Clinical features of children with post-primary tuberculosis / 中华儿科杂志

Objective: The aim of this study was to summarize the clinical and imaging characteristics of post-primary tuberculosis in children, so as to improve the early identification and diagnosis of post-primary tuberculosis. Methods: This was a retrospective study which enrolled children who were admitted to the Department No.2 of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University between January 2015 to December 2020 and with a diagnosis of post-primary tuberculosis. Results: A total of 30 patients were enrolled, including 10 males and 20 females. The age on admission were 13.0 (12.0, 13.3) years. Their common symptoms were cough and fever, there were 26 cases (87%) with cough and 23 cases (77%) with fever, but only 4 cases (13%) had other toxic symptoms (night sweat, weakness or weight loss) of tuberculosis other than fever. Blood examination showed that the white blood cell count was (10±3)×109/L, accompanied by elevated proportion of neutrophils (0.69±0.11) and increased level of C-reactive protein (31 (15,81) mg/L). The common radiographic findings of CT were nodular or mass shadow with cavitation (19 cases (63%)), consolidation (13 cases (43%)), bronchogenic spread (12 cases (40%)), hilar or mediastinal lymphadenopathy (5 cases (17%)) in this cohort. The affected locations included the right upper lobe (21 cases (70%)), the left lower lobe (17 cases (57%)) and the right lower lobe (15 cases (50%)). Acid-fast bacillus smears and mycobacterial cultures were attempted for all cases, resulting in 33% (10/30) with smear positivity and 50% (15/30) with culture positivity. Conclusions: Post-primary tuberculosis in children has no specific clinical manifestations. Imaging of chest CT is mainly manifested as nodular shadow with cavitation, consolidation or bronchogenic spread. Accurate identification of post-primary tuberculosis is crucial for preventing the spread and early treatment of tuberculosis.

Ultrasonographic features of adenoma of the nonpigmented ciliary epithelium / 中华眼底病杂志

Objective:To analyze the ultrasonographic features of adenoma of the nonpigmented ciliary epithelium (ANPCE).Methods:A retrospective series of case studies. From January 2014 to October 2021, 31 patients (31 eyes) with ANPCE (ANPCE group) were diagnosed in the eye center of Beijing Tongren Eye Center of Beijing Tongren Hospital, Capital Medical University, and 17 patients (17 eyes) with ciliary body melanoma (control group) diagnosed at the same time were selected as the control group. There was no significant difference in age ( t=-0.564) and sex composition ratio ( χ 2=0.182) between the two groups ( P=0.576, 0.670). All patients underwent ultrasound biomicroscopy to obtain the measurement parameters: tumor height, maximum basal diameter, maximum diameter, ratio of maximum diameter to basal diameter and ratio of maximum diameter to height; tumor location, shape, internal echogenicity intensity, echogenicity uniformity, degree of sound attenuation, invasion of iris, anterior displacement of the iris, lens subluxation were observed. The measurement parameters and observation indexes of the two groups were compared by independent sample t-test and χ 2 test. Receiver operating characteristic (ROC) curve was drawn, area under the ROC curve (AUC) was determined, and parameter indicators with differential diagnosis value were screened. Results:The maximum diameter, height, maximum basal diameter, ratio of the maximum diameter to the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumors in the ANPCE group and the control group were 5.64±0.98 mm, 4.24±0.59 mm, 3.66±0.71 mm, 1.58±0.34, 1.34±0.19 and 7.82±2.03 mm, 4.47±2.44 mm, 7.02±1.96 mm, 1.13±0.16, 2.09±1.06. The maximum diameter, the maximum basal diameter, and the ratio of the maximum diameter to the height of the tumor in the ANPCE group were all smaller than those of the control group, and the ratio of the maximum diameter to the maximum basal diameter was greater than that of the control group, and the differences were statistically significant ( t=-4.159,-6.808, -2.924, 6.257; P<0.05). The tumors in the ANPCE group were mainly spherical (87.1%, 27/31), with no significant acoustic attenuation (77.4%, 24/31), less invading the root iris (77.4%, 24/31), and the tumors were mostly located in the ciliary body coronal (74.2%, 23/31); tumors in the control group were mainly hemispherical (47.1%, 8/17) or spherical (47.1%, 8/17), with significant sound attenuation (76.5%, 13/17), most of the tumors invaded the iris (70.6%, 12/17), and the tumors were mostly located from the pars plana to the coronal (76.5%, 13/17). There were statistically significant differences in the position, shape, sound attenuation degree, and whether it invaded the iris between the two groups of eyes ( χ 2=15.132, 19.767, 13.118, 10.581; P<0.05). The results of ROC curve analysis showed that the ratio of the largest diameter to the largest base diameter, the degree of sound attenuation and the AUC of whether the iris was violated were higher, which were 0.881, 0.769, and 0.740, respectively. Conclusions:Ultrasound biomicroscopy is helpful in the diagnosis and differential diagnosis of ANPCE and ciliary body melanoma. The ratio of maximum diameter to maximum basal diameter, the degree of sound attenuation and whether it invades the root iris are important parameters to distinguish the two tumors.

Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies: A New Paradigm of "State-Target Medicine" / 中国结合医学杂志

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.

Water migration and kinetics of Arecae Semen during moistening process / 中国中药杂志

In this study, low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were employed to analyze the water distribution, status, and migration in the moistening process of Arecae Semen. Peleg model was adopted to study the water absorption kinetics of Arecae Semen moistened at different water temperatures(10, 30, and 50 ℃). The Arecae Semen samples soaked at different water temperatures all contained four water states: binding water T_(21), non-flowing water T_(22), free water T_(23), and unbound water T_(24). Non-flowing water had the largest increase in peak area during the moistening process, followed by free water. The peak areas of non-flowing water, free water, and total water were correlated with the water content(P<0.01). Therefore, LF-NMR can quickly and non-destructively predict the water content of Arecae Semen during moistening. The peak area of non-flowing water and the content of free water were correlated with the content of arecoline in the soaking solution(P<0.01), which indicated that the faster flow of non-flowing water and more free water corresponded to more arecoline dissolved. The MRI images showed that the water migration pathway varied at different soaking temperatures, and the moistening degree obtained by this means was consistent with that obtained based on traditional experience. The rate constant K_1 fitted by Peleg model decreased with the increase in water temperature, while the capacity constant K_2 showed an opposite trend. The Arrhenius equation fitting of K_1 with temperature showed that the activation energy of Arecae Semen in the moistening process was 32.98 kJ·mol~(-1). LF-NMR/MRI can be used to analyze the water status and content and determine the end moisturing point of Arecae Semen. Peleg model can accurately describe the water absorption properties of Arecae Semen in the moistening process. The findings of this study can guide the moistening optimization and mechanism research of other seed Chinese medicinal materials.

Development of comprehensive ability evaluation system for general practice management post in community health service institutions / 中华全科医师杂志

Objective:To develop a comprehensive ability evaluation system for general practice management post in community health service institutions.Methods:Based on the previous studies and literature search on competency of general practitioners in various clinical posts, the first draft of the comprehensive ability indicator system for general management posts was designed. From November 2019 to January 2020, the comprehensive ability indicator system, classification and scoring method and evaluation method for general management posts were determined through three rounds of Delphi consultation.Results:Seventeen experts with administrative management experiences were invited for consultation, including 3 directors in charge and 14 general practice managers. The response rate of valid questionnaires in the three rounds of consultation were all 17/17, the authority of experts were all>0.7, and the coordination coefficients of expert opinions were 0.142, 0.212, and 0.532 (all P<0.01). The 11 evaluation indexes of the comprehensive ability of community general management posts were: achievement orientation, initiative, interpersonal understanding, service consciousness, influence, organization, training others, teamwork, team leadership, professional skills and confidence. Methods suitable for evaluation the ability of psychological test indicators were achievement orientation, interpersonal understanding, service consciousness and self-confident;appropriate indicators for no-leader group discussion were initiation, influence, team work, team leadership;appropriate indicators for in-tray test ability were organized cognition, professional skills;and the appropriate indicator for the ability of the structured interview was training others. Conclusions:The comprehensive ability evaluation system for community general management posts established in this study is scientific and practical, which may provide objective standard basis for the ability evaluation of community health management talents.

