Efficacy and prognosis comparison of first-line treatment with EGFR-TKI versus chemotherapy for non-small cell lung cancer patients harboring EGFR rare mutation / 肿瘤研究与临床

Objective:To investigate the therapeutic effect difference between first-line treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) and chemotherapy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) rare mutation.Methods:A retrospective case-control study was performed. Data of NSCLC patients with rare EGFR mutation who were treated in Shanxi Province Cancer Hospital from January 2013 to October 2019 were retrospectively analyzed. EGFR mutations in living tissues or blood were detected by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) before first-line treatment. According to first-line treatment methods,they were divided into EGFR-TKI treatment group and chemotherapy group. Objective remission rate (ORR) and disease control rate (DCR) of both groups were compared. Kaplan-Meier method was used to draw progression-free survival (PFS) and the overall survival (OS) curves. Log-rank test was used for comparison among groups. Single-factor and multi-factor Cox proportional risk models were used to analyze the influencing factors of PFS and OS.Results:A total of 169 patients with EGFR rare mutations were included, and the age [ M (IQR)] was 63 years (12 years); there were 96 cases (56.8%) < 65 years and 73 cases (43.2%) ≥65 years; 70 (41.4%)males and 99 (58.6%) females; 55 cases (32.5%) had EGFR G719X mutation,45 cases (26.6%) had L861Q mutation, 17 cases (10.1%) had S768I mutation, and 52 cases (30.8%) had complex mutation; 55 cases (32.5%) received the first-line chemotherapy and 114 cases (67.5%) received the first-line EGFR-TKI treatment. In the chemotherapy group, ORR was 36.4% (20/55) and DCR was 85.5% (47/55); in EGFR-TKI treatment group, ORR was 72.8% (83/114) and DCR was 90.4% (103/114). The ORR of EGFR-TKI treatment group was higher than that of chemotherapy group ( χ2 = 20.70, P = 0.001), and there was no statistically significant difference in DCR between two groups ( χ2 = 1.76, P = 0.184). Subgroup analysis showed that ORR in EGFR-TKI treatment group with G719X, L861Q and complex mutations was higher than that of the corresponding mutations in chemotherapy group, and the differences were statistically significant (all P < 0.05), while there were no significant differences in DCR among subgroups (all P > 0.05). The median PFS time was 9.7 months (95% CI: 6.0-13.4 months) and 3.8 months (95% CI: 3.1-7.1 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was a statistically significant difference in PFS between the two groups ( P < 0.001). The median OS time was 25.6 months (95% CI: 18.0-37.9 months) and 31.7 months (95% CI: 18.0-42.8 months), respectively in EGFR-TKI treatment group and chemotherapy group, and there was no statistically significant difference in OS between the two groups ( P = 0.231). Multivariate Cox regression analysis showed that brain metastasis [with vs. without: HR = 2.306, 95% CI: 1.452-3.661, P < 0.001] and the first-line treatment methods (EGFR-TKI vs. chemotherapy: HR = 0.457, 95% CI:0.317-0.658, P < 0.001) were independent influencing factors for PFS of NSCLC patients with EGFR rare mutation; brain metastasis (with vs. without: HR = 2.087, 95% CI: 1.102-3.953, P = 0.024; unknown vs. without: HR = 2.118,95% CI: 1.274-3.520, P = 0.004) were independent influencing factors for OS of NSCLC patients with EGFR rare mutation. Conclusions:Compared with the first-line chemotherapy, EGFR-TKI first-line treatment could improve objective remission and PFS of NSCLC patients with EGFR rare mutation, while no OS benefit is observed.

