[Analysis of risk factors for lymph node metastasis in 1096 patients with early gastric cancer and establishment of a predictive nomogram].

Objective: To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk. Methods: The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC). Results: A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P<0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323-23.572, P<0.001), undifferentiated type (OR=3.095, 95%CI: 1.649-5.811, P<0.001), tumor T1b (OR=1.798, 95%CI: 1.053-3.079, P=0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031-1.469, P=0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P>0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849-0.911) and 0.881 (95%CI: 0.841-0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746-0.809, P<0.001). Conclusions: Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Trends, challenges, and reflections on early-onset gastric cancer].

Early onset gastric cancer (EOGC), as a distinct type of gastric cancer, has seen a gradually increasing incidence in recent years, imposing significant negative impacts on society and families, and has attracted widespread attention. EOGC presents a series of clinical characteristics, such as a higher prevalence among women, pathological types predominantly being poorly differentiated or undifferentiated, and Lauren classification often being diffuse, making it more prone to distant metastasis. However, the causes and mechanisms of its onset are not yet fully understood. Notably, about 10% of EOGC cases exhibit familial clustering and germline mutations in the Cadherin-1 (CDH1) or α-1 catenin (CTNNA1) genes, known as hereditary diffuse gastric cancer (HDGC). These unique clinical features pose significant challenges for the diagnosis and treatment of EOGC. The core of treatment for early onset gastric cancer focuses on strong efficacy, function preservation, rehabilitation, and social reintegration. Clinically, a multidisciplinary approach and comprehensive treatment are essential, with equal emphasis on physiological and psychological aspects, balancing therapeutic effectiveness with functional outcomes, to benefit more patients with EOGC.

[Clinicopathological features and prognosis of early-onset gastric cancer: a large-scale retrospective real-world study].

Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group (P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ2=6.247, P=0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

[Diagnosis and treatment of arrhythmogenic cardiomyopathy in children].

Objective: To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children. Methods: A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022. Results: A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable. Conclusions: ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.

[Risk prediction and function evaluation by T-cell epitope model and expression model of HLA-DPB1 mismatching in unrelated-donor hematopoietic stem cell transplantations].

Objective: To evaluate the risk prediction and assessment function of HLA-DPB1 T-cell epitope (TCE) model and expression model in human leukocyte antigen (HLA)-matched unrelated hematopoietic stem cell transplantation (MUD-HSCT) with HLA-DPB1 mismatching. Methods: A total of 364 (182 pairs) potential MUD-HSCT donors and recipients confirmed by HLA high-resolution typing in Shaanxi Blood Center from 2016 to 2019 were analyzed retrospectively. Of the 182 recipients, there were 121 males and 61 females with an average age of (26.3±14.2) years. Of the 182 donors, there were 148 males and 34 females with an average age of (33.7±7.5) years. Polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) based on LABScan®3D platform were used for high-resolution typing of HLA-A, B, C, DRB1, DQB1, DPB1 gene, and PCR-SBT was used for single nucleotide polymorphism (SNP) typing. TCE model and expression model were used to predict and evaluate the HLA-DPB1 mismatch pattern and acute graft-versus-host-disease (aGVHD) risk. Results: A total of 26 HLA-DPB1 alleles and their 3'-UTR rs9277534 SNP genotypes were detected in this study population, and two new alleles HLA-DPB1*1052∶01 and HLA-DPB1*1119∶01 were found and officially named. The overall mismatch rate of HLA-DPB1 in MUD-HSCT donors and recipients was 90.66% (165/182). In TCE model, the HLA-DPB1 mismatch rates of permissible mismatch (PM) and non-permissible mismatch (non-PM) were 47.80% (87/182) and 42.86% (78/182), respectively. The non-PM in GvH direction was 13.73% (25/182), and which in HvG direction was 29.12% (53/182). A total of 73 pairs of donors and recipients in TCE model met the evaluation criteria of expression model. Among of TCE PM group, recipient DP5 mismatches accounted for 34.25% (25/73) were predicted as aGVHD high risk according to expression model. For the TCE non-PM group, both the recipient DP2 mismatches of 6.85% (5/73) and recipient DP5 mismatches of 10.86% (8/73) were predicted to be at high risk for aGVHD. Risk prediction by TCE model and expression model was 27.27% concordant and 16.97% unconcordant. Conclusions: TCE model and expression model are effective tools to predict aGVHD risk of MUD-HSCT. Comprehensive application of the two models is helpful to the hierarchical assessment of HSCT risk.