Analysis of ultrasonic features of melanocytoma of optic disc / 中华超声影像学杂志

Objective:To investigate the ultrasonic features, contrast-enhanced ultrasound findings and long-term follow-up results of melanocytoma of the optic disc(MCOD).Methods:The data of 35 patients (35 eyes, 35 lesions) diagnosed with MCOD in Beijing Tongren Ophthalmic Center, Beijing Tongren Hospital from September 2012 to October 2020 were retrospectively analyzed. The B-mode ultrasonography and color Doppler flow imaging (CDFI) were performed on them. The size, morphology, internal echo and secondary changes of the lesions were analyzed. Contrast-enhanced ultrasound was performed on 13 patients. At the same time, 9 patients were followed up for long-term observation.Results:Six lesions (17.1%) showed hemispherical high echo, and 29 lesions (82.9%) showed limited uplift high echo. The largest base diameter of the lesions was (4.0±0.8)mm, average height was(1.9±0.4)mm. Internal echo characteristics: 8 lesions (22.9%) showed uniform echo and 27 lesions (77.1%) showed uneven echo.Lesion boundary: 35 lesions (100%) showed clear lesion boundary. Fifheen lesions (42.9%) showed secondary vitreous opacity. CDFI: blood flow signals could be detected inside the lesions in 19 lesions(54.3%), and not in 16 lesions(45.7%). Contrast-enhanced ultrasound showed 11 of the 13 lesions (84.6%) were completely filled with contrast agent.Conclusions:MCOD has certain ultrasonographic characteristics, which can provide a reliable basis for clinical diagnosis and differential diagnosis. There is no significant change in tumor size after long-term follow-up.

Perfusion characteristics analysis of contrast-enhanced ultrasound in choroidal metastasis and choroidal hemangioma / 中华超声影像学杂志

Objective:To analyze the perfusion characteristics of choroidal metastasis using contrast-enhanced ultrasound, and compare with choroidal hemangioma.Methods:This was a retrospective study.From January 2016 to February 2018 in Beijing Tongren Hospital, a total of 21 eyes from 21 patients who were clinically diagnosed as choroidal metastasis were included as the choroidal metastasis group and 46 eyes from 46 patients who were diagnosed as choroidal hemangioma during the same period were included as the choroidal hemangioma group. All patients underwent contrast-enhanced ultrasound examination, and Sonoliver was used to obtain the data on quantitative parameters of the tumor and the adjacent normal orbital tissues, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (mTT). The quantitative parameters between choroidal metastasis and normal orbital tissues were compared. And the quantitative parameters between choroidal metastasis and choroidal hemangioma were compared. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance.Results:The IMAX of choroidal metastasis was significantly higher than that of normal orbital tissues, while RT, TTP and mTT were significantly shorter than these of normal orbital tissues (all P<0.01). The IMAX of choroidal metastasis was lower than that of choroidal hemangioma, and RT, TTP and mTT were shorter than choroidal hemangioma (all P<0.01). The ROC curve analysis showed that area under curves of the IMAX, RT, TTP and mTT were 0.775 (95% CI=0.666-0.884), 0.970 (95% CI=0.896-0.996), 0.729 (95% CI=0.607-0.831) and 0.992 (95% CI=0.931-1.000) respectively. The sensitivities were 71.7%, 95.7%, 76.1% and 95.7%, and the specificities were 85.7%, 90.5%, 66.7% and 95.2%, respectively. Conclusions:Contrast-enhanced ultrasound can reflect the differences in perfusion characteristics between choroidal metastasis and choroidal hemangioma. RT and mTT are useful parameters in differential diagnosis between the two types of tumors.

The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020) / 中华消化外科杂志

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Tumor lysis syndrome in multiple myeloma treated by daratumumab combined with chemotherapy: report of two cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical safety of daratumumab (DARA) in patients with relapsed/refractory multiple myeloma (MM).Methods:The diagnosis and treatment process of 2 cases of relapsed/refractory MM treated in Huadong Hospital of Fudan University in 2020 were retrospectively analyzed, the related laboratory indicators indexes after using DARA were analyzed, and the related literature was reviewed.Results:After using DARA, the 2 patients rapidly developed tumor lysis syndrome (TLS) such as high potassium, high phosphorus, high uric acid, low calcium and kidney damage, which eventually led to the death of patients.Conclusions:Patients with high tumor load treated by DARA are prone to TLS, which is often life-threatening. Clinicians should be alert to the occurrence of such events.

Application of comprehensive capacity assessment system based on post competence in competitive recruitment of family doctors / 中华全科医师杂志

This study is to evaluate the application of the comprehensive capacity assessment system based on post competence in competitive recruitment of family doctors. Thirty five general practitioners participating in the family doctor post competition in 2019—2020 were graded and ranked by both the post competition method and the comprehensive capacity assessment system of family doctors. The top 32 candidates in terms of total scores were selected as the successful candidates for the family doctor job competition. Kappa test was used to assess the consistency of competition results between the two methods. Among 32 candidates who were qualified according to the 2019—2020 family doctors post competition method, 31 (96.9%) were also qualified for the family doctor′s comprehensive capacity assessment system ( Kappa=0.635, P<0.01). The results indicate that the comprehensive capacity assessment system for family doctors based on post competency is rational and objective, and can be used for competitive recruitment of family doctors in community health service center.