Mediating effect of mindfulness on the relations between fear of cancer recurrence and quality of life in patients with lung cancer / 现代临床护理

Objective To investigate the mediating effect of mindfulness on the relations between FCR and QOL.Methods A total of 240 lung cancer patients who were admitted to 3 hospitals in Shanxi Province,from January 2022 to January 2023,were enrolled in the study by convinient sampling.The fear of progression questionnaire-short form(FoP-Q-SF),mindfulness attention awareness scale(MAAS)in Chinese and the European Organisation for Research and Treatment for Cancer Quality of life questionnaire(EORTC QLQ)were employed in the cross-sectional survey.Multiple linear regression was used to analyse the association between FCR and QOL,and Bootstrap Model was adopted to analyse the mediating effect of mindfulness between FCR and QOL.Results A total of 240 questionnaires were distributed and 217 of them were retrieved,with an effective retrieval rate of 96.42%.FCR was found at a moderate level in all lung cancer patients,and it was negatively associated with the mindfulness and QOL(r=-0.348,P<0.01:r=-0.331,P<0.01).Bootstrap analysis revealed that the changes in mindfulness score acted as an intermediate variable between FCR and QOL,mediating 25.68%of the relationship.Conclusions FCR in lung cancer patients is negatively associated with QOL.This association may be explained by the reduction in mindfulness experienced by the patients.

Analysis of clinicopathological features and prognostic factors of breast cancer patients with different molecular subtypes / 肿瘤研究与临床

Objective:To explore the differences in clinicopathological features, survival status and prognostic influencing factors of breast cancer patients with different molecular subtypes, and to provide bases for the prevention and treatment of breast cancer.Methods:The clinicopathological data of new-onset female breast cancer patients hospitalized in Shanxi Province Cancer Hospital from January 2015 to December 2016 were retrospectively analyzed, and patients were followed up. The clinicopathological features of patients with different molecular subtypes were compared. The follow-up was performed until June 30, 2021. Kaplan-Meier method was used to analyze the survival of patients, and Cox proportional hazards model was used to analyze the factors affecting overall survival (OS) of patients with different molecular subtypes.Results:There were 272 (14.9%), 1 005 (55.2%), 277 (15.2%) and 268 (14.7%) patients with subtypes of Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative breast cancer (TNBC), respectively. The differences in the distribution of patients with age at diagnosis, age at menarche, menopausal status, age at menopause, pathological type, longest tumor diameter, T staging, N staging, histological grading, and TNM staging were statistically significant among the four groups (all P < 0.05). At a median follow-up of 60 months, the 5-year OS rates of Luminal A, Luminal B, HER2 overexpression and TNBC subtypes were 93.8%, 89.2%, 77.6% and 78.0%, respectively, and the difference was statistically significant ( χ2 = 58.76, P < 0.001). M staging was an independent influencing factor for OS in patients with Luminal A breast cancer ( HR = 16.789, 95% CI 4.972-56.690, P < 0.001); T staging ( HR = 2.721, 95% CI 1.715-4.319), N staging ( HR = 4.460, 95% CI 2.399-8.291) and M staging ( HR = 3.364, 95% CI 1.988-6.670) were independent influencing factors for OS in patients with Luminal B breast cancer (all P < 0.001); N staging ( HR = 4.428, 95% CI 1.836-10.677) and M staging ( HR = 13.489, 95% CI 6.043-30.107) were independent influencing factors for OS of patients with HER2 overexpression breast cancer (both P < 0.01); T staging ( HR = 3.052, 95% CI 1.575-5.915), N staging ( HR = 2.492, 95% CI 1.298-4.785) and M staging ( HR = 33.012, 95% CI 8.606-126.637) were independent influencing factors for OS of patients with TNBC (all P < 0.01). Conclusions:The clinicopathological features and prognostic influencing factors of breast cancer patients with different molecular subtypes are different, and the prognosis of HER2 overexpression and TNBC patients is poor. Clinicians should provide individualized treatment and follow-up programs for patients with different molecular subtypes of breast cancer.

