Objective To study the the expression of cytokeratin 5/6(CK5/6)and cell proliferation an-tigen(Ki-67)in apocrine triple-negative breast carcinoma(ATNBC)and their relationship with clinicopatho-logical features and prognosis.Methods Twenty-one patients with pathologically diagnosed invasive apocrine breast cancer and negative estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor-2(Her-2)in this hospital were selected as the ATNBC group,Twenty-two cases in non-ATNBC(NATNBC)were randomly selected as negative control(NATNBC group).The clinical pathological data and follow-up data of all patients were collected,and the expressions of CK5/6 and Ki-67,as well as their relation-ship with clinicopathological characteristics was analyzed.The prognosis in the patients with ATNBC was ana-lyzed.Results There were statistically significant differences in age(P＜0.001),age distribution(P=0.001),histological grading(P＜0.001),and distant metastasis(P=0.020)between the ATNBC group and the NATNBC group(P=0.020).There were 7 cases(33.33％)of CK5/6 positive expression in the ATNBC group and 17 cases(80.95％)in NATNBC group.There was statistically significant difference in the positive expression rate of CK5/6 between the ATNBC group and NATNBC group(P＜0.05).There were 3 cases(14.29％)of Ki-67 high proliferation in the ATNBC group and 17 cases(77.27％)in the NATNBC group.The high proliferation rates of Ki-67 had statistically significant difference between the ATNBC group and NATNBC group(P＜0.05).The positive expression rate of CK5/6 was correlated with the tumor sites and lymph node metastasis in ATNBC patients(P＜0.05).The high proliferation rate of Ki-67 was correlated with nerve invasion in ATNBC patients(P＜0.05).The survival analysis showed that there was statistically significant difference in the 5 years disease-free survival(DFS)rate between the ATNBC group and NATNBC group(P＜0.05).Conclusion ATNBC has its unique clinicopathological features,CK5/6 is less expressed in ATN-BC,the high proliferation of Ki-67 is also less,and the prognosis of ATNBC is better than that of NATNBC.

OBJECTIVE: To explore the effect of interleukin-17A (IL-17A) on liver and kidney injury and prognosis in septic mice. METHODS: A total of 84 SPF male C57BL/6 mice were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis model group (CLP group), and IL-17A intervention group. IL-17A intervention group were then divided into five subgroups according to the dose of IL-17A (0.25, 0.5, 1, 2, 4 μg). Mice in the IL-17A intervention group were intraperitoneally injected with the corresponding dose of IL-17A 100 μL immediately after surgery. The other groups were intraperitoneally injected with 100 μL phosphate buffer solution (PBS). The survival rate of mice was observed at 7 days, and peripheral blood and liver, kidney and spleen tissues were collected. According to the 7-day survival, another 18 mice were randomly divided into Sham group, CLP group, and 1 μg IL-17A intervention group. Peripheral blood samples were collected at 12 hours and 24 hours after CLP, and the mice were sacrificed to obtain liver, kidney, and spleen tissues. The behavior and abdominal cavity of each group were observed. The levels of peripheral blood liver and kidney function indexes and inflammatory factors were detected. The histopathological changes of liver and kidney were observed under light microscope. The peripheral blood and spleen tissues were inoculated in the medium, the number of bacterial colonies was calculated, and the bacterial migration of each group was evaluated in vitro. RESULTS: Except for the Sham group, the 7-day survival rate of mice in the 1 μg IL-17A intervention group was the highest (75.0%), so this condition was selected as the intervention condition for the subsequent study. Compared with Sham group, the liver and kidney functions of CLP group were significantly damaged at each time point after operation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (SCr) reached the peak at 24 hours after operation, and the liver and kidney pathological scores reached the peak at 7 days after operation, the levels of inflammatory cytokines interleukin (IL-17A, IL-6, IL-10) reached the peak at 12 hours after operation, and tumor necrosis factor-α (TNF-α) reached the peak at 24 hours after operation. In addition, a large number of bacteria proliferated in the peripheral blood and spleen, which reached the peak on day 7. Compared with the CLP group, exogenous administration of 1 μg IL-17A significantly delayed the rising trend of each index in the early stage of sepsis [24-hour ALT (U/L): 166.95±5.20 vs. 271.30±6.11, 24-hour AST (U/L): 599.42±7.25 vs. 1 013.27±3.37, 24-hour BUN (mg/L): 815.4±26.3 vs. 1 191.2±39.4, 24-hour SCr (μmol/L): 29.34±0.87 vs. 60.75±3.83, 7-day liver pathological score: 2.50 (2.00, 3.00) vs. 9.00 (8.50, 9.00), 7-day kidney pathological score: 1.00 (1.00, 2.00) vs. 5.00 (4.50, 5.00), 12-hour IL-17A (ng/L): 105.21±0.31 vs. 111.28±1.37, 12-hour IL-6 (ng/L): 83.22±1.01 vs. 108.88±0.99, 12-hour IL-10 (ng/L): 731.54±3.04 vs. 790.25±2.54, 24-hour TNF-α (μg/L): 454.67±0.66 vs. 576.18±0.76, 7-day peripheral blood colony count (CFU/mL): 600 (400, 600) vs. 4 200 (4 200, 4 300), 7-day spleen tissue colony count (CFU/g): 4 600 (4 400, 4 600) vs. 23 400 (23 200, 23 500), all P < 0.05]. CONCLUSIONS Appropriate dose (1 μg) of exogenous IL-17A can reduce the lethal inflammatory response induced by CLP and improve the ability of bacterial clearance, thereby alleviating liver and kidney injury and improving the 7-day survival rate of septic mice.
Animals ; Male ; Mice ; Interleukin-10 ; Interleukin-17/pharmacology* ; Interleukin-6 ; Kidney/physiopathology* ; Liver/physiopathology* ; Mice, Inbred C57BL ; Prognosis ; Sepsis ; Tumor Necrosis Factor-alpha

