assay showed that compared with the si-NC group, knocking down the expression of BHLHE40 in human kidney epithelial 293T cells significantly reduced the luciferase activity of wild-type HMGA2 (0.31±0.02 vs. 1.00±0.11; t=10.69, P=0.004). However, there was no significant effect on the luciferase activity of mutant-type HMGA2 (1.06±0.11 vs. 1.00±0.07; t=0.80, P=0.470). ChIP results showed that the mRNA expression level of HMGA2 in K1 cells was significantly increased in the anti-BHLHE40 group (6.57±0.62) compared with the IgG group (1.00±0.10; t=15.36, P<0.001). Compared to the oe-NC+DMSO group, the oe-HMGA2+DMSO group showed decreased apoptosis level ( P<0.05) and cisplatin sensitivity of SW579 cells, with a significant increase in the expression of OXPHOS complexes Ⅰ-Ⅴ and cellular oxygen consumption rates (all P<0.05). The effect of overexpressing HMGA2 was reversed by treatment with oe-HMGA2+Gboxin (all P<0.05). The recovery experiment showed that compared to the oe-NC+si-NC group, overexpression of BHLHE40 in SW579 cells increased cell viability and the expression of OXPHOS complexes Ⅰ-Ⅴ, while decreasing apoptosis levels and increasing cellular oxygen consumption rates and cisplatin IC 50 values (all P<0.05). However, simultaneous knockdown of HMGA2 reversed the effect of overexpressing BHLHE40 (all P<0.05) . Conclusion:BHLHE40 can activate the OXPHOS pathway by targeting and regulating the expression of HMGA2, thereby affecting the sensitivity of TC cells to cisplatin.

Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance / 国际肿瘤学杂志

Objective:To analyze the expression of targeting protein for Xklp2 (TPX2) in kidney renal clear cell carcinoma (KIRC) and its clinical significance.Methods:The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology, the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database, which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage, molecular subtypes, lymph node metastasis, and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins, and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database.Results:Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% (26/54) in cancer tissues, which was higher than that in paracancerous tissues (20.37%, 11/54) ( χ2=9.25, P=0.002). The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 (1.49, 2.42), normal tissue: 0.35 (0.24, 0.57), U=2 297.00, P<0.001]. The expression of TPX2 mRNA was related to the clinical stage ( χ2=34.36, P<0.001), molecular subtypes ( χ2=30.15, P<0.001), and lymph node metastasis status ( χ2=27.21, P<0.001) of KIRC patients. The 5-year survival rate (53.80%) in patients with high TPX2 expression was lower than that in patients with low TPX2 expression (74.40%, χ2=18.87, P<0.001). STRING database protein interaction network construction obtained 20 TPX2-related proteins, and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells ( r=0.30, P<0.001), CD8 + T cells ( r=0.23, P<0.001), CD4 + T cells ( r=0.18, P<0.001), macrophages ( r=0.20, P<0.001), neutrophils ( r=0.31, P<0.001), dendritic cells ( r=0.39, P<0.001) infiltration and most of its biomarkers (all P<0.05). It was positively correlated with immune checkpoint PD-1 ( r=0.31, P<0.001) and CTLA-4 ( r=0.27, P<0.001), but not correlated with PD-L1 ( r=0.07, P=0.146) . Conclusion:TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.

Comparison of safety and efficacy of 7.5 Fr and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm / 国际外科学杂志

Objective:To compare the safety and efficacy of 7.5 Fr and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm.Methods:Using a prospective randomized controlled study method, 96 patients with upper urinary tract calculi with maximum diameter<1.5 cm admitted to the Department of Urology, Beijing Friendship Hospital, Capital Medical University from August 2020 to May 2022 were selected as the study subjects. The patients were divided into two groups by random number table method: the experimental group and the control group, with 48 patients in each group. The experimental group patients underwent 7.5 Fr flexible ureteroscopic lithotripsy, while the control group patients underwent 9.5 Fr flexible ureteroscopic lithotripsy. Collect preoperative, intraoperative, and postoperative data from these patients, including success rate of ureteral access sheath insertion, surgical time, lithotripsy time, stone-free rate, ureteral injury status, and complications status. The measurement data were expressed as mean±standard deviation ( ± s), Student- t test was used for comparison between groups; the Chi-square test was used for inter-group comparison of count data, and the Mann-Whitney U test was used for inter-group comparison of rank data. Results:The success rate of primary sheath insertion in the experimental group was 93.8% (45/48), and that in the control group was 79.2% (38/48), the difference between the two groups was statistically significant ( P<0.05). There were no statistically significant difference between the experimental group and the control group in terms of surgical time [(52.0±11.0) min vs (55.1±11.4) min, P>0.05] and lithotripsy time [(26.0±9.3) min vs (23.7±8.7) min, P>0.05]. At four weeks after surgery, the stone-free rate in the experimental group was 93.3% (42/45), while that in the control group was 97.4% (37/38), there was no statistically significant difference between the two groups ( P>0.05). In terms of the degree of ureteral injury, there were 17 patients had grade 0 injury, 27 patients had grade 1 injury, 4 patients had grade 2 injury, and no patient had grade 3 injury in the experimental group; there were 9 patients had grade 0 injury, 23 patients had grade 1 injury, 13 patients had grade 2 injury, and 3 patients had grade 3 injury in the control group; the difference between the two groups was statistically significant ( P<0.05). In terms of complications, there were 22 cases of hematuria, 9 cases of pain, 8 cases of bladder spasm, and 2 cases of mild fever in the experimental group; there were 24 cases of hematuria, 12 cases of pain, 9 cases of bladder spasm, and 1 case of mild fever in the control group; there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The application of 7.5 Fr flexible ureteroscopy and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm can achieve good stone-free rates, but the 7.5 Fr flexible ureteroscopy has a higher success rate of sheath insertion and less damage to the ureter.

