Objective To establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)for the simultaneous determination of gefitinib,erlotinib,nillotinib and imatinib plasma concentrations and analyze the results.Methods The plasma samples were treated with acetonitrile precipitation and separated by Diamonsil C18 column(150 mm ×4.6 mm,3.5 μm)with mobile phase of 0.1％formic acid water(A)-0.1％formic acid acetonitrile(B).The flow rate of gradient elution was 0.7 mL·min-1,and the column temperature was 40 ℃ and the injection volume was 3 μL.Using arotinib as the internal standard,the scanning was carried out by using electrospray ionization source in positive ionization mode with multi-reaction monitoring.The specificity,standard curve,lower limit of quantitation,precision,accuracy,recovery rate,matrix effect and stability of the method were investigated.The concentrations of imatinib and erlotinib in 20 patients with chronic myelogenous leukemia(CML)and gefitinib and erlotinib in 3 patients with non-small cell lung cancer were measured.Results The standard curves of the four drugs were as follows,gefitinib:y=2.536 × 10-3x+9.362 × 10-3(linear range 20-2 000 ng·mL-1,R2=0.996 6);erlotinib:y=3.575× 10-3x+7.406 × 10-3(linear range 50-5 000 ng·mL-1,R2=0.994 9);nilotinib:y=1.945 x 10-3x+0.015 643(linear range 50-5 000 ng·mL-1,R2=0.990 6);imatinib:y=4.56 x 10-3x+0.010 451(linear range 100～104 ng·mL-1,R2=0.9963).RSD of intra-day and inter-day were less than 10％,and the accuracy ranged from 90％to 110％,and the recovery rates were 91.35％to 98.93％(RSD＜10％);the matrix effect ranged from 91.64％to 107.50％(RSD＜10％).Determination of 23 patients showed that the blood concentration of nilotinib ranged from 623.76 to 2 934.13 ng·mL-1,and the blood concentration of imatinib ranged from 757.77 to 2 637.71 ng·mL-1,and the blood concentration of gefitinib ranged from 214.76 to 387.40 ng·mL-1.The serum concentration of erlotinib was 569.57 ng·mL-1.Conclusion The method of this research is simple,fast,sensitive and dedicated,which can be monitored by the concentration of clinical blood.

[Abstract] Objective To investigate the relationship between the Han, Zhuang and the World populations by comparing the frequency of dental non-metric traits. Methods From 2015 to 2019, ten dental non-metric traits were sampled from He’nan, Jiangsu and Guangxi Zhuang Autonmous Region, with sample size of 1785(674 He’ nan, 547 Jiangsu, 388 Guangxi Han, 176 Guangxi Zhuang). Principal component analysis, multidimensional scaling and neighbor network were carried out. Results East Asian populations could be clearly divided into two major groups, Northeast Asian and Southeast Asian. Han and Zhuang populations were close to the Northeast Asian populations, but were far from the Southeast Asian populations. There were also some north-south differences within Han populations. Conclusion Both Sundadonty and Sinodonty are existed in East Asian populations. Han and Zhuang populations dental non-metric traits are closer to the Sinodonty.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML). METHODS: The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m² /d×3 d). RESULTS: Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019). CONCLUSION Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.
Male ; Female ; Humans ; Decitabine ; Retrospective Studies ; Transplantation, Homologous/adverse effects* ; Transplantation Conditioning/adverse effects* ; Myelodysplastic Syndromes/complications* ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Chronic Disease ; Graft vs Host Disease/therapy* ; Recurrence

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER NCT03620565, https://register.clinicaltrials.gov.
China ; Female ; Gynecologic Surgical Procedures/adverse effects* ; Humans ; Pelvic Floor/surgery* ; Pelvic Organ Prolapse/surgery* ; Surgical Mesh/adverse effects* ; Treatment Outcome ; Vagina