Correlation of preoperative peripheral blood neutrophil-lymphocyte ratio and blood platelet-lymphocyte ratio and immune indexes with the prognosis of cervical cancer patients / 肿瘤研究与临床

Objective:To evaluate the value of preoperative peripheral blood neutrophil-lymphocyte ratio (NLR) and blood platelet-lymphocyte ratio (PLR) and immune indexes in the evaluation of the prognosis of cervical cancer patients.Methods:The clinical data of 283 patients with cervical cancer who underwent radical surgery in Shanxi Province Cancer Hospital from May 2017 to September 2018 were retrospectively analyzed, and 100 healthy people who underwent physical examination during the same period were collected as the healthy control group. Test results of blood cells and immune cells expressions of all subjects were collected. Peripheral blood NLR and PLR of cervical cancer patients, people in the healthy control group and cervical cancer patients with different pathological characteristics were compared. Kaplan-Meier method was used to make survival analysis and Cox regression risk model was used to analyze the factors influencing the prognosis of patients with cervical cancer.Results:The preoperative peripheral blood NLR and PLR in patients with cervical cancer was higher than that of the healthy control group (NLR: 2.53±1.35 vs. 2.00±1.21, t = 5.35, P < 0.001; PLR: 163±57 vs.144±38, t = 4.71, P = 0.006). Pathological results showed that there were no statistically significant differences in NLR and PLR in peripheral blood of cervical cancer patients with different pathological types, tumor diameter, vascular invasion, and nerve invasion (all P > 0.05), while there were statistically significant differences in NLR and PLR in peripheral blood of cervical cancer patients with different clinical staging and muscle wall invasion (all P < 0.05). When the proportions of the expression levels of preoperative CD3 positive cells, CD4 positive cells, CD8 positive cells, CD19 positive cells, CD56 positive cells, and CD127 positive cells were 60%-85%, 30%-40%, < 25%, 8%-15%, 15%-25% and < 5%, respectively, the overall survival of cervical cancer patients was the best. Univariate analysis showed that pathological type, clinical staging, vascular invasion, preoperative NLR, preoperative PLR,CD3 positive cells, CD4 positive cells, CD8 positive cells, CD19 positive cells, CD56 positive cells and CD127 positive cells were influencing factors of the overall survival of cervical cancer patients (all P < 0.05). Multivariate analysis showed that clinical staging, vascular invasion, preoperative NLR, preoperative PLR, and preoperative CD4 positive cells were independent influencing factors for the overall survival of cervical cancer patients (all P < 0.05). Conclusions:Preoperative high NLR and PLR in peripheral blood have a certain impact on the clinicopathological characteristics and poor prognosis of cervical cancer patients. When the immune cells in peripheral blood are in dynamic balance, the prognosis of cervical cancer patients is the best.

Study of 3D-printed multi-channel applicator in patients treated with brachytherapy after cervical cancer surgery / 中华放射肿瘤学杂志

Objective:To compare the dosimetric difference between 3D-printed multi-channel applicator and conventional vaginal single-channel applicator for brachytherapy, aiming to provide guidance for patients receiving brachytherapy after cervical cancer surgery.Methods:From January 2019 to November 2020, 25 cervical cancer patients complicated with VAIN Ⅲ receiving 192Ir high-dose-rate brachytherapy after cervical cancer surgery were selected. Each patient was located by CT scanning with 3D-printed multi-channel applicator and conventional vaginal single-channel applicator, and corresponding plan and evaluation were carried out. The dose volume histogram (DVH) was obtained by inverse dose optimization algorithm. The dosimetric differences of high-risk clinical target volume (HRCTV), bladder and rectum during brachytherapy were compared with those of source applicators. The optimal treatment plan was selected. Results:D 90%, D 100%, V 100% and V 150% of the plans designed by 3D-printed individual multi-channel applicator had no significant differences compared with those designed by conventional single-channel applicator (all P>0.05). The bladder and rectal D 2cm 3 designed by 3D-printed multi-channel applicator were significantly lower than those using conventional single-channel applicator, and the differences were statistically significant (both P<0.05). Conclusion:The multi-channel individual applicator target made by 3D-printing technology has good conformal property, properly protects the bladder and rectum and possesses treatment advantages over conventional single-channel applicator.