[Analysis of iodine nutritional status of children aged 8-10 years in Zhejiang Province from 2016 to 2021].

Objective: To analyze the iodine nutrition status of children aged 8 to 10 years in Zhejiang Province from 2016 to 2021. Methods: A multi-stage stratified sampling method was used to select non-residential children aged 8 to 10 years from 90 counties in Zhejiang Province. A total of 114 103 children were included in the study from 2016 to 2021. Direct titration method and arsenic-cerium catalytic spectrophotometry were used to detect salt iodine content and urinary iodine level, respectively, to evaluate the iodine nutritional status of children. Ultrasound was used to detect thyroid volume and analyze the current prevalence of goiter in school-age children. Results: The age of 114 103 children was (9.04 ± 0.81) years old, with 50.0% of (57 083) boys. The median of iodine content M (Q1, Q3) in children's household salt was 23.00 (19.80, 25.20) mg/kg, including 17 242 non-iodized salt, 6 173 unqualified iodized salt, and 90 688 qualified iodized salt. The coverage rate of iodized salt was 84.89%, and the coverage rate of qualified iodized salt was 79.48%. The proportion of non-iodized salt increased from 11.85% in 2016 to 16.04% in 2021 (χ2trend=111.427, P<0.001). The median of urinary iodine concentration M (Q1, Q3) in children was 182.50 (121.00, 261.00) µg/L, among which the proportions of iodine deficiency, iodine suitability, iodine over suitability, and iodine excess were 17.25% (19 686 cases), 39.21% (44 745 cases), 26.85% (30 638 cases), and 16.68% (19 034 cases), respectively. The median of urinary iodine concentration in children in inland areas [M (Q1, Q3): 190.90 (128.80, 269.00) µg/L] was significantly higher than that in children in coastal areas [M (Q1, Q3): 173.00 (113.00, 250.30) µg/L] (P<0.001). From 2016 to 2021, a total of 39 134 ultrasound examinations were conducted, and 1 229 cases of thyroid enlargement were detected. The goiter rate was 3.14% (95%CI: 2.97%-3.32%). The incidence of goiter in children in coastal areas [3.45% (95%CI: 3.19%-3.72%), 641/18 604] was higher than that in children in inland areas [2.86% (95%CI: 2.64%-3.10%), 588/20 530] (P=0.001). Conclusion: From 2016 to 2021, the iodine nutrition level of children aged 8-10 years in Zhejiang Province is generally suitable, and the rate of goiter in children meets the limit of iodine deficiency disease elimination standards.

A comparison of size exclusion chromatography-based tandem strategies for plasma exosome enrichment and proteomic analysis.

Proteomic analysis of exosomes from human plasma faces a tremendous challenge mainly due to the low abundance of the exosome itself and the complexity of the plasma matrix. Therefore, enrichment of exosomes from human plasma is an essential and indispensable step for large scale and in depth proteomic analysis. Size exclusion chromatography (SEC) is one of the most extensively used methods for exosome isolation from human plasma and many SEC-based tandem methods were established in order to increase the purity of the enriched exosomes and thus the accuracy of the proteomic analysis. To compare the advantages and disadvantages of the different isolation methods and subsequently to promote the establishment of a standardized method for plasma proteomic research, the capacities of the direct SEC method, the combination of SEC with ultracentrifugation (SEC-UC), ultrafiltration (SEC-UF), and titanium dioxide microspheres (SEC-TiO2) were systematically evaluated for exosome isolation from human plasma and thus proteomic analysis. The results demonstrated that the SEC-based tandem methods were superior to the direct SEC method in the purity of exosomes isolated from human plasma. Additionally, the SEC-UC method possessed the highest number of the total identified proteins and the overlapped proteins with the top 100 exosome markers in comparison with the other methods. The SEC-TiO2 method displayed the biggest capacity for plasma protein deleting. We expect that the research will have more beneficial values in the field of exosome research.

Sarcopenia and its clinical correlation in elderly chronic obstructive pulmonary disease: a prospective cohort study.