To explore the application of radiomic analysis in differential diagnosis of renal cell carcinoma in patients with hydronephrosis and renal calculi using supervised machine learning methods.The abdominal CT scan data were retrospectively analyzed for 66 patients with pathologically confirmed hydronephrosis and renal calculi, among whom 35 patients had renal cell carcinoma. In each case 18 non-texture features and 344 texture features were extracted from the region of interest (ROI). Infinite feature selection (InfFS)-based forward feature selection method coupled with support vector machine (SVM) classifier was used to select the optimal feature subset. SVM was trained and performed the prediction using the selected feature subset to classify whether hydronephrosis with renal calculi was associated with renal cell carcinoma.A total of 12 texture features were selected as the optimal features. The area under curve (AUC), accuracy, sensitivity, specificity, false positive rate and false negative rate of the SVM- InfFS model for predicting accompanying renal tumors in patients with hydronephrosis and calculi were 0.907, 81.0%, 70.0%, 90.9%, 9.1%, and 30.0%, respectively. The diagnostic accuracy, sensitivity, specificity, false positive and false negative rates by the clinicians provided with these classification results were 90.5%, 80.0%, 100%, 0.00%, and 20.0%, respectively.The computer-aided classification model based on supervised machine learning can effectively extract the diagnostic information and improve the diagnostic rate of renal cell carcinoma associated with hydronephrosis and renal calculi.
Carcinoma, Renal Cell ; diagnosis ; Diagnosis, Differential ; Humans ; Hydronephrosis ; diagnosis ; Kidney Calculi ; Kidney Neoplasms ; diagnosis ; Retrospective Studies

Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.
Adrenomedullin ; metabolism ; Animals ; Blood Pressure ; drug effects ; physiology ; Hypertension ; etiology ; Lipopolysaccharides ; pharmacology ; Male ; Neuropeptides ; metabolism ; Obesity ; complications ; Rats, Sprague-Dawley ; Receptors, Adrenomedullin ; drug effects ; metabolism ; Sympathetic Nervous System ; drug effects ; metabolism ; Toll-Like Receptor 4 ; metabolism

Objective To investigate the diagnostic value of pyruvate kinase M2 ( PKM2) gene expression in papillary thyroid carcinoma ( PTC). Methods Quantitative real-time PCR ( RT-qPCR) was used to detect the expression of PKM2 mRNA in benign thyroid nodules, PTC, and normal thyroid cells around nodules of fine-needle aspiration (FNA) specimens. Immunohistochemistry ( IHC) was used to detect the expression of PKM2 protein in thyroid tissue after thyroidectomy. The receiver operating characteristic curve was constructed to evaluate the diagnostic value of PKM2 in PTC. Results The expression of PKM2 mRNA was detectable in FNA specimens of thyroid nodules,higher in PTC than those in normal thyroid tissue and benign thyroid nodules (P<0.01). PKM2 expression level was correlated with diameter of PTC ( P<0.05) , but had no correlation with lymph node metastasis, BRAFV600E mutation, and American Joint Committe on Cancer( AJCC) stage ( P>0.05) . The expression level of PKM2 mRNA in FNA specimens of thyroid nodules was paralleled with the expression level of PKM2 protein in postoperation pathological tissues. The accuracy, sensitivity, specificity of PKM2 gene in the diagnosis of PTC were 62.8％, 46.9％, and 95.7％, respectively. The accuracy and sensitivity of PKM2 combined with BRAFV600E were increased to 87.6％and 83.7％. Conclusion Detection of PKM2 gene in FNA specimens is highly specific in the diagnosis of PTC, making it a valuable molecular marker for preoperative diagnosis. The combination of PKM2 and BRAFV600E detection shows a higher diagnosis efficiency.

