Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20⁺B cells, CD4⁺T cells, and FOXP3⁺Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20⁺B cells, CD4⁺T cells and FOXP3⁺Treg cells in LELC may suggest a better prognosis.
Humans ; Lymphocytes, Tumor-Infiltrating ; Herpesvirus 4, Human ; Clinical Relevance ; Prognosis ; Carcinoma, Squamous Cell/pathology* ; Forkhead Transcription Factors

Accurate pathology diagnosis of breast cancer is the premise of personalized treatment. In recent years, the pathology diagnosis of breast cancer have been updated and optimized to provide better guidance and basis for clinical treatment. In this paper, we provide an overview on the advances in histological classification of breast cancer, the progress of biomarker detection related to novel antibody-drug conjugates and immunotherapy in breast cancer, the pathology evaluation of breast cancer specimen after neoadjuvant therapy and sentinel lymph nodes, the progress of genetic testing in breast cancer, and the application of artificial intelligence in breast pathology.
Female ; Humans ; Artificial Intelligence ; Breast ; Breast Neoplasms ; Immunotherapy ; Neoadjuvant Therapy

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.
China ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen ; Neoadjuvant Therapy ; Retrospective Studies ; Trastuzumab ; Humans ; Female ; Breast Neoplasms/drug therapy*

OBJECTIVE: To evaluate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute kidney injury induced by acute liver failure and unravel the underlying mechanism, so as to provide insights into the clinical therapy of acute kidney injury. METHODS: Twenty-four male C57BL/6J mice at ages of 6 to 8 weeks were randomly divided into the normal control group, rSj-Cys control group, lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) model group and LPS/D-GaIN + rSj-Cys treatment group, of 6 mice each group. Mice in the LPS/D-GaIN group and LPS/D-GaIN + rSj-Cys group were intraperitoneally injected with LPS (10 μg/kg) and D-GaIN (700 mg/kg), and mice in the LPS/D-GaIN + rSj-Cys group were additionally administered with rSj-Cys (1.25 mg/kg) by intraperitoneal injection 30 min post-modeling, while mice in the rSj-Cys group were intraperitoneally injected with rSj-Cys (1.25 mg/kg), and mice in the normal control group were injected with the normal volume of PBS. All mice were sacrificed 6 h post-modeling, and mouse serum and kidney samples were collected. Serum creatinine (Cr) and urea nitrogen (BUN) levels were measured, and the pathological changes of mouse kidney specimens were examined using hematoxylin-eosin (HE) staining. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were detected using enzyme-linked immunosorbent assay (ELISA), and the expression of inflammatory factors and pyroptosis-related proteins was quantified in mouse kidney specimens using immunohistochemistry. In addition, the expression of pyroptosis-related proteins and nuclear factor-kappa B (NF-κB) signaling pathway-associated proteins was determined in mouse kidney specimens using Western blotting assay. RESULTS: HE staining showed no remarkable abnormality in the mouse kidney structure in the normal control group and the rSj-Cys control group, and renal tubular injury was found in LPS/D-GaIN group, while the renal tubular injury was alleviated in LPS/D-GaIN+rSj-Cys treatment group. There were significant differences in serum levels of Cr (F = 46.33, P < 0.001), BUN (F = 128.60, P < 0.001), TNF-α (F = 102.00, P < 0.001) and IL-6 (F = 202.10, P < 0.001) among the four groups, and lower serum Cr [(85.35 ± 32.05) μmol/L], BUN [(11.90 ± 2.76) mmol/L], TNF-α [(158.27 ± 15.83) pg/mL] and IL-6 levels [(56.72 ± 4.37) pg/mL] were detected in the in LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (all P values < 0.01). Immunohistochemical staining detected significant differences in TNF-α (F = 24.16, P < 0.001) and IL-10 (F = 15.07, P < 0.01) expression among the four groups, and lower TNF-α [(106.50 ± 16.57)%] and higher IL-10 expression [(91.83 ± 5.23)%] was detected in the LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (both P values < 0.01). Western blotting and immunohistochemistry detected significant differences in the protein expression of pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3 (NLRP3) (F = 24.57 and 30.72, both P values < 0.001), IL-1β (F = 19.24 and 22.59, both P values < 0.001) and IL-18 (F = 16.60 and 19.30, both P values < 0.001) in kidney samples among the four groups, and lower NLRP3, IL-1β and IL-18 expression was quantified in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (P values < 0.05). In addition, there were significant differences in the protein expression of NF-κB signaling pathway-associated proteins p-NF-κB p-P65/NF-κB p65 (F = 71.88, P < 0.001), Toll-like receptor (TLR)-4 (F = 45.49, P < 0.001) and p-IκB/IκB (F = 60.87, P < 0.001) in mouse kidney samples among the four groups, and lower expression of three NF-κB signaling pathway-associated proteins was determined in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (all P values < 0.01). CONCLUSIONS rSj-Cys may present a protective effect against acute kidney injury caused by acute liver failure through inhibiting inflammation and pyroptosis and downregulating the NF-κB signaling pathway.
Mice ; Male ; Animals ; Interleukin-10 ; Tumor Necrosis Factor-alpha/genetics* ; NF-kappa B/therapeutic use* ; Interleukin-18/therapeutic use* ; Schistosoma japonicum/metabolism* ; Interleukin-6/therapeutic use* ; Lipopolysaccharides/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice, Inbred C57BL ; Acute Kidney Injury/drug therapy* ; Liver Failure, Acute ; Cystatins/therapeutic use*

