[Echocardiographic two-dimensional strain evaluation of right ventricular function in healthy adults].

Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

[Clinical features of patients with Rhupus syndrome].

OBJECTIVE: To investigate the clinical and serological features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) overlap syndrome (Rhupus syndrome). METHODS: We retrospectively reviewed the medical records of 21 patients with Rhupus syndrome who were hospitalized at Department of Rheumatology and Immunology, People's Hospital of Xinjiang Uygur Autonomous Region between January 2010 and January 2018. We compared the joint involvement, autoantibodies and clinical manifestations of Rhupus syndrome with 81 cases of RA-alone and 51 cases of SLE-alone. RESULTS: In 21 patients with Rhupus syndrome, there are 3 males and 18 females. Compared with the SLE-alone group, the patients with Rhupus syndrome were older [(49.43±11.66) vs. (40.59±12.73), P=0.008]. The median age of the patients with Rhupus syndrome at RA onset was significantly younger than that of the RA-alone patients [(32.58±11.14) vs. (43.11±11.83), P=0.010]. Of the 21 patients with Rhupus syndrome, the initial diagnosis was RA in 57% (12/21), except 2 male patients, the other 10 patients with SLE manifestations were menopause, the mean age of amenorrhea or menopause was (44.30±5.33) (36-50) years. The mean interval between the onset of SLE and RA was 10.83 years. Two patients started with SLE manifestations. Moreover, both diseases simultaneously developed in 33.3% of the patients. Except one male patient, 3 patients were in menopause stage when RA and SLE appeared. The positive rate of specific antibody Rhupus syndrome was similar to that of RA. Renal damage was relatively rare in SLE related manifestations, but the incidence of interstitial lung disease was higher. There were no significant differences in the prevalence of complements C3 and C4, antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-SSA or anti-SSB antibody between the Rhupus syndrome and SLE-alone group. CONCLUSION: Rhupus syndrome is an overlapping syndrome in which RA and SLE coexist. Most of the diseases occur in RA and the related manifestations of RA are more serious than those of SLE. The incidence of Rhupus syndrome may be related to the change of sex hormone levels.

[The clinical significance of serum autoantibodies and HLA-B(27) molecule testing in Uygur patients with human immunodeficiency virus infection].

Objective: To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B(27)) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection. Method: A total of 727 HIV-infected Uygur patients who visited Kuche infectious diseases hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA), anti-cyclic citrullinated peptide (CCP) antibody, anti-extractable nuclear antigen (ENAs) antibody and HLA-B(27) molecule were tested. Result: Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05) years. There were 697 (95.87%) patients receiving highly active antiretroviral therapy (HAART) with mean duration of treatment (5.52±3.47) years. The mean CD4(+)T cell count was (520±271) cells/µl in 202 HIV-infected patients, and mean virus load was (108 139±20 498) copies/ml in 20 HIV-infected patients. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%) , alopecia (9.90%) , arthralgia (8.94%) , ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.43% vs. 17.43%, P<0.001) with low titers (ANA titer:1∶100) . HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (32.71% vs. 50.00%, P=0.049). There were no correlations between ANA and duration of HAART, CD4(+)T cell counts and virus load (r values 0.061, 0.047, 0.121, respectively. P>0.05). Only one female patient was HLA-B(27) positive (0.14%), which was significantly lower than that in healthy controls (3.08%) (P<0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA). Conclusion: Autoimmune manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It's noted that patients with autoimmune manifestations should be considered as a differential diagnosis of HIV infection.

[Influence of Halogenated Hydroxyl-Alkanes Inhalation Anesthetic on the Determination of Ethanol Content in Blood].

ABSTRACT: Objective To study the influence of halogenated hydroxyl-alkanes inhalation anesthetic on the determination of ethanol content in blood. Methods Halogenated hydroxyl-alkanes were analyzed by headspace gas chromatography with double column confirmatory detection method. The influence of halogenated hydroxyl-alkanes on determination of ethanol content in blood sample by headspace gas chromatography was explored under the different detection conditions of KB-BAC1/ KB-BAC2 and J&W DB-ALC1/DB-ALC2 gas chromatographic column. Results The retention time of sevoflurane and enflurane was similar to that of ethanol and tert butanol respectively when using the J&W DB-ALC1/DB-ALC2 gas chromatographic column, and interfered with the detection of ethanol content in blood; only J&W DB-ALC1 gas chromatographic column can separate the sevoflurane and ethanol components, so as to eliminate their influence on the detection of ethanol content in blood. When using KB-BAC1/KB-BAC2 gas chromatographic column, the retention time of sevoflurane, isoflurane and ethanol is similar, especially that of sevoflurane and ethanol, and sevoflurane obviously interferes with the determination of ethanol content in blood. Conclusion Halogenated hydroxy-alkanes interfere with determination of ethanol content in blood by headspace gas chromatography. The interference can be discriminated effectively by choosing the suitable chromatographic column and double column confirmatory detection.

