Objective To investigate the mechanism of apoptosis induced by acetyl-11-keto-3-boswellic acid(AKBA)in oral squamous cell carcinoma(OSCC)cells.Methods CAL27 were randomly divided into control group(conventional culture),low-dose group(40.00 μmol·L-1 AKBA),middle-dose group(80.00 μmol·L-1 AKBA),high-dose group(120.00 μmol·L-1 AKBA),3-methyladenine(3-MA)group(120.00 μmol·L-1 AKBA+2 mmol·L-1 autophagy inhibitor 3-MA).5-ethynyl-2'-deoxyuridine(Edu)assay was used to detect cell proliferation;Western blot assay was used to detect protein expression;flow cytometry was used to detect apoptosis.Mice were randomly divided into model group(construct OSCC mouse model),AKBA-L group(10.00 mg·kg-1 AKBA after modeling),AKBA-H group(20.00 mg·kg-1 AKBA after modeling),10 animals per group.After 28 days of continuous administration,weight were detected;and the expression of related proteins were detected by Western blot assay.Results The Edu positive cell rates in control group,high-dose group were(40.18±2.53)％,(12.08±0.93)％,respectively;the protein levels of autophagy associated microtubule associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ in control group,high-dose group and 3-MA group were 0.33±0.05,2.93±0.39,0.56±0.07,respectively;phosphorylated adenylate activated protein kinase catalytic subunit alpha subunit 1(p-PRKAA1)protein levels were 0.34±0.04,1.03±0.07,0.99±0.09,respectively;the apoptosis rates were(4.65±0.39)％,(25.75±2.29)％,(14.92±1.49)％,respectively.The above indexes in hige-dose group were significantly different from those in the control group(all P＜0.05).The above indexes in 3-MA group were significantly different from those in high-dose group(all P＜0.05).The tumor weight of model group,AKBA-L group and AKBA-H group were(0.96±0.08),(0.55±0.06),(0.43±0.05)g,respectively;the protein levels of LC3 Ⅱ/LC3 Ⅰ were 0.47±0.09,0.94±0.21 and 1.69±0.34,respectively.The above indexes in AKBA-L group and AKBA-H group were significantly different from those in model group(all P＜0.05).Conclusion AKBA can induce cytotoxic autophagy related apoptosis and inhibit CAL27 cell proliferation,which may be related to activation of AMPK signal.