The effect of enhanced external counterpulsation on heart failure with preserved ejection fraction in the elderly / 中华老年医学杂志

Objective:To investigate the effect of enhanced external counterpulsation(EECP)on heart failure with preserved ejection fraction(HFpEF)and hemodynamics in elderly patients.Methods:Clinical data of 66 elderly HFpEF patients admitted to the enhanced external counterpulsation center of our hospital from January 2018 to December 2019 were retrospectively analyzed.The primary assessment parameter was the six-minute walk distance, and the secondary parameters included the Minnesota Living with Heart Failure Questionnaire(MLHFQ). Noninvasive hemodynamic parameters including the cardiac index(CI), stroke volume(SV), isovolumic relaxation period(A2-mitral valve opening, A2-O), pulmonary capillary wedge pressure(PCWP)and total peripheral resistance(TPR)were monitored and mean arterial blood pressure(MAP)was calculated.Results:After EECP treatment, the six-minute walk distance increased(372±87 m vs.341±85 m, P<0.05), the score of MLHFQ decreased(47.0±16.0 vs.50.0±17.0, P<0.05), CI increased(2.8±0.7)L·min -1·m -2vs.(2.6±0.6)L·min -1·m -2( P<0.05), SV, PCWP and A2-O did not show significant change(73.3±16.4 ml vs.71.5±17.1 ml, 10.0±3.3 mmHg vs.11.0±3.6 mmHg, 1 mmHg=0.133 kPa, 98.0±29.5 ms vs.91.0±29.1 ms, P>0.05), TPR decreased(1 719.0±427.0 DS/cm 5vs.1 821.0±508.0 DS/cm 5, P<0.05), and there was no significant change in MAP(96.9±10.7 mmHg vs.98.8±13.1 mmHg, P>0.05), compared with pre-EECP treatment levels.Compared with patients without hypertension, MAP decreased in patients with hypertension(14 cases), when stratified by the initial MAP( P<0.05). Conclusions:For elderly patients with HFpEF, EECP can increase the six-minute walk distance, improve the quality of life and hemodynamic parameters, and is a safe adjuvant treatment.

Analysis of ultrasonic diagnostic features of juxtapapillary capillary hemangioma / 中华超声影像学杂志

Objective:To discuss the characteristics of ultrasound diagnosis of optic disc capillary hemangioma.Methods:The study analyzed retrospectively 7 cases of optic disc capillary hemangioma diagnosed in the Beijing Tongren Hospital from 2015 to 2018. The size, morphology, internal echo, and secondary changes of the lesion were analyzed during ultrasound examination.Color Doppler flow imaging was used to check the blood flow in the lesion.Results:Pre-optic disc occupying lesions could be detected in the ultrasound images of the 7 cases. Lesion size: average base diameters (5.39±1.90)mm×(4.79±1.28)mm, average height (3.61±1.37)mm. Lesion morphology: 5 cases were round, and 2 cases were irregular. Echo within the lesion: 3 cases had medium echo inside the lesion, and 4 cases had high echo inside the lesion. Internal echo characteristics: 5 cases had uniform echo, and 2 cases had uneven echo. Secondary changes: 6 cases had secondary retinal detachment and vitreous opacity, and 1 cases was accompanied by retinal hemangioma in other parts. In all cases, blood flow signals could be detected inside the space-occupying lesions, which were in the form of branches, stripes or spots, and the blood flow spectrum showed a parallel spectrum of arteries and veins.Conclusions:Ultrasound examination of optic disc capillary hemangioma has certain characteristics, which can provide a valuable follow-up basis for clinical diagnosis.