[Evaluation of menopause and treatment choice of breast cancer patients before endocrine therapy].

Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.

[The diagnostic value of serum KL-6 in connective tissue disease associated interstitial lung disease].

Objective: To evaluate the diagnostic value of the serum Krebs von den Lungen-6 (KL-6) for the interstitial lung disease associated with connective tissue diseases (CTD-ILD). Methods: 84 patients with CTD-ILD (CTD-ILD group) and 91 patients with connective tissue disease (CTD group) who visited the department of rheumatology and immunology of People's Hospital of Xinjiang Uygur Autonomous Region between January, 2016 and December, 2017 were included. Serum KL-6 levels were measured by commercially available enzyme linked immunosorbent assay (ELISA) kits. Results: The significantly higher levels of KL-6 were determined in the CTD-ILD group than CTD group [1 239 (577, 2 094) vs 152 (89, 280) U/ml] (P<0.001). The optimal cutoff value of serum KL-6 for diagnosis of CTD-ILD was 402 U/ml, and the sensitivity and specificity were 82.1% and 86.8%, respectively. Area Under the Curve (AUC) was 0.905. Logistic regression analysis revealed that elevated KL-6 and decreased Carbon monoxide diffusion capacity were independently correlated with the occurrence of CTD-ILD, the decreased of DLcoSB% (OR=0.928, 95%CI: 0.891-0.968) and increase of KL-6 level (OR=1.005, 95%CI: 1.003-1.007) was the independent risk factor for the occurrence of ILD. Conclusion: The serum KL-6 is an important biomarker for the diagnosis of CTD-ILD and when the level of KL-6 is increased, the ILD should be alert.

[Effects of different drugs on bronchial stenosis by TGF-ß/mTOR signaling pathway in rabbit model].

Objective: To investigate the effect of different drugs on tracheal stenosis caused by transforming growth factor-ß/rapamycin target protein (TGF-ß/mTOR) signaling pathway. Methods: Thirty rabbits were randomly divided into normal control group, normal saline group, penicillin group, budesonide group and erythromycin group. The normal control group was not treated,and tracheal stenosis models were established in the other groups. From the 1st to 10th day after modeling, each group was respectively administered with normal saline (0.75 ml/kg, 2 times/d), intramuscular injection of penicillin (40 000 U/kg, 2 times/d), gastric administration of erythromycin (12.5 mg/kg, 2 times/d), inhalation of budesonide (0.05 mg/kg, 2 times/d). Rabbits were sacrificed on the 11th day after surgery, and tracheal specimens were collected to measure the degree of tracheal stenosis. Relative mRNA expression level of interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß), Type Ⅰ collagen (COL-1), Type Ⅲ collagen (COL-3), and Sirtuin 1 (SIRT-1) were detected by Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR); protein expression of mTOR, phosphorylated protein kinase B (p-AKT), vascular endothelial growth factor (VEGF),SIRT-1 were detected by immunohistochemical analysis; protein expression of nuclear factor κB (NF-κB),phosphorylated nuclear factor κB (p-NF-κB),protein kinase B (AKT),p-AKT,mTOR were detected by Western blotting. Results: The degree of stenosis of normal control group was (14.02±2.86)%, saline group was (64.14±3.21)%, penicillin group was (49.11±2.96)%, budesonide group was (39.52±2.09)%, erythromycin group was (32.60±4.27)%. The differences between any two groups were statistically significant (all P<0.05). Except between erythromycin group and normal control group, the differences in relative expression of IL-6 mRNA between any two groups (1.00±0.00, 9.02±1.50, 4.25±0.87, 2.53±0.17, 1.31±0.56) was statistically significant (all P<0.05), and the differences in relative expression of TGF-ß mRNA among all groups (1.00±0.00, 6.92±0.84, 3.83±0.44, 2.13±0.25, 1.40±0.15) were statistically significant (all P<0.05). The relative expression of SIRT-1 mRNA among all the groups (1.000±0.000, 0.209±0.042, 0.375±0.034, 0.555±0.028, 0.667±0.032) was statistically significant different (all P<0.05); except between erythromycin group and budesonide group,the protein levels of SIRT-1 among all other groups (16.93±2.28, 4.77±1.45, 7.70±0.61, 10.76±1.04, 11.03±1.10) were statistically significant different (all P<0.05). The protein levels of mTOR (9.28±4.56, 58.18±8.12, 44.75±5.56, 32.82±5.99, 24.73±3.56) and p-AKT (16.57±4.86, 61.79±6.66, 42.98±5.99, 32.79±5.34, 24.00±4.40) determined through immunohistochemistry of all groups were statistically significant different (all P<0.05). The protein levels of NF-κB, p-NF-κB, AKT, p-AKT and mTOR determined through Western blotting had the same trend as that of determined through immunohistochemistry. The protein expression of NF-κB,AKT and mTOR in saline group were significantly higher than other groups; those protein expression of erythromycin group was lower than budesonide group and penicillin group. Except between the erythromycin group and the normal control group, the protein expression of mTOR in other groups was statistically significant different (all P<0.05). Conclusion: Penicillin,erythromycin and budesonide can alleviate inflammation by increasing SIRT-1, alleviate tracheal scar hyperplasia induced by TGF-beta/mTOR pathway, and reduce the degree of tracheal stenosis in rabbits.