Cervical spondylotic radiculopathy(CSR)is a condition caused by the degeneration of cervical intervertebral discs and facet joints,primarily manifesting as the pain,sensory abnormalities,and motor dysfunction in the cervical nerve innervation area of neck,shoulder,and upper limb.For the treatment of CSR,tendon-bone syndrome differentiation in traditional Chinese medicine often faces the issues of conceptual confusion and non-standard syndrome differentiation.Based on the traditional tendon-bone syndrome differentiation and by integrating modern anatomical insights,Professor LIN Ding-Kun,an esteemed scholar of Traditional Chinese Medicine,proposed a classification system for the cervical spine that includes the categories of tendons,joints,bones and marrow.This paper explored the thoughts of Professor LIN for the tendon-bone syndrome differentiation of CSR,summarized the targets of manual therapy,and proposed the four kinds of pathological changes such as tendon overstrain,joint dislocation,bone lesion,and marrow injury,as well as the four techniques of traditional Chinese medicine manipulations,i.e.relaxation of tendons,reduction of joints,protection of marrow,and treatment of bones.The aim is to improve the syndrome-differentiation and treatment for CSR with orthopedic and traumatologic manipulations,and to provide reference for clinical practice.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective:To compare the efficacy of amide proton transfer-weighted (APTw) imaging with time-dependent diffusion MRI (td-dMRI) in the diagnosis of malignant breast lesions.Methods:This study was a cross-sectional study. The clinical, pathological and imaging data of patients with breast lesions admitted to the First Affiliated Hospital of Zhengzhou University from March to August 2023 were prospectively analyzed. All patients firstly underwent T 2WI, diffusion-weighted imaging, followed by dynamic contrast-enhanced MRI (DCE-MRI), and finally APTw imaging and td-dMRI were performed for breast lesions using DCE-MRI as reference. Reconstructed images from APTw imaging measured lesions with a frequency shift of 3.5 ppm asymmetric magnetic susceptibility MTR asym(+3.5 ppm). The apparent diffusion coefficient (ADC) values at different oscillating frequency gradients (ADC PGSE, ADC 17 Hz, ADC 33 Hz values) were measured using reconstructed td-dMRI images. Independent sample t-test was used to compare APTw imaging, td-dMRI parameter differences between benign and malignant breast tumors, breast malignant tumors with different molecular types [estrogen receptor (ER) negative and positive, progesterone receptor (PR) negative and positive, human epidermal growth factor receptor (HER-2) negative and positive, proliferation index (Ki-67) low and high expression] and different histological grades (grade Ⅱ and Ⅲ). Receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the efficacy of APTw imaging and td-dMRI parameters in differentiating benign and malignant breast tumors, molecular classification and histological grading of malignant breast lesions. Results:There were 171 lesions in 171 patients, including 103 malignant lesions and 68 benign lesions. Histological grades were grade Ⅱ in 51 cases and grade Ⅲ in 38 cases of 89 cases of invasive carcinoma. Totally 98 cases of malignant lesions were included in molecular typing analysis, 36 cases were ER negative and 62 cases were ER positive. PR was negative in 51 cases and positive in 47 cases. There were 33 negative HER-2 patients, 65 positive HER-2 patients. There were 50 cases of low Ki-67 expression and 48 cases of high Ki-67 expression. The MTR asym(+3.5 ppm) value of malignant breast lesions was higher than that of benign lesions ( t=5.76, P<0.001), and the ADC PGSE, ADC 17 Hz and ADC 33 Hz values were lower than those of benign breast lesions ( t was 4.84, 4.62, 4.01, respectively, all P<0.001). MTR asym(+3.5 ppm) had the highest AUC value (0.83) and the highest specificity (90.38%), and ADC PGSE had the highest sensitivity (85.86%). There were no significant differences in MTR asym(+3.5 ppm), ADC PGSE, ADC 17 Hz and ADC 33 Hz between grade Ⅱ and grade Ⅲ histological grades of malignant breast lesions (all P>0.05). The ADC PGSE value of ER negative was higher than that of ER positive ( t=2.34, P=0.018), and the AUC for distinguishing ER positive from negative was 0.64. The ADC PGSE and ADC 17 Hz values of PR negative were higher than those of PR positive ( t=2.87, 2.81, P=0.004, 0.006, respectively), and their AUCs for identifying PR positive versus negative breast malignant lesions were 0.68 and 0.67, respectively. The ADC 33 Hz value of negative HER-2 was lower than that of positive HER-2 ( t=3.00, P=0.003), and the AUC for distinguishing positive and negative HER-2 was 0.67. There were no significant differences in other parameters among different subtypes of breast malignant lesions (all P>0.05). Conclusion:Compared with td-dMRI, APTw imaging is more effective in differentiating benign and malignant lesions of breast tumors, and ADC values at different gradient oscillation frequencies obtained by td-dMRI show better diagnostic efficacy in differentiating different molecular types of breast malignant lesions.

