Objective To understand how warfarin inhibition is hindered by the vitamin K epoxide reductase(VKORC1)resistant mutations.Methods An electrophoretic mobility assay was conducted based on the principle that binding with warfarin resulted in changes in VKORC1 electrophoretic mobility.The activity of VKORC1 and the half maximal inhibitory concentration(ICs0)of warfarin inhibiting VKORC1 were detected by ELISA.These experiments evaluated the binding ability of VKORC1 resistant mutants to warfarin.Results With warfarin bound,VKORC1 was protected from N-ethylmaleimide(NEM)modification and showed increased electrophoretic mobility,which was dependent on an unmodified cysteine on the flexible transmembrane helix 1(TM1)of VKORC1.In-creasing the warfarin concentration could shift more VKORC1 towards the species with the fast mobility.Compared to the wildtype VKORC1,the fast mobility fraction became less or disappeared in warfarin-resistant mutants,indi-cating weakened binding of warfarin.In addition,VKORC1 mutants with the weaker electrophoretic mobility shift indicated the stronger warfarin resistant.Conclusion Weakened warfarin binding is the primary cause of warfarin resistance.

ObjectiveTo analyze the fertility characteristics of the registered population in a neighborhood in Jing’an District， Shanghai from 2013 to 2022， and to provide a reference for population development planning and allocation of public health resources. MethodsData on newborns and puerperae registered in the neighborhood were collected through the Shanghai Birth Medical Information System and Public Security Department information system. Statistical analysis was conducted using Excel 2010， and the Joinpoint regression model was used to describe the changes. ResultsFrom 2013 to 2022， the crude birth rate， general fertility rate， and total fertility rate showed a declining trend， with average annual percent change （AAPC） values of -7.62%， -6.99%， and -4.54%， respectively. The average age of first childbirth and the age of childbearing among women gradually increased， with AAPC values of 1.24% and 1.28%， respectively. In the past 10 years， the total number of newborns showed a downward trend， with an AAPC value of -6.15%. After the implementation of the two-child policy， the proportion of second children showed an increasing trend， with an AAPC value of 7.37%. ConclusionThe fertility level of the population in the neighborhood is declining. The two-child policy has not significantly improved fertility rates， and the age of childbearing in women continues to rise. Diverse measures are needed to encourage childbirths and promote healthy births.

Cervical lymph node metastasis in thyroid cancer is closely related to the disease recurrence and prognosis of patients. Accurate judgment of lymph node metastasis is vital for tumor stage and treatment in patients with thyroid cancer, which can effectively improve the prognosis of patients. However, preoperative detection of cervical lymph node metastasis is the key points and difficulties in individualized treatment of thyroid cancer. Currently, fine needle aspiration washout fluid thyroglobulin is often used to assess cervical lymph node metastasis of differentiated thyroid cancer preoperatively, and it has a higher diagnostic efficacy. The continuous exploration and application of tumor markers and emerging biomarkers have provided new perspectives for the preoperative diagnosis of lymph node metastasis in thyroid cancer. As a new non-invasive detection technique, liquid biopsy is convenient to obtain samples and has broad clinical application in early diagnosis of cervical lymph node metastasis of thyroid cancer. In addition, the analysis and application of liquid biopsy biomarkers will help the development of clinical diagnosis and treatment strategies, and provide the possibility of early precision therapy for thyroid cancer patients. This review summarizes current research surrounding the molecular markers related to cervical lymph node metastasis of thyroid cancer.

Objective:To investigate the global cognitive function and the function of specific cognitive domains in hypertensive patients at high risk of cardiovascular disease in China, and to explore the impact of cognition function on blood pressure control.Methods:This is a cross-sectional survey. Data were obtained from the ESPRIT study. Patients with a history of hypertension who participated in the ESPRIT study from September 2019 to July 2020 were selected. Mini-mental state examination (MMSE) was used to evaluate patients′ overall cognition and the function of each cognitive domain. According to the total MMSE score, patients were divided into the cognitive-intact group (MMSE total score=30 points), cognitive-declined group (MMSE total score<30 points, but did not reach the dementia screening threshold) and cognitive-impaired group (MMSE total score reached the dementia screening threshold). A multivariable logistic regression model was used to explore the effects of cognitive function and MMSE score on blood pressure control. The years of education were removed from the adjustment variables for sensitivity analysis. The interaction effect modeling of stratified variables and exposed variables was used for hierarchical analysis.Results:A total of 10 834 patients with hypertension at high risk of cardiovascular disease were enrolled, aged 65 (60, 69) years and 4 476 (41.3%) patients were female. There were 989 patients in cognitive-intact group, 8 676 patients in cognitive-declined group and 1 169 patients in cognitive-impaired group. The MMSE score of all included patients was (25.6±3.8) points. In the overall study population, 10.8% (1 169/10 834) of hypertensive patients had cognitive impairment, with an MMSE total score of (18.6±4.1) points. The cognitive domains with obvious impairment were recall memory (-80%), visuospatial function (-64%), attention and computation (-60%); 80.1% (8 676/10 834) of hypertensive patients did not meet the criteria for cognitive dysfunction, but had cognitive decline, and the cognitive domains with significant impairment were recall memory (-51%) and visuospatial structure (-23%). Multivariate logistic regression analysis showed that cognitive dysfunction ( OR=0.88, 95% CI: 0.72-1.08, P=0.212) and cognitive decline ( OR=0.96, 95% CI: 0.83-1.12, P=0.629) was not correlated with blood pressure control. MMSE total score and scores in each cognitive domain were not correlated with blood pressure control ( P>0.05). Sensitivity analysis showed that cognitive function was not related to blood pressure control (all P>0.05). Stratified analysis according to different frequency of medication showed that cognitive function and MMSE score were not correlated with blood pressure control ( P>0.05). Conclusion:One in ten hypertensive patients who were at high risk of cardiovascular disease have comorbid cognitive impairment. In patients with high risk of cardiovascular disease, the most affected cognitive domains were recall memory, visuospatial function, attention and calculation. Part of hypertensive patients have not reached the level of cognitive dysfunction, but have begun to show cognitive decline. Cognitive function is not an independent influencing factor on blood pressure control.