[Diagnosis and treatment of osteoblastic metastasis in patients with breast cancer].

Osteoblastic metastasis of breast cancer is relatively rare, but there are cases of misdiagnosis and mistreatment in clinical treatment. They can only be diagnosed by X ray or CT bone scan and must be identified from bone repair after effective treatment in patients with osteolytic or mixed bone metastases. Bone metastasis is often seen in the disease-free condition of breast cancer, and very few can occur in stage Ⅳ lesions prior to surgery. Based on the analysis of clinical phenomena, we questioned the evaluation criteria of the therapeutic effect on bone metastasis of breast cancer created by the World Health Organization and the MD Anderson Cancer Center and concluded the formation mechanism of bone metastasis. For patients with simple osteoblastic bone metastasis, we broke through the recommendations of the National Comprehensive Cancer Network guideline and advocated the concept of "noninterference" . Patients with positive hormone receptor can be treated with traditional endocrine therapy. Hormone receptor negative and/or human epidermal growth factor receptor 2 positive patients can be observed first, followed by chemotherapy and/or targeted therapy when there is osteolytic bone metastasis or visceral metastasis. Furthermore, bisphosphonates are not required since osteoblastic bone metastasis is generally not associated with the risk of bone related events. The active treatment of primary lesion should be taken into account in stage Ⅳ patient before operation.

[Clinical value of endoscopicultrsaonography and multi-slice spiral CT in Siewert â ¡and â ¢ type adenocarcinoma of esophagogastric junction].

Objective: To investigate the clinical value of endoscopic ultrasonography (EUS) and Multi-slice Spiral CT (MSCT) in the preoperativestaging of tumor(T) and lymph node (N) metastasis in patients with SiewertⅡand Ⅲ typeadenocarcinoma of esophagogastric junction(AEG). Methods: Clinical data of 145 Siewert Ⅱ and Ⅲ type AEG patientswithout preoperative chemoradiotherapy were retrospectively reviewed. Theyall received preoperative EUS and MSCT examination and underwent surgical resection, and the results of EUS and MSCT were compared with their postoperative pathologic staging. Results: The sensitivity, specificity, and accuracy of EUS for T stage in Siewert Ⅱ and Ⅲ type AEG were higher than those of MSCT. The total accuracy of EUS and MSCT were 90.3% and 63.5%, respectively, and the difference was statistically significant (χ(2)=29.52, P<0.01). The sensitivity of EUS for T1, T2 and T3 were 89.5%, 91.1% and 85.2%, respectively, which were significantly higher than 42.1%, 66.7% and 29.6% of MSCT (χ(2)=9.47, P<0.01 for T1; χ(2)=8.07, P<0.01 for T2; χ(2)=17.40, P<0.01 for T3). In addition, the total accuracy of EUS and MSCT for lymph node metastasis status of Siewert Ⅱ and Ⅲ type AEG were 75.9% and 64.8%, respectively, showing a statistically significant difference(χ(2)=4.23, P=0.04). The sensitivity of EUS for N1 and N2 were 82.1% and 79.2%, respectively, which were significantly higher than 53.6% and 60.4% of MSCT (χ(2)=5.24, P=0.02; χ(2)=4.48, P=0.03). There was no statistical significance for sensitivity of EUS and MSCT in N0 and N3 (P>0.05). Conclusion: EUS diagnosis of T and N staging in Siewert Ⅱ/Ⅲ type AEG showed significantly greater performance than MSCT.