Abstract： Objective　To retrospectively analyze the investigation and disposal of the COVID-19 outbreak caused by the transmission of the Omicron variant in infected imported cases, and provide basis for COVID-19 outbreak management. Methods　The description epidemiological method was used to describe the COVID-19 outbreak in Sanya City from March 31 to April 15, 2022. The propagation chain was mapped and the experience gained and shortcomings identified in emergency responses were analyzed. Results　The outbreak resulted in 95 reported locally transmitted COVID-19 cases with a incubation period M(P25, P75) of 4 (3, 5) d. In the 95 cases, the proportion of cases detected through close contact screening, centralized isolation, community screening, control area screening, active treatment (examination), and key population screening were 33.68%, 22.11%, 18.95%, 12.63%, 6.32%, 4.21% and 2.11%, respectively. The epidemic spread for 6 generations, causing 5 clusters of outbreaks and 12 cases of cluster disease. The epidemic affected 12 villages/neighborhood committees, 1 bar, 1 hospital, 1 small clinic, 1 farmer's market, 1 large shopping mall and 1 restaurant in 2 districts of Sanya City. The result of gene sequencing was Omicron variant BA.1.1. Through the immediate launch of emergency plans, nucleic acid and antigen testing, controlling close contact between infected persons and close contacts, suspending indoor business sites, central urban control, and temporary suspension, COVID-19 was controlled within 16 days. Conclusions　The transmission chain of this outbreak was clear and was caused by imported cases. Strengthening the management of the pass, doing a good job in information sharing and docking, timely screening for cases, screening, pushing, controlling high-risk groups, and implementing comprehensive control measures, can effectively prevent the spread of the epidemic, providing a reference for the control of epidemic situations in relevant scenarios.

Objective:To investigate the patients with hepatocellular carcinoma suitable for transcatheter arterial chemoembolization (TACE) after radical resection who were screened based on microvascular invasion (MVI) and Ki-67 expression.Methods:Of 400 patients with hepatocellular carcinoma who underwent radical resection in the Affiliated Hospital of Qingdao University from January 2013 to December 2019 were included and analyzed retrospectively, including 324 males and 76 females, aged (59.7±9.8) years, ranging from 32 to 87 years. According to whether they received adjuvant TACE treatment after operation, they were divided into simple operation group ( n=210) and TACE + operation group ( n=190). The recurrence in the first year after operation was followed up by outpatient reexamination. Univariate and multivariate Cox regression analysis were used to analyze the influencing factors of recurrence free survival after surgical resection. Subgroup analysis was performed according to Ki-67 and MVI to compare the recurrence free survival. Results:Multivariate Cox regression analysis showed that patients with proportion of Ki-67 positive cells ≥27.5% ( HR=2.073, 95% CI: 1.433-3.000, P<0.001) and MVI positive ( HR=2.339, 95% CI: 1.584-3.456, P<0.001) had increased risk of recurrence after radical resection. The 1-year cumulative recurrence free survival rate in the simple operation group was 70.0%, and there was no significant difference compared with 67.9% in the operation + TACE group( χ 2=0.08, P=0.774). Subgroup analysis: in the low expression of Ki-67 combined with negative MVI group ( n=128), the cumulative recurrence free survival rate of one year after operation in the simple operation group ( n=84) was 91.7%, which was significantly higher than 72.7% in the operation + TACE group ( n=44)( χ 2=8.22, P=0.004). There was no significant difference in the 1-year cumulative recurrence free survival rate between the simple operation group and the operation + TACE group (both P>0.05) in patients of Ki-67 high expression combined with MVI negative or Ki-67 low expression combined with MVI positive. In the Ki-67 high expression combined with MVI positive group ( n=107), the cumulative one-year recurrence free survival rate in the simple operation group ( n=62) was 40.3%, which was significantly lower than 60.0% in the operation + TACE group ( n=45)(χ 2=4.22, P=0.040). Conclusion:High expression of Ki-67 (≥27.5%) combined with positive MVI are the prediction factors for postoperative TACE treatment. Low expression Ki-67 (<27.5%) combined with negative MVI was contraindicated for postoperative TACE treatment.

