Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Research progress and application of donor-derived cell-free DNA in diagnosis and treatment of kidney transplantation / 器官移植

Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a "time window" for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.

Recommendations of severe acute respiratory syndrome coronavirus 2 vaccination in renal transplant recipients / 中华器官移植杂志

As novel coronavirus infection has become a major public health problem affecting human health, vaccination is the most effective means of preventing novel coronavirus infection.Therefore, besides implementing regular epidemic prevention and control, it has become the consensus of international community for effective prevention and control of novel coronavirus infection through accelerating the speed of novel coronavirus vaccination, expanding the scope of vaccination and improving public vaccination rate.Kidney transplant recipients are at an elevated risk of novel coronavirus infection.This population has been in a low immune state for a long time.Thus there are problems such as reduced immunogenicity of COVID-19 vaccine, selection and use of vaccine and breakthrough of infection.Based upon the published international and domestic data, this paper serves as a practical reference for clinicians and healthcare workers to provide consultations to kidney transplant recipients about the administration of novel coronavirus vaccine.

MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter: In vitro and in vivo study

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

EGCG and ECG induce apoptosis and decrease autophagy via the AMPK/mTOR and PI3K/AKT/mTOR pathway in human melanoma cells / 中国天然药物

Catechins have been proven to exert antitumor effects in different kinds of cancers. However, the underlying mechanisms have not been completely clarified yet. This study aimed to assess the effects and mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) on human melanoma skin A375 cells. Results showed that EGCG and ECG inhibited the proliferation of A375 cells and ECG showed better inhibitory effect. Flow cytometry analysis had shown that EGCG and ECG induced apoptosis and led to cell cycle arrest. EGCG and ECG decreased Bcl-2 expression and upregulated Caspase-3 protein level, indicating the development of apoptosis. Furthermore, EGCG and ECG could decreased mitochondrial membrane potential of A375 cells. In addition, the expression of Beclin-1, LC3 and Sirt3 were downregulated at protein levels, which known to be associated with autophagy. After autophagy was increased by rapamycin, the apoptotic trend was not change, indicating that apoptosis and autophagy are independent. Mechanistically, EGCG and ECG treatments decreased phosphorylated-AMPK (p-AMPK) and increased the ratios of p-PI3K, p-AKT and p-mTOR in melanoma cells. Conclusively, EGCG and ECG induced apoptosis via mitochondrial signaling pathway, downregulated autophagy through modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathway. It indicated that EGCG and ECG may be utilized in human melanoma treatment.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial / 中西医结合学报

BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%‍-‍50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).

Clinical analysis of 81 cases of intravenous leiomyomatosis confined to pelvic cavity / 中华妇产科杂志

Objective:To investigate the clinical features, treatment and recurrence factors of intravenous leiomyomatosis (IVL) confined to the pelvic cavity after the operation.Methods:The clinical data of 81 patients who underwent surgery and were pathologically diagnosed with IVL at Women′s Hospital, School of Medicine, Zhejiang University from January 2014 to March 2021, were analyzed retrospectively to explore the influencing factors of postoperative recurrence of IVL, including age, gravidity and parity, surgical methods, intraoperative conditions and so on.Results:(1) Clinical features: the age of 81 IVL patients was (43.9±8.1) years old; increased menstrual volume in 26 cases (32%, 26/81), prolonged menstrual period in 31 cases (38%, 31/81), frequency and urgency to urinate in 4 cases (5%, 4/81), abdominal pain and abdominal distension in 8 cases (10%, 8/81), and pelvic masses in 34 cases (42%, 34/81). IVL was diagnosed right in 4 of 72 patients (6%, 4/72) underwent preoperative ultrasound, right in 11 of 51 patients (22%, 11/51) underwent magnetic resonance imaging (MRI), and right in 4 of 19 patients (4/19) underwent CT. (2) Treatment: all patients with IVL underwent surgical treatment. Surgical procedure: myomectomy in 37 cases, total hysterectomy and bilateral salpingectomy in 19 cases, total hysterectomy and bilateral salpingo-ophorectomy in 25 cases. Surgical approach: hysteroscopic operation in 6 cases, transabdominal operation in 52 cases, laparoscopic operation in 23 cases. Fifty-three cases underwent rapid intraoperative pathological examination, 17 cases (32%, 17/53) of them were diagnosed right as IVL. (3) Influencing factors of IVL postoperative recurrence: among 81 patients with IVL, 3 cases were lost to follow-up, and 8 cases (10%, 8/78) had recurrence during follow-up. Age<35 years, number of pregnancies<2, number of births<2, number of fibroids ≥10, abnormal appearance of fibroids (long, vermicular, beadlike, cystic, etc.) and IVL invasion into adjacent vessels were all the risk factors influencing postoperative recurrence of IVL (all P<0.05). Methods of operation, ovariectomy or not, IVL invasion or not, maximum diameter of IVL, abundant blood vessels near uterine fibroids were not associated with postoperative recurrence of IVL (all P>0.05). Conclusions:The clinical manifestations and preoperative auxiliary examination of IVL are lack of specificity. Doctors need to pay attention to young patients with uterine fibroids, and choose the appropriate surgical scope when the characteristic manifestations of IVL be found during the operation, or the right diagnoses of IVL in the surgery′s rapid intraoperative pathology be examined, and should remove the IVL lesions to reduce the recurrence as far as possible.