OBJECTIVE: The aim of this study was to examine the effects of sarcopenia on clinical characteristics and short-term outcomes in elderly chronic obstructive pulmonary disease (COPD) patients. PATIENTS AND METHODS: One hundred twenty elderly COPD patients (age>60) recruited from Beijing Shijingshan Hospital were divided into sarcopenia and non-sarcopenia groups according to the severity of sarcopenia at the first admission. Baseline data, geriatric syndrome, laboratory indicators and body composition analysis were analyzed. One year followed-up by outpatient visits was focused on clinical characteristics and telephone follow-ups for collecting all-cause deaths and acute exacerbations of chronic obstructive pulmonary disease as end-point events. The risk factors for sarcopenia were analyzed by univariate analysis and multivariate logical regression. The proportional hazards model (COX) regression was performed to determine the effect of sarcopenia on COPD patients' prognoses. RESULTS: One hundred twenty patients (76 men and 44 women) with an average age of 76.7±8.78 years were included, of which 63 patients (52.5%) were diagnosed with sarcopenia. Compared to the non-sarcopenia group, the sarcopenia group exhibited worse lung function and more severe geriatric syndromes with significantly higher incidence ratios of somnipathy and frailty. The sarcopenia group also showed worse muscle indicators and declined body composition. Multivariate analysis showed that the occurrence of sarcopenia in elderly COPD patients was correlated with forced expiratory volume in the first second (FEV1) (OR=0.97, 95% CI: 0.94-1.0, p=0.035), body mass index (BMI) (OR=0.80, 95% CI: 0.71-0.89, p=0.035) and hemoglobin (OR=0.98, 95% CI: 0.96-1.0, p=0.023). Furthermore, the COX regression indicated the association of sarcopenia with acute exacerbations of COPD within the follow-up period (HR=2.4, 95% CI: 1.01-5.72, p=0.048). CONCLUSIONS: Sarcopenia increases the risk of acute exacerbations of chronic obstructive pulmonary disease in the elderly. Sarcopenia incidence in elderly COPD is associated with FEV1, BMI, and hemoglobin and closely monitoring indicators is useful for early diagnosis of sarcopenia.

[Clinicopathological and molecular diagnostic features of early-onset gastric cancer: a study based on data from a single-center dedicated gastric cancer database].

Objective: To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies. Methods: In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups. Results: The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ2=5.442,P<0.001). HER-2 and Epstein-Barr virus positivity rates did not differ significantly between the two groups. Conclusion: Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

[Clinical efficacy of femoral neck screw system combined with supported hollow screw in treatment of femoral neck fractures with posterometral comminution in young and middle-aged patients].

Objective: To investigate the clinical efficacy of dynamic cross screw system (FNS) for femoral neck fractures in young and middle-aged patients with posterior medial comminution. Methods: A retrospective cohort study. Clinical data of 197 young and middle-aged patients with femoral neck fractures accompanied by posterior medial comminution treated with closed reduction FNS and internal fixation with anti-rotation cannulated screws in Beijing Luhe Hospital, Beijing Jishuitan Hospital and Beijing Tongren Hospital from October 2019 to October 2021 were analyzed retrospectively. According to different surgical methods, the patients were divided into two groups. There were 102 patients in the FNS group, included 55 males and 47 females with a mean age of (40.49±19.79) years; and there were 95 patients in the FNS plus anti-rotation hollow screw group (combined group), included 51 males and 44 females with an average age of (40.03±18.82) years. All patients were followed-up for at least 1 year after surgery. The general clinical data, surgical conditions and Harris score of the hip joint at the last follow-up of the two groups were compared. And the clinical efficacy of the two surgical schemes were evaluated and compared. After surgery, routine X-ray and CT examinations were performed to evaluate the fracture reduction and internal fixation, and the shortening of the femoral neck on the affected side was compared to that of healthy side according to the Zlowodzki method. Results: At the last follow-up, the incidence of fracture reduction loss, screw resection and coxa vara in the combined group were all significantly lower than those in the FNS group [10 (10.5%) vs 28 (27.4%), 1 (1.0%) vs 7 (6.8%) and 9 (9.4%) vs 21 (20.5%), respectively, all P<0.05]. The incidence of nonunion and necrosis of the femoral head in the combined group were both lower than those in the FNS group, but there was no significant difference between two groups (both P>0.05). The postoperative mild, moderate and severe femoral neck shortening in the combined group were all lower than those in the FNS group, and the difference were not statistically significant (all P>0.05). At the last follow-up, the Harris score in the combined group was 84.60±2.08, and it was higher than that in the FNS group (79.57±4.31), but the difference was not statistically significant (P=0.403). Conclusion: FNS plus supporting hollow screw has a good clinical effect on femoral neck fractures in young and middle-aged adults with posterior medial comminution.