[Evaluation and classification of drug therapy for breast cancer with bone-only metastasis].

Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

[Expression and significance of autophagy in rabbit model of tracheal stenosis].

Objective: To investigate the expression and significance of autophagy in rabbit model of tracheal stenosis. Methods: A total of 18 rabbits were equally divided into 3 groups (blank control group, saline group, erythromycin group) in accordance with the random number table. After rabbit model of tracheal stenosis was established, no treatment was done with blank control group. Saline group was atomized with saline (0.54 mg/kg, 2 times/day), and erythromycin group was fed on erythromycin (7.5 mg/kg, 2 times/day) for 7 days before and 10 days after the operation. On the eleventh day, rabbits were executed, and their trachea were collected. The proportion of collagen fiber area of tracheal lamina propria (LP) and epithelium (EP) was assessed by Masson staining. The mRNA of autophagy associated gene-3 (ATG3) and autophagy associated gene-5 (ATG5) of tracheal mucosa were assessed by Real-Time Polymerase Chain Reaction (RT-PCR). The protein of microtubule-associated protein 1 light chain ß(3) (LC3B), ATG3 and ATG5 were assessed by Western blot. Results: The proportion of collagen fiber area of tracheal LP and EP of blank control group was (6.79±0.67)%, saline group was (40.55±5.40)%, erythromycin group was (27.48±0.43)%. The differences between any two groups was all statistically significant (all P<0.01). The relative value of ATG3 mRNA and ATG5 mRNA in saline group were significantly lower than blank control group (all P<0.01). Those value in erythromycin group were significantly higher than the saline group (all P<0.01). The protein levels of LC3B-Ⅱ/Ⅰ, ATG3 and ATG5 in saline group were significantly lower than blank control group (all P<0.01). After low dose of erythromycin intervention, all the protein levels were significantly higher than the saline group (all P<0.01). Conclusions: The expression of autophagy is decreased in rabbit model of trachea stenosis. Low dose of erythromycin could increase the expression of autophagy and at the same time alleviate the degree of fibrosis of the tracheal mucosa. Autophagy may alleviate tracheal fibrosis through up-regulating its expression level and play a protective role.

An enzyme-linked immunosorbent assay for detection of pyrene and related polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) can form DNA-binding compounds that show genotoxicity and carcinogenicity. Pyrene, as a PAH, was covalently linked to carrier protein bovine serum albumin and ovalbumin. A monoclonal antibody (McAb) was produced that showed high cross-reactivity values with chrysene (169.73%), benzo[a]pyrene (693.34%), benzo[a]anthracene (16.36%), and indeno[1,2,3-cd]pyrene (40.96%) and showed no significant cross-reactivity values with other homologues (<0.1%). A competitive enzyme-linked immunosorbent assay (ELISA) was developed for detection of pyrene and some homologues in water samples. The detection limit of the assay was 65.08 pg ml(-1). The average recoveries of PAHs from tap water, lake water, and mineral water were 99.13, 99.74, and 99.19%, respectively, indicating that matrices of water samples do not interfere with the assay. The results demonstrated that the developed ELISA seems to be a potential method for monitoring of pyrene and some homologous PAHs in water samples.

Clinical manifestations and radiological features may contribute to the early diagnosis of radiation-induced sarcoma after breast cancer.

AIM: To describe the clinical manifestations and radiological features contributing to the early diagnosis of radiation-induced sarcoma (RIS) after radiotherapy for breast cancer. MATERIALS AND METHODS: This retrospective analysis included four typical cases of RIS diagnosed at Affiliated Hospital of Academy of Military Medical Sciences between 1980 and 2013. Patient and imaging characteristics, treatment modalities, and outcomes were extracted from patients' medical records. Two pathologists reviewed all histological slides. RESULTS: All four cases were misdiagnosed and treated for several months as cases of breast cancer relapse. CT using the bone-window setting and three-dimensional reconstructions clearly displayed bone tumours of RIS in three cases. Skin alterations were observed in all cases. At the time of RIS diagnosis, three patients were free of breast cancer. In one patient with bilateral breast cancer and lung metastasis, chemotherapy resulted in complete remission of the metastasis, but RIS progression. No RIS in this series responded to chemotherapy or endocrine therapy. CONCLUSIONS: Abnormalities appearing in the radiation field long after RT should alert clinicians to the potential development of RIS. Careful physical examination and follow-up imaging studies are necessary. The presence of skin alterations, bone tumours at CT or radiography, and poor response to anti-cancer drugs may contribute to the early detection of RIS. Biopsy should be performed immediately when RIS is suspected.