Advances on immune-related adverse events associated with immune checkpoint inhibitors / 医学前沿

Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

Construction and verification of RNA interfering lentiviral vector targeting Suv39h1 gene / 中国职业医学

OBJECTIVE: To construct the RNA interference(RNAi) lentiviral vector of suppressor of variegation 3-9 homolog 1(Suv39 h1) and verify its interfering efficiency by transfecting it to the bone marrow-derived mesenchymal stem cells(BMSCs). METHODS: The oligonucleotides of RNA plasmid were designed and synthesized according to the gene sequence of Suv39 h1 and short hairpin RNA design principles. Three kinds of LV-Suv39 h1-RNAi recombinant plasmids with different lentivirus knockdown targets(KD1, KD2 and KD3) were constructed. After identification by restriction analysis and sequencing, the packaged lentivirus vectors with the three kinds of Suv39 h1 gene were transfected into rat BMSCs at logarithmic growth stage, and were named KD1, KD2 and KD3 transfection groups. The control group was transfected with the negative control virus. After 72 hours transfection, the transfection efficiency was evaluated, and the relative mRNA levels of Suv39 h1 were determined by quantitative real-time polymerase chain reaction(qPCR). RESULTS: Sequencing analysis demonstrated that three kinds of LV-Suv39 h1-RNAi recombinant plasmids were constructed correctly. The results of transfection efficiency evaluation showed that more than 80.00% green fluorescence was expressed in the BMSCs transfected with the three lentiviral vectors with a multiplicity of infection of 20. These results indicated that lentivirus was successfully constructed and transfection efficiency was high. The results of qPCR showed that the relative expression of Suv39 h1 mRNA in BMSCs of KD1, KD2 and KD3 transfection groups was lower than that in the control group(all P<0.05), and the relative expression of Suv39 h1 mRNA in KD1 and KD3 transfection groups was lower than that in KD2 transfection group(both P<0.05). However, there was no significant difference in the relative expression of Suv39 h1 mRNA between KD1 and KD3 transfection groups(P>0.05). CONCLUSION: The constructed lentiviral vector with low expression of Suv39 h1 was constructed successfully. This vector can be expressed in rat BMSCs, which lays a foundation to study the effect of Suv39 h1 gene in acute myeloid leukemia.

Immediate and lasting effects of enhanced external counterpulsation on blood pressure in elderly patients with hypertension / 中华老年医学杂志

Objective:To investigate the immediate and lasting effects of enhanced external counterpulsation(EECP)on blood pressure in elderly patients with hypertension.Methods:In this real-world prospective non-randomized controlled study, the elderly hypertensive patients who were newly diagnosed as hypertension or had poor blood pressure control in the Geriatrics Department of Shandong University Qilu Hospital from May 2019 to December 2019, were enrolled as EECP group, and those with systolic blood pressure(SBP)≥180mmHg(1mmHg=0.133 kPa)or had contraindications for EECP treatment were excluded from EECP group(28 cases). Based on the 1∶1 ratio being consistent with the tendency score-matching method, patients' blood pressure was matched at 3 d before the start of the EECP treatment course, with other matched data of baseline data, coexisting disease, cardiovascular medication were choosed as control group(n=28). The EECP group received an additional 36 hours of EECP treatment(6 times/week, 1 hour/time)including lifestyle improvement and anti-hypertensive drugs.The patient's supine blood pressure was collected 3 minutes before each EECP treatment(baseline), 30 minutes during treatment, and 3 minutes after treatment.In the EECP group, family self-measured blood pressure was collected 3 days before the start of the 6-week treatment course(0w), the 6th week(6w)of the treatment course, and the 2nd week(+ 2w), 4th week(+ 4w)and 12th week(+ 12w)after the end of the treatment course, respectively.And the data of control group were collected at the same time point mentioned above.Results:Compared with baseline, the average immediate SBP of elderly hypertensive patients at the 30th minute of EECP treatment was decreased by(5.5±13.6)mmHg( P<0.001), and the average immediate diabolic blood pressure(DBP)was decreased by(1.1±7.5)mmHg( P<0.001). When the baseline SBP was between 160 and 169 mmHg, the probability of a further increase in SBP during treatment was 2.2%(2/89 cases), and when the baseline SBP was between 170 and 179 mmHg, the probability of a further increase in SBP during treatment was 0%(0/57). At 6 weeks, the decrease in SBP was significantly greater in the EECP group than in the control group[(-17.0±8.7)mmHg vs.(-10.5±7.3)mmHg, P<0.01], and the difference continued to + 2w[(-15.5±6.6)mmHg vs.(-10.6±2.5)mmHg, P<0.01]and + 4w[(-13.3±5.4)mmHg vs.(-10.7±2.1)mmHg, P<0.05]. At + 12w, the blood pressure drop was still greater in EECP group than in the control group, but it did not achieve statistically significant differences.Smoking history, history of diabetes, family history of hypertension, and improvement of comorbidities were the key factors that affect the continuous anti-hypertensive effect of EECP. Conclusions:EECP treatment has an immediate effect on lowering blood pressure in elderly hypertensive patients.A 6-week course of EECP treatment has a sustained effect on lowering blood pressure, and the effect can last from 4 to 12 weeks after the end of the course of treatment.