Genetic diversity of Sparganum isolates from snakes in Hunan Province based on mitochondrial nad4 and nad5 genes / 中国血吸虫病防治杂志

Objective To investigate the genetic diversity and phylogenetic relationship of Sparganum isolates from snakes in Hunan Province. Methods The partial mitochondrial NADH dehydrogenase subunit 4 (pnad4) and NADH dehydrogenase subunit 5 (pnad5) genes were amplified using a PCR assay in 7 Sparganum isolates from snakes in Hunan Province and the amplification product was sequenced. The homology and genetic evolution were investigated using the software DNAMAN 7.0, MegAlign, DnaSP 5.0 and MEGA 5.0. Results The pnad4 and pnad5 gene sequences were approximately 578 bp and 484 bp in length in the 7 Sparganum isolates from Hunan Province, and the percentages of genetic variations were 0 to 2.8% and 0 to 0.8%, respectively. There were 4 haplotypes detected in both the pnad4 and pnad5 genes, with global haplotype diversities of 0.810 ± 0.016 and 0.905 ± 0.011, nucleotide diversities of 0.006 ± 0.005 and 0.004 ± 0.003, and mean nucleotide variations of 3.960 and 1.905, respectively. Phylogenetic analysis showed that all 7 Sparganum isolates from snakes in Hunan Province were clustered into the same branch with Spirometra erinaceieuropaei isolates from different regions/hosts in the world, which belonged to S. erinaceieuropaei, which were close to Diphyllobothrium latum and far from other tapeworms. Conclusion There is a low genetic variation in snake-derived S. erinaceieuropaei isolates from Hunan Province, and both pnad4 and pnad5 genes may be potential molecular genetic markers for identification of S. erinaceieuropaei.

Study on the effect and mechanism of SKA1 activated by E2F1 transcription in promoting the proliferation of liver cancer cells / 中华内分泌外科杂志

Objective:To investigate whether SKA1 is a key molecule regulating malignant proliferation of liver cancer, and further explore its mechanism to provide molecular theoretical basis for subsequent targeted therapy.Methods:The data of liver cancer from TCGA database were analyzed by bioinformatics technology. The expression of SKA1 in liver cancer was analyzed. At the same time, we also analyzed the relationship between the expression of SKA1 and the prognosis of patients with liver cancer. The hepatoma cell line overexpressing SKA1 was constructed by liposome-mediated cell transfection technique, and the effect of SKA1 on the proliferation of hepatoma cells was further tested by CCK-8 and plate cloning assay. At the same time, we found that E2F1 is also highly expressed in liver cancer, using bioinformatics technology to analyze the correlation between SKA1 and E2F1 expression, further detecting the binding site of E2F1 in the SKA1 promoter region, and using dual luciferase technology to detect E2F1 against SKA1. Transcriptional activation.Results:KA1 was highly expressed in liver cancer tissues, and the overall survival rate of liver cancer patients with high SKA1 expression was 49.8%, lower than that of patients with low SKA1 expression, showing a negative correlation. E2F1 is also highly expressed in liver cancer tissues, and the survival time of patients with liver cancer with high E2F1 expression is significantly lower than that in the low expression group, which was negatively correlated with poor prognosis. SKA1 overexpression could increase the proliferation ability of liver cancer cells by nearly 50%. SKA1 is regulated by the E2F1 transcription factor, and the E2F1 transcription factor is combined with the SKA1 promoter to transcriptionally activate the expression of SKA1 in liver cancer cells.Conclusion:E2F1 transcriptional activation of SKA1 promotes proliferation of hepatoma cells, leading to poor prognosis in patients with liver cancer