Objective: To study the willingness and influence factors related to "centralized slaughtering, fresh poultry listing and marketing" strategy, among the household chefs, and provide reference for government to adjust and optimize the strategy on avian influenza prevention. Methods: According to the geographical characteristics and regional functions, 6 'monitoring stations' were selected from 12 residential districts of Guangzhou, respectively. Another 21 meat markets which selling live poultry, were selected in each station and 5 household chefs of each market were invited to attend a face to face interview. Basic information, personal cognitive, willingness and influencing factors to the policy were under study. Univariate and multivariate logistic regression methods were used. Results: A total of 664 household chefs underwent the survey and results showed that the rate of support to the "centralized slaughtering, fresh poultry listing and marketing" strategy was 44.6% (296/664). Results from the multi-factor logistic regression showed that those household chefs who were males (OR=1.618, 95% CI: 1.156-2.264, P=0.005), having received higher education (OR=1.814, 95% CI: 1.296-2.539, P=0.001), or believing that the existence of live poultry stalls was related to the transmission of avian influenza (OR=1.918, 95% CI: 1.341-2.743, P<0.001) were factors at higher risk. These household chefs also intended to avoid the use of live poultry stalls (OR=1.666, 95%CI: 1.203-2.309, P=0.002) and accept the "centralized slaughtering, fresh poultry listing and marketing" strategy. Conclusion: Detailed study on this subject and, setting up pilot project in some areas as well as prioritizing the education programs for household chefs seemed helpful to the implementation of the 'freezing-fresh poultry' policy.
Animals ; Attitude to Health ; China ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza in Birds ; Influenza, Human/prevention & control* ; Male ; Marketing ; Meat-Packing Industry ; Multivariate Analysis ; Pilot Projects ; Poultry/virology* ; Surveys and Questionnaires

Objective: To study the prevalence and characteristics of overweight and obesity among Chinese children aged 0-5 years, in 2010-2013. Methods: Data was from the'China Nutrition and Health Surveillance-0-5-Years-Old Children and Lactating Women'project in 2013. Stratified multistage cluster sampling method was used to select 55 districts/counties from 30 provinces (autonomous regions, municipalities) with the sample size of children as 32 862. Definition of overweight and obesity were according to both the WHO 2006 growth standard in children less than 5-year-old and the WHO 2007 growth reference in children of 5-years-old. Results: were calculated by complex weight based on national census from the National Bureau of Statistics in 2010. Results The overall prevalence of overweight was 8.4% among the 0-5-year-old in 2013, with 9.4% in boys and 7.2% in girls. Both of the rates from urban and rural areas were the same, as 8.4%. The prevalence rates of overweight in the 0-, 6-, 12-, 24-, 36-, 48- and 60-71 months age groups appeared as 13.0%, 11.1%, 8.3%, 6.0%, 4.8%, 3.9% and 15.9%, respectively. The rates of overweight in low, medium and high income families were 8.0%, 8.8% and 8.9%, respectively. The prevalence of obesity was 3.1% among the 0-5-year-old, with 3.6% in boys and 2.5% in girls. There was no significant difference seen in urban (3.3%) and rural areas (2.9%). The prevalence rates for obesity in the 0-, 6-, 12-, 24-, 36-, 48- and 60-71 months age groups were 5.8%, 3.8%, 2.5%, 1.6%, 1.2%, 1.3% and 7.8%, respectively. The rates of obesity in low, medium and high income families were 2.8%, 3.3% and 3.5%, respectively. Conclusion: The prevalence rates of both overweight and obesity were increasing among the 0-5-year-olds in China, suggesting that it is necessary to timely conduct the surveillance and intervention programs on overweight and obesity in this target population.
Adolescent ; Asian People/statistics & numerical data* ; Body Mass Index ; Body Weight ; Child ; Child, Preschool ; China/epidemiology* ; Female ; Humans ; Income ; Infant ; Infant, Newborn ; Lactation ; Male ; Nutritional Status ; Obesity/ethnology* ; Overweight/ethnology* ; Prevalence

Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.
Animals ; Chickens ; China ; Commerce ; Humans ; Influenza A Virus, H7N9 Subtype/pathogenicity* ; Influenza in Birds/virology* ; Influenza, Human/virology* ; Phylogeny ; Poultry/virology* ; Real-Time Polymerase Chain Reaction ; Zoonoses