Objective To investigate the current situation of empathy and self-efficacy, and relation with perform-ance of objective structured clinical examination in residents of standardized training. Methods Questionnaire sur-veys with Jefferson scale of empathy health professionals and general self-efficacy scale were conducted among resi-dents of grade 2015 and grade 2016 from department of internal medicine of Peking Union Medical College Hospital (PUMCH). Results Totally 101 questionnaires were delivered,and 99 were collected back. The average empathy score was 111.3±1.2,with that of grade 2015 slightly higher than that of grade 2016. The empathy score from resi-dents of different degree and different sources showed no significant difference. The average self-efficacy score was 22.77±0.50. The score of residents of grade 2015 was significantly higher than that of grade 2016. The score was higher in residents with higher degree. The score of residents from PUMCH was higher than the other subgroups. The score of empathy showed no significant correlation with OSCE scores, while the score of self-efficacy of resi-dents of grade 2015 significantly positively correlated with scores of medical recording (R=0.35,P<0.05),case analyzing (R=0.31,P<0.05) and average score(R=0.33,P<0.05) of OSCE. Conclusions The empathy and self-efficacy of residents remained to be improved, and could be improved through clinical training. Psychological evaluation could be inducted into standardized resident training system,and provide helpful supplementary to OSCE with more comprehensive evaluation of residents.

Objective To observe the effects of Qijingmingmu decoction granule on the expression of mitogen-activated protein linase (MAPK) signal pathway in fibroblasts of conjunctivochalasis (CCH) under the stimulation of tumor necrosis factor (TNF-α) and to explore the pathogenesis and effective treatment method of CCH.Methods CCH conjunctival fibroblasts were cultured in vitro and divided into CCH group,CCH + TNF-α group and CCH + TNF-α + Qijingmingmu decoction group.CCK-8 assay was used to determine the effective concentration of Qijingmingmu decoction granule,and 10-2 mg · L-1 TNF-α was added in the cultured fibroblasts of the latter two groups,followed by interference with Qijingmingmu decoction granule for 48h.The expression of MAPK signal pathway related protein and mRNA were detected by ELISA,Western Blot and RT-PCR.Then the results were statistically analyzed.Results CCK-8 assay showed the effective concentration of Qijingmingmu decoction granule was 1.61g · L-1.And there were significant differences in the total A values (A450) of extracellular regulated protein kinase (ERK),c-jun N-terminal kinase (JNK),p38 mitogen activated protein kinase (p38 MAPK) and their phosphorylation levels among the three groups (all P ＜ 0.05).Moreover,TNF-α could significantly up-regulate the expression of ERK1/2,JNK1/2,p-JNK1/2,p38 MAPK and p-p38 MAPK in CCH fibroblasts (all P ＜0.05),while Qijingmingmu decoction down-regulated their expressions in CCK fibroblasts after TNF-α stimulation (all P ＜ 0.05).Furthermore,the total differences in p-ERK1/2,p38 MAPK and p-p38 MAPK protein were significant in the three groups (all P＜0.05);and TNF-α could significantly up-regulate the expression of p-ERK1/2,p-JNK1/2,p38 MAPK and p-p38 MAPK protein in CCH fibroblasts (all P ＜0.05),while Qijingmingmu decoction down-regulated p-ERK1/2 and p38 MAPK expressions in CCK fibroblasts after TNF-α stimulation (both P ＜ 0.05).In addition,the total differences in ERK1/2 and p38 MAPK mRNA were significant in the three groups (both P ＜ 0.05);and TNF-α could significantly up-regulate the expression of ERK1/2 and p38 MAPK mRNA in CCH fibroblasts (both P ＜ 0.05),while Qijingmingmu decoction down-regulated p38 MAPK mRNA expressions in CCK fibroblasts after TNF-α stimulation (P ＜ 0.05).Conclusion The inflammatory factor TNF-α can up-regulate the expressions of MAPK signal pathway related protein and mRNA in CCH fibroblasts,resulting in the occurrence and development of CCH,and meanwhile Qijingmingmu decoction granule can downregulate the expression of MAPK signal pathway to play the therapeutic role in CCH to some extent.