Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Objective To develop a method for the determination of ketamine analogues in hair samples by liquid chromatography quadrupole linear ion trap mass spectrometry(QTRAP LC-MS/MS).Methods 20 mg of washed and dried hair was added to 1 mL extracting solution and then prepared using an ultrasonic extraction with frozen pulverization method.After centrifugation and purification with membrane,the supernatant was separated in a ACQUITY UPLC? HSS T3 column with gradient elution,finally tested with multiple reaction monitoring for the detection of 10 ketamine analogues.The above method was applied for quantitative analysis of ethylfluamine,F-norketamine and tiletamine in 20 positive samples.Results When the concentration ranged from 0.01 to 2.00 ng/mg,there was good linearity for 10 ketamine analogues with the correlation coefficients over 0.99.The recoveries ranged from 89.1％to 106.1％,and the matrix effects were between 88.3％and 106.0％.Among the 20 positive samples,the contents of ethylfluamine,F-norketamine and tiletamine in hair ranged between 0.02～8.35 ng/mg,0.01～0.94 ng/mg and 0.02～10.93 ng/mg,respectively.Their mean values were 1.59 ng/mg,0.28 ng/mg and 2.69 ng/mg.Their medians were 0.40 ng/mg,0.19 ng/mg and 2.11 ng/mg.Conclusion The established method was simple,efficient,reliable and suitable for the determination of ketamine analogues in hair.The data provided reference for the drug control and forensic science practice.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Objective To investigate the clinical effect of digital subtraction angiography(DSA)-guided foam sclerotherapy on lower limb varicose veins.Methods The relevant data of patients with lower limb varicose veins treated by DSA-guided foam sclerotherapy were analyzed retrospectively.At the same time,the safety and efficacy were compared before and after operation according to clinical etiology anatomy pathophysiology(CEAP)and clinical symptoms.Results Among the 278 affected limbs treated,2(0.72％)had neurological complications during treatment,8(2.88％)had chest tightness or cough during treatment,7(2.52％)had thrombophlebitis after treatment,and 28(10.07％)had hyperpigmentation after treatment.No serious complications such as skin necrosis,deep vein thrombosis(DVT)or pulmonary embolism(PE)occurred.There were 48 cases of grade C1 and 201 cases of grade C2 before treat-ment,while 244 cases of grade C0 and 26 cases of grade C1 after treatment,and the differences were statistically significant(P＜0.05).Conclusion DSA-guided foam sclerotherapy on lower limb varicose veins is a safe and effective minimally invasive treatment with high technical success rate.

BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION Chictr.org, ChiCTR 1800018895.
Humans ; Aged ; Sarcopenia/diagnosis* ; Deep Learning ; Aging ; Algorithms ; Biomarkers

Circular RNAs(circRNAs)are involved in various biological processes and disease pathogenesis.However,only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species,partly because most current methods are based on cir-cular junction counts and overlook the fact that a circRNA is formed from the host gene by back-splicing(BS).To distinguish the expression difference originating from BS or the host gene,we pre-sent differentially expressed back-splicing(DEBKS),a software program to streamline the discov-ery of differential BS events between two rRNA-depleted RNA sequencing(RNA-seq)sample groups.By applying to real and simulated data and employing RT-qPCR for validation,we demon-strate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups.

【Objective】 To establish and evaluate a nephelometric assay for the determination of immunoglobulin A (IgA) residues in human intravenous immunoglobulin(IVIG). 【Methods】 BN ProSpec^© automatic protein analyzer and its supporting immunoglobulin A determination kit (nephelometry) produced by German Siemens and the national standard of human IgA were used to establish the nephelometric assay to determine IgA residue in test products and verify the methodology. The test products include IVIG (pH4) prepared by low-temperature ethanol protein separation process and a novel IVIG prepared by chromatography. 【Results】 The average deviation of three calibration curves for IgA residues determination by the nephelometric assay were 1.08%, 0.95% and 1.54%,, and the three deviations of the quality control were 4.00%, -2.30% and -0.20%, respectively, which indicated good calibration and quality control. In the specificity test, the average recovery rates of IgA for reference substance 1 containing 100g/L maltose and reference substance 2 containing 20g/L glycine were 102.7% and 105.8%, respectively. The relative standard deviation (RSD) values of the repeatability tests of the two test products were 3.9% and 1.9%, and the RSD values of the intermediate precision test were 3.6% and 2.3%, respectively.The difference values at each time point in the durability test of test products′ storage time were all less than 10%, and the RSD values of the two test products in the durability test of kits of different batches were 2.8% and 2.2%, respectively. In the accuracy test, the average recovery rates of IVIG (pH4) added to the standard were 94.2%, 101.7% and 96.2%, respectively, and the average recovery rates of the novel IVIG added to the standard were 102.8%, 106.3% and 99.7%, respectively. The average recovery rate of the limit quantification test was 101.0%, and the RSD was 4.0%. 【Conclusion】 Nephelometric assay has the advantages of strong specificity, high precision and accuracy, good repeatability, simple and rapid operation, and automation, and can be used for the determination of IgA residue in IVIG (pH4) and novel IVIG products.