The use of whole exome sequencing (WES) for the detection of disease-causing variants of genetic diseases and for non-invasive prenatal screening (NIPS) of fetal aneuploidies are two major clinical applications of next generation sequencing (NGS). This article has summarized the official documents developed and updated by the American College of Medical Genetics and Genomics (ACMG) on governing WES and NIPS. These include the development of expert consensus policies and position statements on an ongoing basis to guide clinical application of NGS technology and variant analysis, establish evidence-based practical resources, as well as standards and guidelines to govern diagnosis and screening. These ACMG documents are valuable references to Chinese geneticists, but direct adoption of these standards and guidelines may not be practical due to the differences in disease-associated variant frequencies in Chinese population, socioeconomic status, and medical practice between the two countries. It is hoped that this review could facilitate the development of NGS and NIPS standards and guidelines that are consistent with international standards and concordant with medical genetics practice in China to provide high-quality, efficient and safe clinical services for patients and their families with genetic diseases.
China ; Consensus ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Technology ; United States

Objective:To explore the effects of miR-181a-5p on the occurrence and development of gastrointestinal stromal tumors (GIST) through targeting CTDSPL mediating TGF-β signaling pathway.Methods:Surgical treatment of GIST patients in the First People’s Hospital of Shangqiu City from Jan. 2016 to Dec. 2019 were selected as research objects, and tumor tissue and adjacent normal tissue were collected intraoperatively. The clinicopathological data of the patients were analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of CTDSPL gene and miR-181a-5p expression. Western blot was used to detect the protein level of CTDSPL and TGF-β signaling pathway related factors. Human gastrointestinal stromal tumor cell lines (GIST-T1) were transfected with miR-181a-5p mimic, miR-181a-5p inhibitor, or CTDSPL overexpression vector. MTT was used to detect cell proliferation activity, Transwell assay was utilized to detect cell invasion, flow cytometry was used to determine cell apoptosis in each group.Results:Compared with adjacent tissues, expression of miR-181a-5p and TGF-β signaling pathway related factors was activated while CTDSPL expression was inhibited. Tumor size, invasion depth and modified NIH grading were related to the mRNA expression level of CTDSPL gene in GIST tumor tissues (All P<0.05) . Compared with Blank group, inhibition of miR-181a-5p or CTDSPL overexpression had the ability to inhibit the cell viability and invasion, induce apoptosis. The effects of miR-181a-5p mimic on GIST-T1 can be saved by CTDSPL overexpression. Conclusion:miR-181a-5p can promote the occurrence and development of GIST by down-regulating the CTDSPL gene level and activating TGF-β signaling pathway.

Objective: To analyze the diagnostic value of ultrasound guided 14 gauge coreneedle biopsy (US-CNB) in breast nodules. Methods: We retrospectively analyzed the pathological results of US-CNB and surgical excision from 373 breast nodules in Peking University International Hospital from Sep 2016 to Nov 2018 to evaluate the accuracy of 14g US-CNB. Results: A total of 349 patients(373 nodules)underwent US-CNB. US-CNB reported 282 benign lesions(75.6%, 282/373), 20 high-risklesions(5.4%, 20/373), and 71 malignant lesions(19.0%, 71/373). For 282 CNB reported benign lesions, the surgical pathology confirmed 235 lesions , 46 for high-risk lesions and 1 for malignant lesion with a concordancy of 83.3%(235/282)and the underestimation rate was 16.7%(47/282). US-CNB identified 20 high-risk lesions. According to surgical results, 15 were high-risk lesions and 5 were malignant lesions with a concordancy of 75% (15/20)and the underestimation rate was 25%(5/20). When it comes to malignant lesions, the excision results showed that 70 were malignant lesions and 1was high-risk lesion with a concordancy of 98.6%(70/71)and the overestimation rate was 1.4%(1/71). The concordance of the histological type , calculated for 50 invasive carcinomas, was 92% (46/50) with a kappa value of 0.77.The concordance of the histological grade could be calculated for 38 invasive ductal carcinomas with the Elston-Elllis Method . It was 89.5% (34/38) with a kappa value of 0.57. Conclusions The pathology result of 14gUS-CNB is in good consistency with surgical excision for breast benign and malignant lesions.