Clinical study of association between breast cancer and thyroid diseases / 肿瘤研究与临床

Objective:To investigate the association between breast cancer and thyroid diseases, and to provide evidence for the prevention and treatment of thyroid diseases in breast cancer patients.Methods:A total of 511 newly diagnosed breast cancer patients were recruited between March 2018 and August 2019 from Shanxi Province Cancer Hospital, and 303 age-matched newly diagnosed breast benign disease patients and 341 age-matched healthy controls were recruited during the same time-frame. Thyroid B-ultrasound and thyroid function test were performed in the three groups. By reviewing the medical records, the general and clinicopathological data of the patients were collected, and the differences in the prevalence of thyroid diseases among the three groups were compared. The changes of thyroid function in breast cancer patients before treatment, in the middle stage of chemotherapy and at the end of chemotherapy were compared.Results:Among breast cancer group, breast benign disease group and healthy control group, the differences in the prevalence rates of hypothyroidism [32.5% (166/511), 25.7% (78/303) and 21.7% (74/341)], thyroid nodules [50.7% (259/511), 43.2% (131/303) and 41.6% (142/341)] and Thyroid Imaging Reports and Data System(TI-RADS) grade 4 and above thyroid nodules [15.4% (40/259), 14.5% (19/131) and 4.9% (7/142)] were statistically significant (all P < 0.05). The abnormal rates of thyroid stimulating hormone (TSH) and free thyroxine (fT4) in breast cancer group were higher than those in breast benign disease group and healthy control group [34.1% (174/511) vs. 26.1% (79/303), 23.5% (80/341); 24.9% (127/511) vs. 8.6% (26/303), 3.2% (11/341)], and the differences were statistically significant (both P < 0.05). The levels of fT4, free three iodide thyroxine (fT3), thyroid immunoglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) in breast cancer patients before treatment, in the middle stage of chemotherapy and at the end of chemotherapy were statistically different (all P < 0.05). The abnormal rates of fT4, TgAb and TPOAb in the last chemotherapy cycle were lower than those before chemotherapy [11.5% (59/511) vs. 24.9% (127/511), 5.1% (26/511) vs. 17.4% (89/511), 11.9% (61/511) vs. 20.4% (104/511)] in breast cancer patients, and the differences were statistically significant (all P < 0.001). Conclusions:The breast cancer is associated with thyroid diseases. Clinicians should pay more attention to the changes of thyroid diseases and thyroid function during the treatment and in the follow-up process of breast cancer patients, so as to detect the thyroid diseases early and carry out standardized treatment.

Research progresses on the cognitive impairment of Duchenne muscular dystrophy / 中华实用儿科临床杂志

Duchenne muscular dystrophy(DMD) is an X-linked hereditary neuromuscular disorder caused by dystrophin gene mutation.About 1/3 of DMD patients have cognitive impairment.Early detection of cognitive impairment is essential for early diagnosis and the quality of life.This review summarized the recent progress in the clinical features, pathogenesis, brain structure changes, and cognitive impairment intervention of DMD.

Clinical efficacy analysis of peritoneal dialysis in end-stage renal disease with cirrhotic patients / 中华肾脏病杂志