Objective To establish a risk warning model for surgical site infection(SSI), provide support for screening high risk population and finding suspected cases.Methods Clinical data of 5 067 patients who underwent abdominal surgery in 6 domestic hospitals from January 2013 to December 2015 were collected retrospectively, all cases were randomly divided into modeling group and validation group according to a 6:4 ratio, warning model was established by employing logistic regression, the area under the receiver operating characteristic curve (AUC) was used to evaluate discriminant ability of evaluation model, the maximum Youden index was as the optimum cut-off point.Results For the warning model of high-risk patients, AUC was 0.823, sensitivity and specificity were 78.81% and 74.33% respectively, positive predictive value and negative predictive value were 19.67% and 97.78% respectively.For the discriminant model of suspected infection cases, AUC was 0.978, sensitivity and specificity were 93.38% and 95.62% respectively, positive predictive value and negative predictive value were 62.95% and 99.45% respectively.Conclusion The early-warning model established in this study has better discrimination ability, which can provide a reference for the development of early warning and discrimination of healthcare-associated infection information system.

Objective To understand the status of awareness of hand hygiene(HH)knowledge and compliance among health care workers (HCWs)in China,and provide scientific basis for further improvement of HH practice. Methods A multi-centre retrospective survey on awareness of HH knowledge and compliance was conducted in 200 nationwide hospitals in 2015.Results The awareness rates of HH methods and HH indications among HCWs were 86.5% and 82.5% respectively;cleaning staff had the lowest awareness rate of HH indications(69.9%),followed by the other interns and advanced-study students (70.2%),as well as medical technicians (79.8%);attendants had the lowest awareness rate of HH methods(76.9%),followed by advanced-study students and interns(81.0%),and cleaning staff (82.4%);HH knowledge awareness rate among HCWs in secondary hospitals was lower than tertia-ry hospitals,and the district-level hospitals had the lowest awareness rate of HH.HH compliance rate and correct rate were 70.1% and 74.9% respectively;the interns and advanced-study students were at a low level of compliance and correct rates (61.4% and 60.9% respectively);the municipal hospitals had the lowest compliance and correct rates,non-teaching hospitals were lower than teaching hospitals.Conclusion HH in primary hospitals is weak,HH of interns,advanced-study students,as well as attendants and cleaning staffs are not enough,HH management should be strengthened,awareness and compliance of HH should be improved.

Objective To explore the behaviors caused by fear of hypoglycemia in type 2 diabetic patients, and deeply analyze the causes of these behaviors, providing help for medical staff to fully understand the inner demands of diabetic patients with hypoglycemia, so as to manage the blood glucose effectively, laying the foundation of Hypoglycemia Fear Survey-behavior scale suitable for domestic type 2 diabetic patients. Methods The interpretative phenomenological analysis method was used guided by the knowledge-attitude-belief-practice and social cognitive theory, 33 patients with hypoglycemia from 5 hospitals with different levels were interviewed by semi-structured interview. Results Four themes were extracted, including excess sensitivity, caution, avoidance and compromise. The theme excess sensitivity contained three kinds of behaviors, that were meal with sensitive alertness, drug sensitivity and excessive response to the hypoglycemia, while the theme caution contained two kinds of behaviors, that were strive to blood sugar stable and must prepare food. Conclusions The results show that the fear of hypoglycemia is serious in type 2 diabetic patients, and they make many behavior change to avoid it, affecting their quality of life and glycemic management. Medical staff should attach importance to the inner feelings and behaviors of diabetic patients with hypoglycemia, and provide guidance and support after comprehensive assessment, working together with the patient to realize the effective management of blood glucose.