Advances in immunotherapy for neuroendocrine neoplasms / 中华胃肠外科杂志

Neuroendocrine neoplasms (NEN) is a rare and heterogeneous tumor. Different pathologic morphology, differentiation, grade and clinical stages of the tumors had various treatment and prognosis. Patients with recurrent or metastatic NEN have limited treatment options and poor prognosis. In recent years, PD-1 pathway blockade has become integral components of disease management for many cancers. Immunotherapy is being explored in NEN. Studies have shown that the efficacy of immune monotherapy in NEN is limited, and it can be considered for selected patients. Biomarkers for predicting efficacy of immunotherapy include PD-L1 expression, TMB-H, MSI-H/dMMR, etc. Combined regimens of anti-CTLA-4 and anti-PD-1/PD-L1 inhibitors, and immune checkpoint inhibitor combined with anti-angiogenic drugs or chemotherapy are promising in patients with NEN, and it is worthwhile to further explore of the responding populations.

The value of color Doppler ultrasound in the detection of macular diseases in age-related cataract patients / 中华眼底病杂志

Objective To observe the application value with color Doppler flow imaging (CDFI) in the detection ofmacular diseases in senile cataract.Methods A cross-sectional descriptive study.From December 1 to December 30,2017,720 senile cataract patients (1380 eyes) diagnosed in Beijing Tongren Eye Center were included in this study.There were 330 males (629 eyes) and 390 females (751 eyes),with the mean age of 70.35 ± 19.05 years.There were 716 right eyes and 664 left eyes,with the visual acuity 0.05-0.8.The fundus of all the patients can be observed.All patients were examined by OCT using Cirrus HD-Model 5000 produced by German Carl Zeiss company and CDFI using MyLab90 color Doppler ultrasound system produced by ESAOTE S.P.A.Comparing the detection rate of macular lesions between the two methods by using X2 test.Using statistical methods to evaluate diagnostic tests,a crosstabulation was made to compare the consistency of frequency-domain OCT and CDFI in the diagnosis of macular lesions.Logistic regression analysis of correlation between detection of CDFI macular lesions and central foveal thickness (CFT),average thickness (AT),with or without macular anterior membrane,retinal folds,retinal cystoid edema,hard exudation,macular hole or lamellar macular hole,superficial detachment of neuroepithelium,detachment of pigment epithelium,vitreous macular traction.Results Two hundreds and thirty-nine eyes (17.3％) showed macular disease by OCT,and 161 eyes (11.7％) showed the abnormal echo in the macular region by CDFI.The detection rate of the macular disease between two methods were statistically significant (χ2=851.661,P＜ 0.001),however,the consistency was well (r=0.766,P=0.000).Logistic analysis showed that the detection rate of macular lesions was related to retinal folds,cysts in retina and CFT (r=1.396,1.041,0.12;P＜0.01).Conclusion CDFI can effectively detect macular lesions that affect the visual prognosis of senile cataract patients.

Agreement of biometry parameters measured by IOLMaster 700 and Pentacam AXL in cataract eyes / 中华实验眼科杂志