Objective:To investigate the efficacy and safety of peritoneal dialysis (PD) in end-stage renal disease (ESRD) patients with liver cirrhosis (LC).Methods:Clinical data of PD patients receiving regular treatment followed up for≥6 months, and aged≥18 years in the Third Affiliated Hospital of Hebei Medical University Peritoneal Dialysis Center from January 1, 2013 to March 31, 2020 were retrospectively collected. The patients were divided into LC-PD group and non-LC-PD group according to whether they had LC or not. Propensity score matching (PSM) was used to match the LC-PD group and the non-LC-PD group with 1∶4 ratio. The baseline clinical data, dialysis adequacy, peritonitis and clinical outcomes between the two groups were compared. Kaplan-Meier survival curve and Log-rank test were used to compare the survival rate and technical survival rate between the two groups.Results:A total of 241 PD patients were included in this study. After PSM, 13 cases in LC-PD group and 52 cases in non-LC-PD group were included. Compared with non-LC-PD group, patients in LC-PD group had lower baseline urine volume ( Z=-3.546, P<0.001) and serum albumin ( Z=-2.609, P=0.009). At the follow-up of 3, 6, 12 and 24 months, total serum protein ( t=-3.319, P=0.002), serum albumin ( t=-4.019, P<0.001), triglyceride ( Z=-2.263, P=0.024), and serum phosphorus ( Z=-2.173, P=0.030) in the LC-PD group were lower than those in non-LC-PD group. During the follow-up period of 2 years, the patients in the LC-PD group had significantly higher serum albumin than baseline values ( χ2=16.901, P=0.001), and there was no statistically significant difference between the two groups ( χ2=0.155, P=0.694). The decline rate of residual kidney Kt/V in the LC-PD group was slower than that in the non-LC-PD group ( χ2=44.589, P<0.001). The incidence of peritonitis in LC-PD group was higher than that in the non-LC-PD group, with a statistically significant difference (0.59/patient-year vs 0.20/patient-year, Z=-2.135, P=0.033). The composition ratio of pathogenic bacteria in both groups was mainly gram-positive bacteria (10/25 vs 11/30) and proportion of Streptococcus in LC-PD group was higher than that in non-LC-PD group (4/10 vs 0/11, P=0.035). The proportion of Escherichia coli in the first peritonitis was higher than that in LC-PD group (4/9 vs 1/22, P=0.017). The Kaplan-Meier survival curve results showed no statistically significant difference in survival rate (Log-rank χ2=0.491, P=0.484) and technical survival rate (Log-rank χ2=0.408, P=0.523) between the two groups. Conclusions:PD is a safe and effective treatment mode for ESRD patients with LC, and the survival rate and technical survival rate are comparable to those patients without LC. The incidence of peritonitis in patients with LC-PD in our dialysis center is higher than that in the non-LC-PD patients, and gram-positive bacterial infections are the mainstay, suggesting that attention should be paid to strengthening patient management and training.

Safety pharmacological study of the compound of diphenhydramine hydrochloride and caffeine / 药学实践杂志

Objective To provide the reference resource for the safe clinical use of the compound of diphenhydramine hydrochloride and caffeine by observing its effects on the nervous system, cardiovascular system and respiratory system in experimental animals. Methods Single dose of the compound of diphenhydramine hydrochloride and caffeine was given to animals orally. The effects on climbing ability of mice and blood pressure, electrocardiogram, respiration rate and amplitude in beagle dogs were observed and recorded. Results With the dosage of the compound of diphenhydramine hydrochloride and caffeine (diphenhydramine hydrochloride / caffeine ratio is 1/2.4) at 51, 102, 204 mg/kg, there was no significant effect on the climbing ability in mice. With the dosages of 14.2, 28.3, 56.6 mg/kg for male Beagle dogs and 5.66, 14.2, 28.3 mg/kg for female Beagle dogs, no significant effects were observed in systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, ECG（P wave, R wave , T wave, QRS time, PR interval, QT interval）, respiratory rate and amplitude. Conclusion Under the experimental conditions, single oral dose of the compound of diphenhydramine hydrochloride and caffeine has no significant effect on the nervous system, cardiovascular system and respiratory system in experimental animals. Those results suggest that the compound of diphenhydramine hydrochloride and caffeine is a safe agent for clinical use.

Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients

Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. @*Methods@#We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. @*Results@#Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. @*Conclusions@#The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

Analysis of clinicopathological features and factors influencing the survival of young breast cancer patients / 肿瘤研究与临床