Digitalization of hydraulic rotary drilling process for continuously mechanical profiling of siliciclastic sedimentary rocks.

Hydraulic rotary drilling can offer the essential information and core samplesa for the researches on solid earth. Recording the factual field drilling data and analyzing the hydraulic rotary coring process are challenging yet promising to utilize the massive drilling information in geophysics and geology. This paper adopts the drilling process monitoring (DPM) technique and records the four parameters of displacement, thrust pressure, upward pressure, and rotation speed in real-time series for profiling the siliciclastic sedimentary rocks along 108 m deep drillhole. The digitalization results with 107 linear zones represent the spatial distribution of drilled geomaterials including superficial deposits (fill, loess, gravelly soil), mudstone, silty mudstone, gritstone, and fine sandstone. The constant drilling speeds varying from 0.018 to 1.905 m/min present the in-situ coring resistance of drilled geomaterials. Furthermore, the constant drilling speeds can identify the strength quality of soils to hard rocks. The thickness distributions of the six basic strength quality grades are presented for all the sedimentary rocks and each individual type of the seven soil and rocks. The in-situ strength profile determined in this paper can be used to assess and evaluate the in-situ mechanical behavior of geomaterial along the drillhole and can provide a new mechanical-based assessment for determining the spatial distribution of geological strata and structures in subsurface. They are important since the same stratum at different depths can have different mechanical behavior. The results provide a novel quantitative measurement for continuously in-situ mechanical profiling by digital drilling data. The findings of the paper can offer a new and effective method for refinement and upgrading of in-situ ground investigation, and can provide researchers and engineers with a novel tool and valuable reference to digitize and utilize factual data of current drilling projects.

[PIK3CA gene mutations in Chinese women with HR+/HER2- breast cancer].

Objective: To investigate the spectrum of PIK3CA gene mutations in Chinese women with hormone receptor positive and HER2 negative (HR+/HER2-) breast cancer, to provide the genetic evidence for identifying potential beneficiaries from specific PI3K isoform inhibitors in Chinese women with breast cancer and to develop detection strategies. Methods: A total of 365 breast cancer specimens archived at the Peking Union Medical College Hospital, Beijing, China from January 2017 to October 2017 were screened. Among these patients, 186 HR+/HER2- women with invasive breast cancer were collected. PIK3CA gene mutations were detected using next generation sequencing technology. The gene variant features were then analyzed and compared with reported data. Results: Among the 186 HR+/HER2- breast cancer cases, 40 (21.5%,40/186) cases harbored PIK3CA gene mutations. Exons 9 and 20 of PIK3CA mutations occurred in 92.5%(37/40)of the tumors, which included E545K, E545G, Q546K, E542K, Q546R, P539R, E547D, H1047R, H1047L, H1047Q and N1044Y. Only one case harbored the exon 7 C420R mutation. Additionally, exons 1 (F83C) and 5 (G364R) uncommon mutations were discovered respectively in 2 cases. Based on the finding, 85.0% (34/40) of cases with known mutations could be detected using companion diagnostic methods. Moreover, 25.0% (10/40) of patients had two or three variants, which were composed of E726K/N345K, H1047Q/N345K, H1047R/G364R, H1047R/E453K, E545G/E726K, E542K/E726K, E542K/H1047R, E545K/H1047R/H1047L and E545K/E547D. The lymph node positive rate in these patients with PIK3CA mutation was remarkably higher than those without (i.e., wild type, P<0.05). Conclusions: In this group of HR+/HER2- breast cancer patients, common PIK3CA gene mutations account for the vast majority of the mutations. New rare variants in PIK3CA are also identified while their clinical significance needs to be further studied in a large cohort and/or multi-center study.

[Experience in emergency response to 2019-nCoV positive cases in an international test competition].