Clinical outcomes of neoadjuvant chemotherapy with Gemcitabine and Cisplatin for muscle-invasive bladder cancer / 国际外科学杂志

Objective:To investigate the clinical outcomes of neoadjuvant chemotherapy with Gemcitabine and Cisplatin (GC) for muscle-invasive bladder cancer (MIBC).Methods:Retrospective analysis of 67 MIBC patients admitted to Beijing Friendship Hospital, Capital Medical University from December 2010 to June 2020. Fifty-five MIBC patients (cT2-T4aN0M0) underwent GC plus radical cystectomy-pelvic lymph node dissection. Pathological responses, prognosis and chemotherapy toxicities were analyzed. The Chi-square test and Fisher′s exact probability method were used to compare the count data between groups. The overall survival (OS) and disease-free survival (DFS) were based on the Kaplan-Meier survival curve, and the Log-rank test was used to evaluate the difference between groups in the survival curve. Prognostic analysis adopts Cox proportional hazards regression model.Results:Fifty-five MIBC patients received GC plus radical cystectomy-pelvic lymph node dissection. The 81.8% patients ( n=45) received 2 cycles GC and 18.2% patients ( n=10) received 3 cycles. The complete pathological response (pT0N0M0) rate was 30.9% ( n=17) and partial response (pT 1/Tis/T aN 0M 0) rate was 10.9% ( n=6). Overall pathological response rate was 41.8%. The median follow-up was (47.0±37.7) months, 5-year OS were 82.2% and 22.1% (<pT 2 versus ≥pT 2, P<0.001), and DFS were 86.1% and 32.1% (<pT 2 versus ≥pT 2, P<0.001). Pathological response and positive lymph nodes were independent risk factors of overall survival and disease-free survival on multivariable analysis ( P<0.05). The most common chemotherapy toxicities were hematologic toxicities and gastrointestinal reactions, and none delayed surgery due to toxicities. Conclusion:Neoadjuvant GC plus radical cystectomy-pelvic lymph node dissection has a significant clinical benefit in MIBC patents and chemotherapy toxicities are well tolerated.

Two Serum Free Light Chain Detection Systems in the Diagnosis of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) .@*METHODS@#Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression.@*RESULTS@#Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ：36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (｜FLC-κ- FLC-λ｜) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range.@*CONCLUSION@#Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.

Analysis on the concentration of chloroform and risk factors of swimming pools in Bao’an District of Shenzhen City / 上海预防医学

Objective:To investigate the concentration level of chloroform in the water of swimming pool in Baoan District of Shenzhen City，and determine the risk factors. Methods:During May and July，2019，a total of 110 water samples from 40 swimming pools were collected in Xin’an subdistrict of Bao’an District for the examination of chloroform routine indicators. In addition， 38 pipe water samples were collected for the examination of chloroform and free residual chlorine． Results:The concentration of chloroform in the swimming pools was determined to be （43.400±27.802） μg/L with the median of 37.343 μg/L. Chloroform was correlated positively with total bacterial count（P<0.05），turbidity， free chlorine residual， and PH value（P<0.01）. Conclusion:The disinfection quality of swimming pool water in Bao’an District remains low. It is necessary to determine the risk factors associated with chloroform in the swimming pool and further reduce the concentration level of disinfection by-products.