Objective:To explore the clinicopathological characteristics and factors influencing the survival of young breast cancer patients with diagnostic age below 35 years, and to provide the basis for the prevention and treatment of young breast cancer patients.Methods:Epidemiological and clinicopathological data of young female patients with newly diagnosed breast cancer from Shanxi Province Cancer Hospital between January 2015 and December 2016 were retrospectively analyzed. The data included age at diagnosis, reproductive history, history of abortion, menopausal status, and immunohistochemical results. Univariate and multivariate analysis were performed by using Cox regression model.Results:A total of 118 young breast cancer patients were collected, and the median age was 31 years old. Among them, the vast majority of 118 young breast cancer patients were invasive cancer (113 cases, accounting for 95.8%); there were 65 cases (55.1%) with tumor diameter ≤ 20 mm, 61 cases (51.7%) at N 0 stage, and 112 cases (94.9%) at M 0 stage. The positive rates of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) were 73.7% (87/118), 69.5% (82/118) and 28.8% (34/118), respectively. Luminal B breast cancer was the predominant molecular subtype, accounting for 55.1% (65/118). By the end of follow-up (median follow-up period of 60 months), the overall survival rate of young breast cancer patients was 78.8%. Multivariate analysis showed that TNM staging was an independent factor affecting overall survival in young breast cancer patients ( HR = 7.858, 95% CI 2.924-21.120, P < 0.001). Conclusions:Young breast cancer patients have unique clinicopathological features and TNM staging is an independent factor affecting the prognosis. Individualized treatment helps to improve the quality of life and prolong the survival time of patients.

Target-responsive subcellular catabolism analysis for early-stage antibody-drug conjugates screening and assessment

Events including antibody‒antigen affinity, internalization, trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody-drug conjugate (ADC) catabolism and hence the toxicity. Nevertheless, an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking. Considering the plethora of ADC candidates under development, we developed a target-responsive subcellular catabolism (TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest. We firstly applied TARSC to study the commercial T-DM1 and the biosimilar. We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences. Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further

Progress of rare epidermal growth factor receptor mutations in non-small cell lung cancer / 肿瘤研究与临床

With the development of biomolecular diagnostic technology and genetic analysis, it has been gradually discovered that some gene abnormalities can drive the occurrence and development of lung cancer. Among them, epidermal growth factor receptor (EGFR) is the most common mutant gene in non-small cell lung cancer (NSCLC). However, most of the current researches focus on the common mutations of EGFR, such as exon 19 deletion (19del) and exon 21 point mutation (L858R). There are few studies on rare EGFR mutations. This article reviews the progress of rare EGFR mutations in NSCLC.

Interobserver variation in the morphological evaluation of nuclear features of noninvasive follicular thyroid neoplasm with papillary like nuclear features / 中华内分泌代谢杂志

Objective:To evaluate the interobserver variation of pathologists in the morphological evaluation of non-invasive follicular thyroid neoplasm with papillary-like nuclear features(NIFTP).Methods:Nine pathologists from different regions in China were selected to evaluate the digital slides of 30 cases of NIFTP. Three score system was applied, including nuclear size and shape, membrane irregularity, and chromatin features. Individual histologic features were scored as either present(1)or absent(0). A total score of 0 or 1 was considered inadequate for the diagnosis of NIFTP and a total score of 2 or 3 was considered sufficient for the diagnosis of NIFTP.Results:Overall, 9 doctors had weak consistency in the interpretation of the 30 cases(Kappa value 0.081 4), in which the interpretation of the membrane irregularity had the best consistency(Kappa value 0.193 6)and the interpretation of nuclear size and shape revealed the worst consistency(Kappa value 0.102 2). The overall consistency of the evaluation from the 7 senior pathologists was better than that of all the pathologists(Kappa value 0.134 1), but it was still weak. The consistency of nuclear membrane irregularity(Kappa value 0.267 4)and nuclear chromatin features(Kappa value 0.257 3)was weak, but much better than that of nuclear size and shape(Kappa value 0.073 0). The interobserver consistency in our study was lower than that in Asian study generally. However, the judgement on membrane irregularity in our senior pathologists was better than that in Asian study.Conclusion:The interobserver variation on the evaluation of the nuclear features of NIFTP is probably due to the education level, working experience, personal understanding of the diagnostic criteria, the regional difference, and some uncertain reasons. There is overall a weak consistency in the interpretation of NIFTP by Chinese pathologists, and it is necessary to popularize the diagnostic criteria and specify the criteria in detail. It is important to exclude high-risk genetic mutation using immunohistochemical staining or molecular examination on those patients with morphology of NIFTP.