Objective: To analyze the performance of emergency response to 2019 novel coronavirus (2019-nCoV) positive cases in an international test competition in an Winter Olympic Game venue and provide evidences for the COVID-19 prevention and control in similar competitions. Methods: A retrospective analysis on the epidemiological investigation and nucleic acid test results of the cases, the implementation of prevention and control measures, including the communication with sport teams and others, was conducted. Results: The positive cases of 2019-nCoV among entering people were detected before entry, at airport, hotel and venue. Two positive cases were reported before entry, 2 positive cases infected previously and 3 asymptomatic cases were reported after the entry. The venue public health team and local CDC conducted epidemiological investigation and contact assessment jointly in a timely and efficient manner. No local secondary transmission occurred, but the nucleic acid test results of positive persons fluctuated, posing serious challenges to the implementation of prevention and control measures. Conclusion: In large scale international competition, there is high risk of imported COVID-19. It is necessary to fully consider the fluctuation of nucleic acid test results, the criteria for determination and cancellation of positive results and give warm care to positive cases in the emergency response.

A systematic study on 33 gallbladder stones resembling adult Clonorchis sinensis worms.

Limited studies provide direct evidence of Clonorchis sinensis adults in the early stage of gallbladder stone formation. Our current research systematically studied 33 gallbladder stones resembling adult worms and shed light on the definite connection of C. sinensis infection with concomitant cholelithiasis. A total of 33 gallbladder stones resembling adult C. sinensis worms were systematically analysed. Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray energy spectrometry were used to analyse the composition and microstructure. Meanwhile, a histopathological examination of the stone was carried out. The 33 gallbladder stones resembling adult C. sinensis worms included nine calcium carbonate (CaCO3) stones, 12 bilirubinate stones and 12 mixed stones. Clonorchis sinensis eggs were found in 30 cases, including all CaCO3 and mixed stones. Parasite tissues were detected in 12 cases, which were mainly CaCO3 stones or bilirubinate-CaCO3 mixed stones. The outer layer of stones was wrapped with 12.88% calcium salt, as revealed by X-ray energy spectrometry, while surprisingly, many C. sinensis eggs were found in the inner part of these stones. Based on our current findings, we concluded that calcification and packaging occurred after C. sinensis adult entrance into the gallbladder, subsequently leading to the early formation of CaCO3 or bilirubinate-CaCO3 mixed gallbladder stones. This discovery highlights definite evidence for C. sinensis infection causing gallbladder stones.

The combined impact of xylo-oligosaccharides and gamma-irradiated astragalus polysaccharides on the immune response, antioxidant capacity, and intestinal microbiota composition of broilers.

The present study investigated the individual and combined effects of xylo-oligosaccharides (XOS) and gamma-irradiated astragalus polysaccharides (IAPS) on the immune response, antioxidant capacity and intestinal microbiota composition of broiler chickens. A total of 240 newly hatched Ross 308 chicks were randomly allocated into 5 dietary treatments including the basal diet (control), or the basal diet supplemented with 50 mg/kg chlortetracycline (CTC), 100 mg/kg XOS (XOS), 600 mg/kg IAPS (IAPS), and 100 mg/kg XOS + 600 mg/kg IAPS (XOS + IAPS) respectively. The results showed that birds in the control group had lower the thymus index and serum lysozyme activity than those in the other 4 groups (P < 0.05). Moreover, there was an interaction between XOS and IAPS treatments on increasing the serum lysozyme activity (P < 0.05). Birds in the CTC and XOS + IAPS groups had lower serum malondialdehyde concentration and higher serum total antioxidant capacity activity and mucosal interleukin 2 mRNA expression of jejunum than those in the control group (P < 0.05). In addition, birds in the control groups had lower duodenal and jejunal IgA-producing cells number than these in other 4 groups (P < 0.05). As compared with the CTC group, dietary individual XOS or IAPS administration increased duodenal IgA-producing cells number (P < 0.05). Meanwhile, there was an interaction between XOS and IAPS treatments on increasing duodenal and jejunal IgA-Producing cells numbers (P < 0.05). Dietary CTC administration increased the proportion of Bacteroides, and decreased the proportion of Negativibacillus (P < 0.05). However, dietary XOS + IAPS administration increased Firmicutes to Bacteroidetes ratio, the proportion of Ruminococcaceae, as well as decreased the proportion of Barnesiella and Negativibacillus (P < 0.05). In conclusion, the XOS and IAPS combination could improve intestinal mucosal immunity and barrier function of broilers by enhancing cytokine gene expression, IgA-producing cell production and modulates cecal microbiota, and the combination effect of XOS and IAPS is better than that of individual effect of CTC, XOS, or IAPS in the current study.