Objective:To compare the agreement of biometric parameters measured by a new swept-source optical coherence tomography IOLMaster 700 and a new Scheimpflug imaging combined with partial coherence interferometry biometer Pentacam AXL in cataractous eyes.Methods:A cross-sectional study was performed.A total of 146 eyes from 76 cataract patients were enrolled in Beijing Tongren Eye Center from 2 to 11 in January 2018, including 69 eyes in 36 males and 77 eyes in 40 females, the age ranged from 35 to 88 years, the mean age was (64.52±11.36) years.Axial length (AL), mean keratometry (Km), anterior chamber depth (ACD), central corneal thickness (CCT) and white-to-white (WTW) were measured with IOLMaster 700 and Pentacam AXL, respectively.The differences and correlations of the biometry parameters between the two devices were assessed.Bland-Altman method was used to evaluate the agreement of these parameters between the two devices and the 95% limits of agreement was calculated.This study adhered to the tenets of the Declaration of Helsinki and was approved by an Ethics Committee of Beijing Tongren Hospital (TRECKY2018-049).Results:The mean values of the AL measured by IOLMaster 700 and Pentacam AXL were (24.03±1.72)mm and (23.98±1.73)mm, Km were (44.04±1.71)D and (43.88±1.72)D, ACD were (3.24±0.47)mm and (3.28±0.47)mm, WTW were (11.82±0.51)mm and (11.49±0.49)mm, respectively.Compared with the values in Pentacam AXL, the AL, Km and WTW were larger while ACD was smaller in IOLMaster 700 with significant differences ( t=18.06, 8.94, 23.83, -15.36, all at P<0.01). The mean CCT values from the IOLMaster 700 and Pentacam AXL were (534.18±30.12)μm and (533.42±28.71)μm, respectively, with no significant difference ( t=1.04, P=0.30). The AL, Km, ACD, CCT and WTW from IOLMaster 700 were highly correlated with those from Pentacam AXL ( r=0.999, 0.992, 0.998, 0.956, 0.942; all at P<0.01). The Bland Altman analysis showed that the 95% limits of agreement of AL, Km, ACD, CCT and WTW were-0.02-0.11 mm, -0.27-0.59 D, -0.10-0.02 mm, -16.5-18.1 μm and 0.00-0.67 mm. Conclusions:IOLMaster 700 and Pentacam AXL have good agreements and narrow 95% limits of agreement in the measurements of AL, ACD, CCT, which can be clinically interchangeable.The 95% limits of agreement of WTW and Km are out of the clinically acceptable range, so the WTW and Km measured by the two devices are not interchangeable.

Research progress of relationship between peritoneal microenvironment and peritoneal metastasis of gastric cancer / 中华消化外科杂志

Peritoneal metastasis is one of the most frequent metastatic patterns of advanced gastric cancer, but the mechanism underlying remains unclear. The 'seed and soil’ theory is now well recognized for peritoneal metastasis of gastric cancer at present. The combination of various cells, extracellular matrix, and ascites components within the abdominal cavity provide a suitable microenvironment for the plantation, infiltra-tion, growth and metastasis of gastric cancer cells. Fully under-standing of peritoneal microenvironment will help to diagnose the peritoneal metastasis of gastric cancer and tumor recurrence, and provide theoretical basis for the development of drugs targeting peritoneal microenvironment. The authors review the main cell formation, ascites and immune microenvironment involved in the formation of the peritoneal microenvironment based on relevant literatures at home and abroad, and investigate the relationship between peritoneal microenvironment and peritoneal metastasis of gastric cancer.

Infrequent gene mutations of KRAS, NRAS and BRAF in colorectal cancer and their clinical significance: a report of 1 513 cases / 中华消化外科杂志