Clinical effects of Shendan-Huoxue capsule combined with etoposide soft capsules in the treatment of advanced ovarian carcinoma in elderly patients / 国际中医中药杂志

Objective To evaluate the clinical effects of Shendan-Huoxue capsule combined with etoposide soft capsule in the treatment of advanced ovarian cancer in the elderly patients. Methods A total of 94 elderly patients with ovarian cancer who met the inclusion criteria were divided into 2 groups using random number table method, 47 patients in each group. All patients were given conventional chemotherapy, the control group was given etoposide soft capsule on this basis, and the observation group was given Shendan-Huoxue capsule on the basis of the control group. Both groups were treated for 12 weeks and followed up for 2 years. Ovarian cancer specificity scale version 4 (FACT-OV4) was used to evaluate the life quality of the patients, flow cytometry was used to detect the level of CD3+, CD4+, CD8+, CD19+. Ovarian cancer was detected by CT, toxic and side effects during treatment were recorded, and clinical efficacy was evaluated. Results The total effective rate in the observation group was 87.2% (41/47), and that in the control group was 70.2% (33/47). The difference between the two groups was statistically significant (χ2=3.782, P=0.041). The 1-year survival rate was 87.2% (41/47) and 2-year survival rate was 61.7% (29/47) in the observation group, and 74.4% (35/47) and 53.2% (25/47) in the control group, respectively. The 1-year and 2-year survival rates of the two groups were statistically significant (χ2=4.109, 4.268 respectively, P=0.038, 0.036). The median total survival time in the observation group and the control group was 13.9 months (95% IC 12.4-16.2) and 10.3 months (95% IC 8.2-14.1), respectively. The median total survival time in the observation group was significantly longer than that in the control group (P<0.05). After treatment, scores of social/family status and functional status in the observation group were significantly higher than those in the control group (t values were 3.711 and 4.003, respectively, P<0.05), and scores of additional attention, physiological status and emotional status were significantly lower than those in the control group (t values were 4.335, 4.522 and 4.202, respectively, P<0.05). After treatment, the levels of CD3+, CD4+, CD8+, CD19+ in the observation group were all higher than those in the control group (t values were 7.217, 7.129, 7.434 and 6.521, respectively, P<0.01 or P<0.05). During the period of treatment , the incidence of skin rash, liver function injury, decreased white blood cell count, nausea and vomiting, peripheral neuropathy, diarrhea and abdominal pain in the observation group were significantly lower than those in the control group (χ2 values were 4.114, 4.782, 4.521, 3.911, 3.931, 3.821, P<0.05, respectively). Conclusions The Shendan-Huoxue capsule combined with etoposide soft capsule can improve the survival time of elderly patients with advanced ovarian cancer, improve the body immunity, reduce toxic and side effects, and the clinical effect is better than conventional chemotherapy.

Liddle syndrome: case report and literature review / 中华全科医师杂志

The clinical data and the genetic study results of a patient with Liddle syndrome were reported.The genomic DNA of peripheral blood mononuclear cells was extracted and the mutation sites of all the exons in 36 genes related to hypokalemia were screened by high-throughput sequencing.Genetic validation of patients and their parents was performed by direct sequencing.The patient presented with severe hypokalemia,low aldosterone and hypertension.The results of gene sequencing showed that the SCNN1B gene exon 13 584 codon 1751C-T,and the corresponding encoded amino acid changed from alanine to valine (A-V).Eleven families and 33 cases of Liddle syndrome diagnosed by genetic analysis were reported in Chinese literature from 1998 to June 2018.The literature review showed that all patients had hypertension,87％ (28/32) had hypokalemia and 85％ (23/27) had low aldosterone.The onset age of 21 patients was＜20 year,among whom cerebral stroke occurred in 3 patients.The normal blood pressure can be achieved by low-salt diet and administration of amiloride or triamterene.The most common mutations were missense mutations (7/11).Liddle syndrome is a controllable and treatable disease,early detection,diagnosis and treatment can avoid serious complications.