Objective To discuss the clinical pathological features,diagnosis and differential diagnosis,therapy and prognosis of primary breast diffuse large B-cell lymphoma(PB-DLBCL).Methods The clinical manifestations,pathological features,immunophenotypic characteristics of 4 cases of PB-DLBCL were retrospectively reviewed,and related literatures were reviewed.Results All of the 4 patients were women,aged 45 to 69 years,with the median 58.5 years.There were 3 cases of lesions involving the left breast and 1 case of the right breast.Microscopic observation showed that the normal structure of the mammary gland was destroyed,and no capsule was seen.There was a large number of large-to medium-sized heterotypic lymphoid cells which characterized as diffuse infiltration between the remaining ducts or lobules of mammary gland.Tumor cells infiltrated adipose tissue,mainly as central blast-like cells (3 cases) and immunoblast-like cells (1 case).No lymphatic epithelial lesions were observed.The immunophenotype showed 4 cases were non-GCB type.Immunostaining showed that the neoplastic cells were LCA,CD20,CD79a and MUM-1 positive.Ki67 index were from 50％ to 80％.The follow-up time of these cases was until Dec.2017.There was one recurrence during the follow-up period.The patient died 13 months later.One patient was alive and had survived for 66 months.Two patients were lost to follow-up.Conclusions PB-DLBCL is extremely rare,mainly found in women.Most of the cell origin types are non-GCB type,which is often misdiagnosed as breast cancer.The diagnosis of PB-DLBCL is confirmed by pathological biopsy and immunohistochemical markers.The treatment is not clear,and a comprehensive treatment plan such as R-CHOP/ CHOP chemotherapy combined with radiotherapy is recommended.

Objective To analyze the influence factors of local efficacy by parametric contrast enhanced ultrasound (CEUS) of the hepatocellular carcinoma (HCC) patient treated with transcatheter arterial chemoembolization (TACE),and to investigate the application value of parametric CEUS in TACE.Methods From August 2011 to March 2014,a total of 61 HCC patients [60 men,1 women;age range:18-76 years,mean age:(53 ± 13)years old] who underwent one procedure of TACE were enrolled in this prospective study.All cases were scanned by CEUS 1-7 days before and after TACE (3 days,15 days and 30 days post-TACE).Analysis of tumor perfusion during the procedure of CEUS was performed with dedicated software (SonoLiver,TomTec,Germany and Bracco,Italy).Time-intensity curves were plotted and parameters were extracted.According to modified response evaluation criteria in solid tumors (mRECIST),we evaluated the response of TACE using contrast-enhanced computed tomography (CECT) and CEUS 30 days after TACE,which was as reference standard.Results There was a middle negative correlation between the reference standard and the PSV of the hepatic artery pre-TACE,and the correlation coefficient was 0.436 (P =0.011).There was a low negative correlation between the reference standard and the TTP of the reference region on 3 days post-TACE and the analysis region pre-TACE,and the correlation coefficient was -0.264 and-0.268 (P =0.047,P =0.037).Conclusions Our preliminary study suggests,some parameters of CEUS can predict the local response of TACE.

Objective To study the early survival rate and its influencing factors of extremely preterm infants and extremely low birth weight ( ELBW ) infants.Method All extremely preterm infants and/or ELBW infants in Shandong Provincial Hospital from January , 2010 to December 2015 were studied retrospectively.The factors affecting their survival rate and their complications were analyzed retrospectively . All cases were assigned into the survival group and the death group .On the other hand , they were also assigned into two groups according to their birth , pre-2014 and post-2014.Result A total of 142 extremely preterm infants and/or ELBW infants were enrolled, their gestational age was 28 (27, 29) weeks, birth weight was 925 (830, 965) g.76 cases (53.5%) survived, 66 cases (46.5%) died.Factors associated with the survival rate were early onset sepsis , placental abruption , perinatal asphyxia , birth weight and pulmonary hemorrhage (P<0.05).There were 67 cases pre-2014 in which 30 cases survived (44.8%), while 75 cases post-2014 in which 46 cases survived ( 61.3%) .Comparative analysis between the two groups pre-2014 and post-2014 revealed that the survival rate was significantly different (χ2 =3.900, P=0.048).The top 2 underlying causes of death before 2014 were perinatal asphyxia and early onset sepsis . Furthermore, early onset infection became the first cause of death after 2014.Conclusion Along with the prevalence of neonatal resuscitation program and the optimization of respiratory support strategies in premature infants , the early survival rate of extremely preterm infants and /or ELBW infants has improved significantly.However, early onset sepsis may have been the crucial cause for their perinatal mortality .