Evaluating the effect of midpalatal corticotomy-assisted rapid maxillary expansion on the upper airway in young adults using computational fluid dynamics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Midpalatal corticotomy-assisted rapid maxillary expansion (MCRME) is a minimally invasive treatment of maxillary transverse deficiency (MTD) in young adults. However, the effect of MCRME on respiratory function still needs to be determined. In this study, we evaluated the changes in maxillary morphology and the upper airway following MCRME using computational fluid dynamics (CFD). Twenty patients with MTD (8 males, 12 females; mean age 20.55 years) had cone-beam computed tomography (CBCT) images taken before and after MCRME. The CBCT data were used to construct a three-dimensional (3D) upper airway model. The upper airway flow characteristics were simulated using CFD, and measurements were made based on the CBCT images and CFD. The results showed that the widths of the palatal bone and nasal cavity, and the intermolar width were increased significantly after MCRME. The volume of the nasal cavity and nasopharynx increased significantly, while there were no obvious changes in the volumes of the oropharynx and hypopharynx. CFD simulation of the upper airway showed that the pressure drop and maximum velocity of the upper airway decreased significantly after treatment. Our results suggest that in these young adults with MTD, increasing the maxillary width, upper airway volume, and quantity of airflow by MCRME substantially improved upper airway ventilation.

TRPV4 channel mediates the increase of pulmonary microvascular endothelial permeability in rats with chronic hypoxic pulmonary hypertension / 生理学报

The purpose of the present study was to investigate the effect of transient receptor potential vanilloid 4 (TRPV4) channel on the permeability of pulmonary microvascular endothelial cells (PMVECs) in rats with chronic hypoxia-induced pulmonary hypertension (CHPH), so as to clarify the mechanism of vascular endothelial dysfunction during the occurrence of pulmonary hypertension (PH). CHPH rat model was established by exposure to chronic hypoxia (CH) for 21 days. Primary PMVECs were cultured by adherent tissue blocks at the edge of the lung. The permeability coefficient of primary cultured PMVECs was detected by fluorescein isothiocyanate (FITC)-dextran. The structure of tight junction (TJ) was observed by transmission electron microscope. The expression of TRPV4 and TJ-related proteins, such as, Occludin, Claudin-5, ZO-1 were examined by real-time fluorescence quantitative PCR and Western blotting. The intracellular calcium concentration ([Ca

Progress in the construction and screening of random mutation library / 生物工程学报

Directed evolution is a cyclic process that alternates between constructing different genes and screening functional gene variants. It has been widely used in optimization and analysis of DNA sequence, gene function and protein structure. It includes random gene libraries construction, gene expression in suitable hosts and mutant libraries screening. The key to construct gene library is the storage capacity and mutation diversity, to screen is high sensitivity and high throughput. This review discusses the latest advances in directed evolution. These new technologies greatly accelerate and simplify the traditional directional evolution process and promote the development of directed evolution.

Analysis of Health Service Utilization and its Influencing Factors among Patients with Pneumoconiosis in China / 生物医学与环境科学（英文）

Pneumoconiosis, an interstitial lung disease that occurs from breathing in certain kinds of damaging dust particles, is a major occupational disease in China. Patients diagnosed with occupational pneumoconiosis can avail of free medical treatment, whereas patients without a diagnosis of occupational diseases cannot not claim free medical treatment in most provinces from the government before 2019. This study aimed to analyze the priority of medical facility selection and its influencing factors among patients with pneumoconiosis. A total of 1,037 patients with pneumoconiosis from nine provinces in China were investigated. The health service institutions most frequently selected by the patients were county-level hospitals (37.5%). The main reason for the choice was these hospitals' close distance to the patients' homes (47.3%). The factors for the choice of health care institutions were living in the eastern region (

Effects of 4-hydroxy-2（3H）-benzoxazolone on Inflammatory and Apoptosis Signaling Pathways in Non-alcoholic Fatty Liver Disease Model Rats / 中国药房