Cold temperature and risk of stroke / 国际脑血管病杂志

Many studies indicated that meteorological factors are associated with stroke risk,especially cold temperature.This article reviews the effect of cold temperature on the occurrence of stroke.

Discussion on Cultivation and Practice of Medical Humanistic Quality of Excellent Doctors:Taking Yangtze University as Example / 中国医学伦理学

The humanistic nature of medicine determines that medical humanistic quality training must be car-ried out in the education of excellent doctors. Based on the requirements of excellent doctor"with the aim to culti-vate position competency", Yangtze University, as a pilot institution for the reform of excellent doctors training mode, adopts a comprehensive training mode of medical humanistic quality, incorporates the cultivation of excellent doctors ' medical humanistic quality into the teaching plan to ensure the implementation of medical humanistic qual-ity cultivation institutionally;sets up general education, imparts humanistic knowledge and strengthens humanistic cultivation;integrates medical humanistic quality education into professional education to elevate the height of ex-cellent doctors' medical humanistic quality; integrates medical humanistic quality into clinical practice as an im-portant clinical ability;reforms teaching methods of medical humanistic quality and emphasizes the quality of medi-cal humanistic education, and carries out the student characteristic activity of"Xinglin Cultural Festival"and"The 8 One" to shape the student healthy personality and cultivate their healthy psychology.

Prognostic significance of preoperative neutrophil-lymphocyte ratio combined with tu-mor-associated neutrophils in patients with gastric cancer / 中国肿瘤临床

Objective:To investigate the prognostic significance of preoperative neutrophil-lymphocyte ratio(NLR)combined with tu-mor-associated neutrophils(TANs)in the stroma of gastric cancer tissues of patients.Methods:One hundred and twenty-six gastric cancer tissue samples from patients enrolled in Changhai hospital from June 2006 to May 2011 were divided into four groups accord-ing to NLRs in preoperative peripheral blood combined with high or low infiltration of neutrophils in gastric cancer tissues.The 5-year survival of the four groups was then compared,and their correlations with clinicopathologic features and prognosis were analyzed.Re-sults:High NLRs in peripheral blood combined with low infiltrating TANs in gastric tissues was associated with lower differential grade (P<0.001)and larger tumor size(P=0.026).Of the four groups,patients with high NLR in peripheral blood combined with low infiltrat-ing TANs in gastric cancer tissues demonstrated the lowest survival rates,whereas those with low NLR and high infiltrating TANs had highest survival rates, and this difference was statistically significant (P<0.05). Univariate and multivariate Cox regression analyses showed that high NLR in peripheral blood combined with low infiltrating TANs in gastric cancer tissues(P<0.05)was an independent factor indicating poor prognosis.Conclusions:NLR in preoperative peripheral blood combined with infiltrating TANs in gastric cancer tissues can be used as a prognostic indicator for patients with gastric cancer,especially high NLR in preoperative peripheral blood com-bined with low infiltrating TANs in gastric cancer tissue indicates poor prognosis.

Screening of aptamer binding to lipopolysaccharide of Pseudomonas aeruginosa and analysis of its inhibi-tory effect on macrophage polarization / 中华微生物学和免疫学杂志

Objective To screen high-affinity aptamers binding to the surface lipopolysaccharide (LPS) of Pseudomonas aeruginosa (PA), and to analyze their inhibitory effects on macrophage polarization. Methods LPS of PA was ectracted and purified. High-affinity aptamers binding to the LPS of PA were screened by systematic evolution of ligands by exponential enrichment (SELEX). Enzyme-linked oligonucleotide assay (ELONA) and quantitative PCR (Q-PCR) were performed to investigate their influences on macrophage polarization. Results In this study, an aptamer PL-6 that could specifically bind to PA-LPS was screened suc-cessfully and found to be able to block the binding of PA-LPS to the corresponding receptor TLR4, inhibit mac-rophage M1 polarization and maintain macrophage homeostasis. Conclusion This study found a high-affinity aptamer binding to the LPS of PA, which might provide a new strategy for the prevention and treatment of sepsis caused by PA.