Objective: To establish and validate a nomogram model for predicting the risk of microvascular invasion(MVI) in hepatocellular carcinoma. Methods: The clinical data of 210 patients with hepatocellular carcinoma who underwent hepatectomy at Department of Hepatobiliary and Pancreatic Surgery,the Affiliated Hospital of Qingdao University from January 2013 to October 2021 were retrospectively analyzed. There were 169 males and 41 females, aged(M(IQR)) 57(12)years(range:30 to 80 years). The patients were divided into model group(the first 170 cases) and validation group(the last 40 cases) according to visit time. Based on the clinical data of the model group,rank-sum test and multivariate Logistic regression analysis were used to screen out the independent related factors of MVI. R software was used to establish a nomogram model to predict the preoperative MVI risk of hepatocellular carcinoma,and the validation group data were used for external validation. Results: Based on the modeling group data,the receiver operating characteristic curve was used to determine that cut-off value of DeRitis ratio,γ-glutamyltransferase(GGT) concentration,the inverse number of activated peripheral blood T cell ratio (-aPBTLR) and the maximum tumor diameter for predicting MVI, which was 0.95((area under curve, AUC)=0.634, 95%CI: 0.549 to 0.719), 38.2 U/L(AUC=0.604, 95%CI: 0.518 to 0.689),-6.05%(AUC=0.660, 95%CI: 0.578 to 0.742),4 cm(AUC=0.618, 95%CI: 0.533 to 0.703), respectively. Univariate and multivariate Logistic regression analysis showed that DeRitis≥0.95,GGT concentration ≥38.2 U/L,-aPBTLR>-6.05% and the maximum tumor diameter ≥4 cm were independent related factors for MVI in hepatocellular carcinoma patients(all P<0.05). The nomogram prediction model based on the above four factors established by R software has good prediction efficiency. The C-index was 0.758 and 0.751 in the model group and the validation group,respectively. Decision curve analysis and clinical impact curve showed that the nomogram model had good clinical benefits. Conclusions: DeRitis ratio,serum GGT concentration,-aPBTLR and the maximum tumor diameter are valuable factors for preoperative prediction of hepatocellular carcinoma with MVI. A relatively reliable nomogram prediction model could be established on them.
Female ; Humans ; Male ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Neoplasm Invasiveness ; Nomograms ; Retrospective Studies ; Risk Factors ; Adult ; Middle Aged ; Aged ; Aged, 80 and over

ObjectiveTo compare the nocturnal erectile function between SRPE patients and normal people. MethodsFrom July 1st， 2019 to December 15th， 2022， a clinical comparative study was conducted on 29 SRPE patients （experimental group） and 58 volunteers （control group） who visited our urology department. The Rigiscan System was used to monitor sleep monitoring time， the number of nocturnal erections and the rigidity， duration and circumference growth of the penis when the erection reached 60%～79% and 80%～100%， respectively. The patients and volunteers were asked to make written records when they woke up， and then the total number of awakenings and the number of awakenings when the penis erection reached 60% and 80% were compared between the two groups. ResultsAge was eliminated by matching. There was no statistically significant difference in sleep monitoring time， rigidity， circumference growth and duration of the penis when the erection reached 60%～79% and 80%～100%. between the two groups. In terms of sleep， there was a statistically significant difference in the total number of awakenings between the two groups［3（2 ~ 4）vs 0（0 ~ 0），P<0.01］ .And the same was true for the number of awakenings when the penis erection exceeded 60%～79% ［1（0 ~ 1）vs 0（0 ~ 0），P<0.01］and 80%～100% ［2（1 ~ 3）vs 0（0 ~ 0），P<0.01］. ConclusionRigiscan monitoring showed that there was no difference between SRPE patients and normal male in nocturnal penile erection function. Painful awakening usually occurs when the penis erection reaches 60%～79% or 80%～100%， which reveals that SRPE may be caused by abnormal sensation of nocturnal erections or pain sensitivity in some of these patients.

Abstract: Objective To investigate the epidemiological characteristics of pathogens causing bloodstream infection in hematology patients during treatment and to compare the effects of allogeneic hematopoietic stem cell transplantation (HSCT) on them, so as to provide evidence for the diagnosis and treatment of bloodstream infection. Methods A total of 292 cases with bloodstream infection in hematology wards of the PLA General Hospital were collected from 2017 to 2021, which were divided into HSCT group and N-HSCT group according to whether performed HSCT or not. The epidemiological characteristics and influence of pathogenic bacteria in blood stream infection were analyzed and compared between the two groups. Results A total of 362 strains of pathogenic bacteria were collected from 292 cases, including 106 strains in HSCT group (84 cases) and 256 strains in N-HSCT group (208 cases). Bloodstream infections were more common in acute myeloid leukemia (130/392, 44.52%), followed by non-Hodgkin's lymphoma (74/292, 25.34%). The rate of once bloodstream infection in HSCT group was higher than that in N-HSCT Group, but the rate of twice bloodstream infections in N-HSCT group was higher. Gram-negative Bacilli were the most common pathogens (56.08%), with Escherichia coli being absolutely dominant (109/362, 30.11%), followed by Klebsiella pneumoniae (39/362, 10.77%). Coagulase-negative staphylococci (CoNS) (107/362, 29.56%) were the most common Gram-positive cocci. The detection rate of fungi in HSCT group (10/106, 9.43%) was significantly higher than that in N-HSCT Group (3.52%). The drug resistance rate of the common pathogenic bacteria was at a high level, and there was a certain proportion of multi-drug resistant strains (except for Pseudomonas aeruginosa). The resistance rates of CoNS to penicillin, gentamicin, moxifloxacin, clindamycin and rifampicin in HSCT group were higher than those in N-HSCT Group. The resistance rate of Escherichia coli to piperacillin/tazobactam, cephalosporins and etapenem in HSCT group was significantly higher than that in N-HSCT group. Conclusions The pathogens of blood stream infection in hematology patients are complicated and various. It is difficult for clinical diagnosis and treatment to detect multiple infections and multiple pathogens. HSCT patients have a higher risk of fungal bloodstream infection and more multi-drug resistant strains detected. Therefore, the identification of bloodstream infection and multi-drug resistant strains associated with HSCT patients should prompt surveillance.