OBJECTIVE：To inv estigate the effects of 4-hydroxy-2（3H）-benzoxazolone on inflammatory and apoptosis signaling pathways in non-alcoholic fatty liver disease （NAFLD）model rats. METHODS ：SD rats were divided into normal control group（10 rats）and modeling group （50 rats）. Normal control group was given basic diet ，and modeling group were given high-fat diet to induce NAFLD model. After modeling ，the rats were divided into normal control group ，model group ，silibinin group （26.25 mg/kg），and 4-hydroxy-2（3H）-benzoxazolone high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 8 rats in each group. Normal control group and modeling group were given 0.6％ CMC-Na intragastrically ，and other groups were given relevant medicine 10 mL/kg intragastrically ，once a day ，for consecutive 4 weeks. After last medication ，the serum levels of albumin（ALB），total protein （TP），globulin（GLB），ALB/GLB and free fatty acid （FFA）were detected ；TUNEL staining was used to observe the apoptosis of rat hepatocytes. Western blot assay was used to detect the protein expression and phosphorylation level of inflammatory signaling pathway related proteins [Toll-like receptor 4（TLR4），myeloid differentiation factor 88（MyD88）， nuclear factor-κB p65（NF-κB p65），NF-κB inhibitor protein（IκBα）] in liver tissue as well as the expression of apoptosis signaling pathway related proteins [B cell lymphoma 2（Bcl-2），Bax，caspase-3]. RESULTS ：Compared with model group ，serum levels of TP （except for low-dose group ），GLB and FFA ，the protein expression of TLR 4（except for low-dose group ），MyD88 （except for medium-dose group ）and caspase- 3，the phosphorylation levels of NF-κB p65 and IκBα protein were decreased significantly（P＜0.05 or P＜0.01）. The ratio of A LB/GLB in serum and the ratio of Bcl- 2/Bax in liver tissue were significantly increased（P＜0.05 or P＜0.01），and the phenomenon of hepatocyte apoptosis was improved. CONCLUSIONS ：4-hydroxy-2 （3H）-benzoxazolone can ameliorate NAFLD in rats ，and the mechanism may be associated with inhibiting the expression TLR 4/ MyD88/NF-κB signaling pathway-related proteins and apoptosis-related proteins in liver tissues.

Methodological Research on Rapid Detection and Genotyping of NPM1 Gene Mutations in Leukemia / 中国实验血液学杂志

OBJECTIVE@#To establish a method for rapid detection and typing of NPM1 mutations in acute myeloid leukemia (AML) by fluorescence melting curve analysis technology.@*METHODS@#A pair of primers and a fluorescent single-stranded probe (molecule beacon) were designed for the mutant genes mutA, mutB, mutD in exon 12 of nucleopsin (NPM1) and wild type. With a real-time qPCR, the A, B, and D gene mutations of NPM1 were detected and typed by different-melting curve peak value of the probe through RT-PCR.@*RESULTS@#This method could detected the mutations of A, B, and D in NPM1 effectively with a sensitivity of 1%. Furthermore, 62 AML clinical samples were evaluated by the method. In the results, the detection rate and typing of NPM1 mutations were consistent with the sequencing results of clinical samples.@*CONCLUSION@#There are three features in the method of fluorescence melting curve analysis: stable PCR system, easy to operate, and the easily distinguishable results. The method might meet the demand for rapid typing of NPM1 gene mutation in early diagnosis or concomitant diagnosis of AML.

Clinical efficacy of counterclockwise rotating the functional occlusal plane using micro-implant anchorage / 浙江大学学报·医学版

To evaluate the therapeutic effect of using micro-implant anchorage (MIA) to rotate the functional occlusal plane (FOP) counterclockwise. Forty skeletal class Ⅱ high-angle patients who had completed orthodontic treatment were enrolled, including 20 patients treated with MIA orthodontic system (MIA group) and the other 20 patients treated with traditional sliding straight wire appliance (control group). Cephalometric measurements on the lateral cranial radiographs before and after treatment were performed, all acquired data were statistically analyzed with SPSS 26.0. At the end of treatment, MIA group obtained better effect of FOP and mandibular plane counter-clockwise rotation than the control group. In the MIA group, the average change of FOP-frankfort horizontal plane (FH), FOP-SN and mandibular plane angle (MP-FH) angle was -4.5(-7.3, -3.7)°, (3.3)° and -1.7(-3.0, -0.9)°, respectively. In the control group, the average change of FOP-FH, FOP-SN and MP-FH angle was -0.1(-4.1, 3.0)°, (-0.1±5.1)° and -0.4(-2.4, 0.7)°, respectively. There was significant difference between the change of the two groups (all <0.05). Compared with the traditional sliding straight wire appliance, counterclockwise rotation of FOP can be more effectively reversed by using MIA orthodontic system, and the MP-FH can be reduced as well.