Objective: To understand the epidemiological characteristics of influenza in Guangdong province, during the winter of 2017-2018, to provide evidence for response to the diversity of influenza, in different seasonal patterns. Methods: Data on weekly influenza surveillance from January 2016 to April 2018, were collected in Guangdong. Information on patients with Influenza-like illness (ILI), on influenza virus positive rates and on outbreaks during the winter of 2017 to 2018, was analyzed and compared with those in spring of 2016 and summer of 2017. χ(2) test and Fisher exact test were used. Results: In the above said winter, the average percentage of visits for ILI in 28 hospitals where sentinel surveillance program had been set, was 4.99% (157 235/3 149 656), which was above the level of the same period in the previous five years. The positive rates of influenza virus among samples collected from ILI outpatients and hospitalized cases under severe acute respiratory infection (SARI) were 28.33% (2 137/7 543) and 14.93% (256/1 715), with the proportions of B (Yamagata) as 70.43% (1 505/2 137) and 73.05% (187/256) respectively. A total of 257 influenza outbreaks were reported in the winter period, with 82.49% (212/257) occurred in elementary schools. Cases aged 6-14 years occurred in winter and spring appeared of having higher positive rate than those seen in summer (P<0.05) whereas elderly cases aged 60 and above showed higher positive rate in summer than those in winter and spring two seasons (P<0.05). Conclusions: Epidemiological characteristics of influenza appeared in Guangdong province, during the winter from 2017 to 2018, were correlated to Influenza B (Yamagata). Capacity on the implementation of surveillance programs and on the coverage of vaccination should be improved and increased in order to control influenza in different epidemic seasons, in Guangzhou.
Adolescent ; Adult ; Aged ; Child ; China/epidemiology* ; Disease Outbreaks ; Epidemics ; Humans ; Infant ; Influenza Vaccines/administration & dosage* ; Influenza, Human/virology* ; Middle Aged ; Orthomyxoviridae/isolation & purification* ; Population Surveillance ; Respiratory Tract Infections/epidemiology* ; Seasons ; Sentinel Surveillance ; Vaccination

Objective: To explore the spatio-temporal epidemic trends and related driving effects of meteorological factors on brucellosis in Datong city, Shanxi province, from 2005 to 2015. Methods: We collected the surveillance data on brucellosis and related meteorological data in Datong city from 2005 to 2015, to describe the epidemic characteristics of the disease. Quasi-Poisson distribution lag non-liner model (DLNM) was built to explore the driving effect of monthly meteorological data on the disease. Results: From 2005 to 2015, Datong city reported a total of 17 311 cases of brucellosis including one death, with the annual average incidence as 47.43 per 100 000 persons. A rising trend was seen during the study period. The monthly incidence of Brucellosis presented an obvious curve with a major peak from March to June, accounted for 48.40% of the total cases. The high incidence areas in the city gradually expanded from the northeast and southeast to the western areas. Results from the DLNM studies suggested that seasonality of brucellosis in Datong was significantly affected by metrological factors such as evaporation, rainfall and temperature. The peak of delayed effect appeared the highest when the monthly cumulative evaporation capacity was 140-260 mm and the monthly cumulative rainfall was 20-60 mm with lag less than 1 month or the monthly temperature was -13 ℃ with lag of 4-5 months. Conclusions: The incidence of human brucellosis in Datong city increased significantly from 2005 to 2015. Meteorological factors such as evaporation, rainfall, temperature all showed significant driving effects on the disease.
Brucellosis/epidemiology* ; China/epidemiology* ; Cities ; Climate ; Humans ; Incidence ; Meteorological Concepts ; Space-Time Clustering ; Spatio-Temporal Analysis ; Temperature

Objective: To explore the effects of both pre-gestational BMI and gestational weight gain (GWG) on the birth weight of neonates. Methods: A total of 5 395 pregnant women were selected from the Southwest areas of China (Sichuan/Yunnan/Guizhou) and were divided into groups as pre-gestational underweight, normal weight, overweight and obesity, according to the WHO Recommendation on BMI Classification. Guidelines on Pregnancy weight were adopted from the Institute of Medicine to confirm the accuracy of GWG. Multinomial logistic regression model was used to assess the associations between pregestational BMI and GWG, on the birth weight of the neonates. Results: After adjusting for related confounders, low pre-gestational BMI appeared as a risk factor for SGA (OR=1.91, 95%CI: 1.47-2.50), and was also associated with the decreased risk of LGA (OR=0.55, 95%CI: 0.47-0.66). Inadequate GWG was both associated with the increased risk of delivering SGA (OR=1.57, 95%CI: 1.21-2.03) and the decreased risk of LGA (OR=0.48, 95%CI: 0.41-0.57). Pre-gestational overweight/obesity (OR=1.85, 95%CI: 1.58-2.17) and excessive GWG (OR=1.87, 95%CI: 1.67- 2.11) were both positively associated with the risks on LGA. Data from the stratified analysis indicated that inadequate GWG was positively associated with the risk of SGA among underweight or normal weight women (all P<0.05), but not with those overweight/obese women. Conclusions: Pre-gestational BMI and GWG were important influencing factors on the birth weight of neonates. Health education programs for pregnant women should be intensified and gestational weight gain should also be reasonably under control.
Adult ; Birth Weight ; Body Mass Index ; China ; Female ; Gestational Weight Gain ; Humans ; Infant, Newborn ; Obesity ; Overweight ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Weight Gain