Dry eye disease (DED) is a common ocular surface disease with significant impact on vision and quality of life.Early anti-inflammatory therapy with topical glucocorticoids and/or cyclosporine A (CsA) is recommended by the Tear Film & Ocular Surface Society Dry Eye Workshop (TFOS DEWS) Ⅱ report.Currently, there is no clear guidance on several aspects of the use of glucocorticoids and CsA in the management of DED, such as when and how to start therapy.Therefore, a European panel of dry eye experts developed a consensus through a questionnaire covering disease and progression, patient management, efficacy, safety and tolerability of CsA, patient education and criteria that are easy to apply in the clinic, and proposed specific treatment protocols for glucocorticoids and CsA in the treatment of DED.China has just started anti-inflammatory therapy for DED with little information to guide clinical practice.Hence, combining the consensus and relevant literature, this article interprets the role of inflammation in the development of DED, the inflammatory manifestations of DED and the anti-inflammatory therapy to guide the ophthalmologists in clinical practice.

Objective:To compare the safety and efficacy of high-dose- rate interstitial brachytherapy and particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases in the field after external radiotherapy.Methods:Clinical data of 42 patients with residual or newly metastatic pelvic lymph nodes after radiotherapy at Cangzhou Integrated Traditional Chinese and Western Medicine Hospital who met the inclusion criteria from January 2017 to April 2020 were retrospectively analyzed. Among them, 12 patients were male and 30 females, aged 39-82 years, (61.6±9.64) years on average. According to the treatment method, all patients were divided into the high-dose-rate interstitial brachytherapy group ( n=18) and particle implantation radiotherapy group ( n=24). During 3-year follow-up, the local control rate (LCR), incidence of complications and overall survival (OS) were compared between two groups. Age and operation time conforming to normal distribution were analyzed by t-test. The remaining indexes were analyzed by the Chi-square test or Fisher's exact test. The OS and LCR were calculated by Kaplan-Meier method. Results:There was no significant difference in baseline data between two groups (all P>0.05). The operation time in the high-dose- rate interstitial brachytherapy group was longer than that in the particle implantation radiotherapy group [(66.39±11.07) : (45.75±9.19) min, P<0.001]. During subsequent follow-up, there was no significant difference in the LCR between two groups (1-year LCR 88.9% vs. 87.5%, P=0.927; 2-year LCR 72.2% vs. 62.5%, P=0.874). There was no significant difference in the median OS between two groups (31.6 vs. 29.8 months, P=0.798). There was no significant difference in the incidence of early complications between two groups [ (4/18) vs. 5/24 (20.8%), P=1.000]. No late complications observed. Conclusion:High-dose- rate interstitial brachytherapy yields equivalent efficacy and safety to particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases.