Objective:To investigate the infrequent gene mutations of KRAS, NRAS and BRAF in colorectal cancer and their clinical significance.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 1 513 patients with colorectal cancer who were admitted to the Peking University Cancer Hospital from December 2013 to November 2018 were collected. There were 921 males and 592 females, aged from 15 to 97 years, with an average age of 59 years. The genomic DNA of tumor tissue was extracted, and the mutation status of KRAS (exon 2, 3), NRAS (exon 2, 3) and BRAF (exon 15) was detected by the Sanger sequencing. Observation indicators: (1) mutation status of KRAS, NRAS and BRAF; (2) relationship of different mutation status of KRAS, NRAS and BRAF with clinicopathological characteristics; (3) infrequent mutation status of single gene and its clinicopathological characteristics; (4) simultaneous mutations of two genes and their clinicopathological characteristics. Count data were expressed by absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test.Results:(1) Mutation status of KRAS, NRAS and BRAF: the mutation rates of KRAS, NRAS and BRAF were 37.806%(572/1 513), 3.173%(48/1 513) and 5.486%(83/1 513) of the 1 513 patients with colorectal cancer, respectively. The mutation rates of exon 2 and exon 3 in KRAS were 35.889%(543/1 513) and 1.917%(29/1 513), respectively. The mutation rates of exon 2 and exon 3 in NRAS were 1.322%(20/1 513) and 1.851%(28/1 513), respectively. The mutation rate of exon 15 in BRAF was 5.486%(83/1 513). The mutation of KRAS mainly occurred in codon 12, 13 of exon 2 and codon 61 of exon 3, with a mutation rate of 27.759%(420/1 513), 7.733%(117/1 513), and 1.586%(24/1 513), respectively. Infrequent mutation in codon 14, 59, 60 of KRAS were found in 7 patients with colorectal cancer [0.463%(7/1 513)], including V14I mutation in 2 cases [0.132%(2/1 513)], A59T mutation in 2 cases [0.132%(2/1 513)], A59E mutation in 2 cases [0.132%(2/1 513)] and G60D mutation in 1 case [0.066%(1/1 513)]. The mutation of NRAS mainly occurred in codon 12, 13 of exon 2 and codon 61 of exon 3, including Q61K with a mutation rate of 0.925%(14/1 513), followed by G12D with a mutation rate of 0.727%(11/1 513). The mutation rates of Q61R, Q61H, Q61L, G13R, G12C, G12V, G12S, G13D, and G13C were relatively low. The mutation of BRAF mainly occurred in codon 600 of exon 15 as V600E mutation, with a mutation rate of 4.957%(75/1 513). Infrequent mutation in BRAF were found in 8 patients with colorectal cancer, with a mutation rate of 0.529%(8/1 513), including D594G mutation in 5 cases [0.330%(5/1 513)], D594H mutation in 1 case [0.066%(1/1 513)], S607T mutation in 1 case [0.066%(1/1 513)], and 599-600 codon insertion AGA in 1 case [0.066%(1/1 513)]. Of the 1 513 patients, 4 [0.264%(4/1 513)] had simultaneous mutations at codon 12 and 13 of KRAS, including 2 [0.132%(2/1 513)] with simultaneous mutations at G12V and G13D, 1 [0.066%(1/1 513)] with simultaneous mutations at G12D and G13A, and 1 [0.066%(1/1 513)] with simultaneous mutations at G12V and G13F. In addition, 1 patient [0.066%(1/1 513)] had simultaneous mutations at G13D of KRAS and G12S of NRAS, and 1 patient [0.066%(1/1 513)] had simultaneous mutations at G12C of KRAS and Q61H of NRAS. (2) Relationship of different mutation status of KRAS, NRAS and BRAF with clinicopathological characteristics: patients with different tumor location and tumor differentiation degree had significantly different KRAS mutation status ( χ2=25.317, 4.166, P<0.05); patients with different gender, tumor location, tumor differentiation degree, and lymph node metastasis had significantly different BRAF mutation status ( χ2= 11.290, 22.317, 38.035, 12.611, P<0.05). The proportion of Q61K mutation and Q61R mutation of NRAS in the patients with age of < 65 and ≥ 65 years was 12/18, 2/10 and 1/18, 5/10, respectively, showing significant differences between the two groups ( χ2=5.600, 7.542, P<0.05). (3) Infrequent mutation status of single gene and its clinicopathological characteristics: 15 of the 1 513 patients had single gene mutation. Of the 7 patients with infrequent mutations in codon 14, 59 and 60 of KRAS, 6 were males and 1 was female; 6 were < 65 years old and 1 was ≥ 65 years old; 3 had tumors located in the left colon, 3 in the right colon and 1 in the rectum; 6 had highly or moderately differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma; 6 were in stage Ⅳ and 1 was in stage Ⅱ of TNM staging; 6 had distant metastasis and 1 had no distant metastasis; 3 had lymph node metastasis and 4 had no lymph node metastasis; there was no postoperative recurrence. Of the 8 patients with infrequent gene mutation of BRAF, 4 were males and 4 were females; 4 were < 65 years old and 4 were ≥ 65 years old; 5 had tumors located in the left colon, 1 in the right colon and 2 in the rectum; 7 had moderately differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma; 5 were in stage Ⅳ, 2 in stage Ⅲ, and 1 in stage Ⅱ of TNM staging; 6 had distant metastasis and 2 had no distant metastasis; 3 had lymph node metastasis and 5 had no lymph node metastasis; 1 had postoperative recurrence. (4) Simultaneous mutations of two genes and their clinicopathological characteristics: 6 of the 1 513 patients had simultaneous mutations of two genes. Of 6 patients with simultaneous mutations of two genes, 5 were males and 1 was female; 2 were < 65 years old and 4 were ≥ 65 years old; 1 had tumor located in the left colon, 4 in the right colon and 1 in the rectum; 5 had highly or moderately differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma; 5 were in stage Ⅳ and 1 was in stage Ⅱ of TNM staging; 4 had distant metastasis and 2 had no distant metastasis; 3 had lymph node metastasis and 3 had no lymph node metastasis; 1 had postoperative recurrence. Conclusions:The infrequent mutations of KRAS and BRAF in colorectal cancer often occur in the rare codon region and mainly are point mutations. Different mutations of KRAS, NRAS and BRAF are related to clinicopathological features, which provide an important basis for treatment of colorectal cancer.