Expression and Significance of Lactate Dehydrogenase A in Renal Cell Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo analyze the expression of Lactate dehydrogenase A（LDHA） in both renal cell carcinoma （RCC） tissue and RCC cell lines， and to investigate the impact of LDHA expression on the progression of RCC. MethodsFrom June 2018 to June 2022， totally 52 cases of RCC tissue samples and 49 cases of para-cancerous tissue samples were collected through surgical procedures from our hospital. LDHA expression was detected using immunohistochemistry （IHC）. The expression levels of LDHA in vitro were also detected in the normal human proximal tubule epithelial cell line HK-2 and renal cell carcinoma cell lines A498， Caki-2， ACHN， and 786-O by using qRT-PCR and Western blot. A recombinant plasmid carrying LDHA-shRNA was constructed and then transfected into 786-O cells to down-regulate the expression of LDHA. Tumor proliferative capacity was monitored using CCK-8 assay， clonal formation assay and EdU assessments. Additionally， cell glycolytic activity was assessed through glucose uptake assay， lactate secretion assay， and ECAR analysis. ResultsIHC analysis revealed significantly higher expression of LDHA in RCC tissue compared to adjacent tissues（P<0.05）. Furthermore， RCC tissues with higher TNM stage exhibited greater expression of LDHA than those with lower TNM stage （P<0.05）. The results of qRT-PCR and Western blot demonstrated that the expression of LDHA in each RCC cell line was significantly higher than that in HK-2（P<0.05）. After blocking the expression of LDHA in 786-O， there was a significant down-regulation of cell proliferation and glycolysis capacity （P<0.05）. ConclusionsThe expression of LDHA in RCC tissue and RCC cell lines is significantly overexpressed compared with normal one， particularly in those with higher TNM stage. Knockdown of the expression of LDHA significantly suppresses cell proliferation and aerobic glycolysis capacity in 786-O.

Comparison of safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by flexible ure-teroscopy / 北京大学学报(医学版)

OBJECTIVE@#To compare the safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by retrograde flexible ureteroscopy.@*METHODS@#A total of 90 patients with 1-2 cm upper ureteral calculi treated in the urology department of Beijing Friendship Hospital from August 2018 to August 2020 were selected as the subjects. The patients were divided into two groups using random number table: 45 patients in group A were treated with in situ lithotripsy and 45 patients in group B were treated with active migration technique. The active migration technique was to reposition the stones in the renal calyces convenient for lithotripsy with the help of body position change, water flow scouring, laser impact or basket displacement, and then conduct laser lithotripsy and stone extraction. The data of the patients before and after operation were collected and statistically analyzed.@*RESULTS@#The age of the patients in group A was (51.6±14.1) years, including 34 males and 11 females. The stone diameter was (1.48±0.24) cm, and the stone density was (897.8±175.9) Hu. The stones were located on the left in 26 cases and on the right in 19 cases. There were 8 cases with no hydronephrosis, 20 cases with grade Ⅰ hydronephrosis, 11 cases with grade Ⅱ hydronephrosis, and 6 cases with grade Ⅲ hydronephrosis. The age of the patients in group B was (51.8±13.7) years, including 30 males and 15 females. The stone diameter was (1.52±0.22) cm, and the stone density was (964.6±214.2) Hu. The stones were located on the left in 22 cases and on the right in 23 cases. There were 10 cases with no hydronephrosis, 23 cases with grade Ⅰ hydronephrosis, 8 cases with grade Ⅱ hydronephrosis, and 4 cases with grade Ⅲ hydronephrosis. There was no significant diffe-rence in general parameters and stone indexes between the two groups. The operation time of group A was (67.1±16.9) min and the lithotripsy time was (38.0±13.2) min. The operation time of group B was (72.2±14.8) min and the lithotripsy time was (40.6±12.6) min. There was no significant difference between the two groups. Four weeks after operation, the stone-free rate in group A was 86.7%, and in group B was 97.8%. There was no significant difference between the two groups. In terms of complications, 25 cases of hematuria, 16 cases of pain, 10 cases of bladder spasm and 4 cases of mild fever occurred in group A. There were 22 cases of hematuria, 13 cases of pain, 12 cases of bladder spasm and 2 cases of mild fever in group B. There was no significant difference between the two groups.@*CONCLUSION@#Active migration technique is safe and effective in the treatment of 1-2 cm upper ureteral calculi.

Progress in evaluating the risk of lymph node metastasis in early colorectal cancer / 中华胃肠外科杂志

Early colorectal cancers refer to invasive cancers that have infiltrated into the submucosa without invading muscularis propria, and approximately 10% of these patients have lymph node metastases that cannot be detected by conventional imaging. According to the guidelines of Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer, early colorectal cancer cases with risk factors for lymph node metastasis (poor tumor differentiation, lymphovascular invasion, deep submucosal invasion and high-grade tumor budding) should receive salvage radical surgical resection; however, the specificity of this risk-stratification is inadequate, making most patients undergo unnecessary surgery. Firstly, this review focuses on the definition, oncological impact importance and controversy of the above "risk factors". Then, we introduce the progress of the risk stratification system for lymph node metastasis in early colorectal cancer, including the identification of new pathological risk factors, the construction of new risk quantitative models based on pathological risk factors, artificial intelligence and machine learning technology and the discovery of novel molecular markers associated with lymph node metastasis based on gene test or liquid biopsy. Aim to enhance clinicians' understanding of the risk assessment of lymph node metastasis in early colorectal cancer; we suggest to take the patient's personal situation, tumor location, anti-cancer intention and other factors into account to make individualized treatment strategies.