Humans ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation, Missense ; Proline Oxidase/genetics*

Aim To study the mechanism of the ethanol extract from Leucopaxillus giganteus (LGEE) in treating breast cancer based on network pharmacology and molecular experimental validation. Methods Some chromatographic methods were used to isolate the chemical constituents of LGEE, and their structures were elucidated based on spectral data. The antitumor activities of LGEE were determined by MTT assay. The predicted targets of LGEE were selected by TCMSP and Pharmmaper, and Genecards database was used to screen the targets. GO and KEGG analysis of target genes were performed. Molecular docking was used to test the binding of active components to core targets. Western blotting was used to validate the regulating function of chlorogenic acid on CHEK2 and CASP3 targets of MDA-MB-231 cells. Results Thirteen compounds were identified including clitocine, chlorogenic acid and so on. LGEE displayed anticancer activities against MDA-MB-231 with the inhibition percent (87. 35 ± 1. 55)%, at the concentration of 200 mg· L

【Objective】 To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test. 【Methods】 An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified. SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection, two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results, and pseudovirus neutralization experiments with different virus strain (prototype strain, BA. 1,BA.2, BA.4/5, BF.7, BQ.1.1) were carried out to determine the distribution of neutralizing antibodies against different virus strain. SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected, including Omicron convalescent plasma (OP) collected from different plasma stations from December 2022 to May 2023 and normal pool plasma (VN) feed in March 2023 which collected from March 2022 to December 2022. According to the results, the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed. 【Results】 The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL, the accuracy in-batch ranged from 81.793% to 106.985%, the precision in-batch ranged from 1. 100% to 13.000%, and the total error in-batch ranged from 2.988% to 22.679%. The accuracy between batches ranged from 90.788%to 96.893%, the precision between batches ranged from 4.870% to 6.272%, and the total error between batches ranged from 9.192% to 15.399%. The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype strain>BA.2>BA.4/5>BF.7≈ BQ.1.1>BA.1 and the correlation between WP1 and WP2 was high (Pearson r=0. 931 1, P=0.002 3) which indicated that the potency distribution of neutralizing antibodies of different virus strain in Omicron convalescent plasma was basically stable. Compared with the mixed convalescent plasma sample G128 collected in June 2022, the potency of Omicron neutralizing antibodies of WP series were significantly higher, the ratio of BA.2 antibody to prototype antibody increased from 26.9% (before infection) to 82.6%-87.5% (after infection). The results of VN series before Omicron infection were < 100 EIU/mL, and the results of OP series after Omicron infection showed that the plasma collected from the beginning of December 2022 was the peak of antibody in the same month,and then dropped sharply, entering a short plateau in February-March 2023 (potency was about 40% of the peak value),and then dropped sharply again in April (potency was about 20% of the peak value). 【Conclusion】 The potency and proportion of neutralizing antibody against Omicron subtype in convalescent plasma after COVID-19 Omicron strain infection increased significantly. IgG antibody of plasma donors in different regions reached its peak in the month of infection, then continued to dropped sharply. The best collection period of plasma that can be used for human COVID-19 immunoglobulin for intravenous injection was 1 to 2 months after infection.