[Cloning and characterization of lactate dehydrogenase C4 from pika ochotona curzoniae].

Lactate dehydrogenase C4 (LDH-C4) is considered to be a good target protein for the development of contraceptive drugs. To develop contraceptive rodenticide against pika (Ochotona curzoniae) LDH-C4, the pika LDH-C gene was cloned and expressed in Escherichia coli. The recombinant protein was purified and characterized. The cDNA of pika LDH-C gene was cloned by RACE method. The cDNA was 1498 bp in length containing an ORF of 996 bp which encoded a polypeptide of 332 amino acids. The ORF of pika LDH-C was introduced in E. coli and expressed with no fusion tags added. The recombinant LDH-C4 protein was purified by heating, affinity chromatography and ion-exchange chromatography. The recombinant pika LDH-C4 was a tetramer with a molecular weight of approximately 140 kDa, and it had temperature-dependent catalytic activity, as it was thermally stable up to 60 degrees C. The optimal pH values in the forward and backward reactions were around 7.48 and 10.28, respectively. The apparent Michaelis constants for pyruvate and lactate were 51.2 +/- 3.8 and 8568.8 +/- 409 microM respectively. The inhibition constant for oxalic acid was 11.8 +/- 3.5 mM. This study laid a solid foundation for contraceptive rodenticide development against pika LDH-C4.

Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.

Promoter hypermethylation of cyclooxygenase-2 gene in esophageal squamous cell carcinoma.

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies including esophageal squamous cell carcinoma (ESCC). However, a subset of ESCC either do not express COX-2 or show low level of expression. It is well established that promoter methylation is a major mechanism that mediates transcriptional silencing of COX-2 in gastric and colorectal cancer, but the data on ESCC are very limited. In this study, we attempted to determine whether COX-2 expression was also regulated by promoter methylation in human ESCC cell lines. We examined the methylation status of the COX-2 promoter in five human ESCC cell lines (EC109, EC9706, KYSE 410, KYSE 150, TE-1) using bisulfite sequencing analysis. Western blot analysis was used to determine COX-2 expression. Quantitative real-time polymerase chain reaction was used to determine COX-2 mRNA level. Prostaglandin (PG) E(2) was detected by ELISA. The promoter was densely methylated in TE-1 and KYSE 150, which had a low level of COX-2 expression and less methylated in other three cell lines (EC109, EC9706, KYSE 410), with high level of COX-2 expression. Treatment with 5-aza-deoxycytidine (5-aza-DC), a DNA methyltransferase inhibitor, demethylated the promoter and upregulated COX-2 expression, as well as PGE(2) production in TE-1 and KYSE 150. However, no such effects were observed in EC109. COX-2 protein was negative, but mRNA was positive in TE-1. After treatment with 5-aza-DC, both COX-2 mRNA and protein level had increased. These findings suggest that the promoter methylation may be one of the mechanisms that regulate COX-2 expression in ESCC.

Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1.

PURPOSE: Hypoxia is an indispensable factor in the progression of metastasis. Hypoxia inducible factor-1α (HIF-1α), the core element in generating the hypoxia response, induces invasion and metastasis by promoting epithelial-mesenchymal transition (EMT). This study explored the underlying mechanism of hypoxia associated with the invasion and metastasis of gastric cancer (GC). METHODS: Six methods were employed to assess the function of the long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) including gene silencing, RT-PCR, the separation of nuclear and cytoplasmic fractions, scrape motility assay, transwell migration assay, and Western-blot. RESULTS: LncRNA PCGEM1 was overexpressed in GC cells and tissues, and was induced by hypoxia in GC cells. Additional experiments confirmed that the knockdown of PCGEM1 significantly repressed the invasion and metastasis of GC cells. SNAI1, a key transcription factor of EMT, was regulated by PCGEM1. Overexpression of SNAI1 rescued the inhibition of PCGEM1-knockdown during the invasion and metastasis of GC cells. In addition, PCGEM1 and SNAI1 jointly affected the biomarkers of EMT. CONCLUSION: Our findings indicated that PCGEM1 is a hypoxia-responsive lncRNA, and contributes to the invasion and metastasis of GC. The potential mechanism is attributed to the regulation of EMT by PCGEM1 and its influence on the expression of SNAI1.

Wurtzite CoO: a direct band gap oxide suitable for a photovoltaic absorber.

A direct band gap of 1.6 eV has been identified in wurtzite CoO thin films, which matches the required value to achieve a theoretically high conversion efficiency solar cell. Its p-type conduction has been determined and an intense sub-gap absorption between 0.7 and 1.1 eV has been observed.