Objective:To explore the effect of identifying pelvic lymph nodes by different injection of indocyanine green (ICG) during fluorescent laparoscopic radical cystectomy.Methods:The data of 54 male bladder cancer patients admitted to the First Hospital of Shanxi Medical University from September 2021 to September 2022 were analyzed. Preoperative cystoscopic biopsy all revealed a pathological diagnosis of urothelial carcinoma. All patients underwent fluorescent laparoscopic radical cystectomy plus pelvic lymph node dissection.They were divided into 3 groups according to the annotated route: 6 in the medial malleolus injection group, 68(61, 73) years; 4 in the perineal injection group, 67(59, 74) years; 44 in the medial malleolus and perineum, 64(45, 78) in the combined injection group. Under general anesthesia, patients were placed in the supine position with 0.3 to 0.5 ml of subcutaneous ICG solution (2.5 mg/ml) injected from 1.0 to 1.5 h before surgery. In the medial malleolus injection group, 0.3 to 0.5 ml (0.75 mg/place) was injected at 2 cm above the medial malleolus and 0.3 to 0.5 ml (0.75 mg/place) at two symmetrical sites above the anus. Intraoperatively, 4K fluorescent laparoscopy was used to observe the color development of the injection site and lymphatic vessels in vitro, and then to observe the development of pelvic lymph nodes in vivo.Results:In 3 groups, inguinal lymph nodes were developed about 30 min after ICG injection, and 1 h later, the longest (4.5±0.3) h. The external iliac and common iliac lymph nodes, the obturatorius lymph nodes in the perineal injection group, and the inguinal, obturatorius, external iliac, internal, anterior sacral, and common iliac lymph nodes in the medial malleolar and perineal injection group. In this study, in 54 cases, the postoperative pathological examination confirmed that the removed fluorescently labeled tissue was lymph node tissue, and the lymph node detection rate was 100%. The postoperative stage was pT 2, 14, 32 pT 3 and 8 pT 4; 4 pNx, 44 pN 0, 5 pN 1and 1 pN 2. In the medial malleolar injection group, 2 patients staged pT 2, 3 stage pT 3, 1 stage pT 4; 1stage pNx stage, 4 stage pN 0 and 1 stage pN 1 stage. In the perineal injection group, 4 patients had postoperative pathological stage pT 3N 0; in the medial malleolar and perineal injection group, 12 pT 2, 25 and 7 pT 3; 3 pNx, 36 pN 0, 4 pN 1 and 1pN 2. Conclusions:ICG injection through the perineum and subcutaneous labeling of pelvic lymph nodes, and the simple malleolus or perineal injection can not completely develop the pelvic lymph nodes. The combined injection could fully develop the pelvic lymph nodes, which may accurately guide the operator to locate, identify and remove pelvic lymph nodes.

OBJECTIVE To explore the distribution of airborne pollen in Cangzhou,to analyze the correlation between pollen characteristics,meteorological factors and the rate of allergic rhinitis visits,and to provide a reference basis for the precise prevention and treatment of allergic rhinitis in Cangzhou.METHODS The gravity deposition method was applied to collect daily airborne pollen from the monitoring sites in Cangzhou from March to October 2022 and record the pollen species and quantities.We also collected information on allergic rhinitis patients who visited the ENT Department of Cangzhou Central Hospital during the same period and meteorological data(daily maximum temperature,minimum temperature,maximum relative humidity,maximum precipitation,and maximum wind speed at ground level)during the same period,and analyzed the relationship between the number of AR patients'visits,the amount of pollen,and the meteorological factors.RESULTS 1.A total of 229 pollen exposures were collected from March to October 2022,totaling 19 368 pollen grains,of which 18 750 grains of pollen could be identified in 19 families and 618 grains were difficult to identify the families.2.There were two peaks of pollen during the period,in April and September respectively.Spring pollen to tree-based category,to the pine family,willow willow family,Xylariaceae(ash)most often;summer pollen volume has declined,but still tree-based category;fall pollen to herbaceous category,to the Asteraceae Artemisia,mulberry,Gramineae most often.3.The pollen concentration in Cangzhou City was negatively correlated with maximum humidity,maximum precipitation,maximum temperature,and minimum temperature.Maximum wind speed at ground level was positively correlated with pollen concentration.4.Pollen concentration was positively correlated with the number of visits.The correlation analysis between daily medical visits from June to October and air pollen concentration showed a significant positive correlation,while the results from March to May showed no significant correlation.CONCLUSION The peak of airborne pollen dispersal in April and September in Cangzhou.Spring and summer pollen is dominated by tree species,and the dominant pollen is Pinaceae,Willow genus of Populus,and Xylariaceae(ash genus);fall pollen is dominated by herbaceous species,and the dominant pollen is Artemisia,Asteraceae,Mulberry,and Gramineae.Meteorological factors are important factors affecting pollen concentration.Within a certain range,the lower the maximum humidity,the lowest maximum precipitation,the lower the highest or the lowest temperature,the higher the pollen concentration,and the pollen concentration is more affected by the lowest temperature.There is a correlation between pollen concentration and the number of AR patients'visits from June to October,which can be used as an environmental early warning indicator of the prevalence of AR.

As one of the research directions of novel dietary adjuvant treatment for heart diseases, ketogenic diet has the advantages of improving risk factors, inhibiting ventricular remodeling, and protecting the heart. This paper reviews and summarizes the research achievements of the effect of ketogenic diet on heart diseases and cardiovascular risk factors, elaborates the heart-related mechanism from multiple perspectives, analyzes its positive impacts on reducing cardiovascular disease risk factors and treating heart-related diseases, and summarizes the adverse reactions and contraindications of ketogenic diet, so as to provide new ideas for the prevention and treatment of heart diseases.