Therapeutic effect of retention enema with compound rhubarb decoction on a rat model of minimal hepatic encephalopathy based on bile acid metabolomics / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of rhubarb decoction （RD） retention enema on a rat model of minimal hepatic encephalopathy （MHE） and its mechanism of action based on bile acid （BA） metabolomics. MethodsA total of 55 male Sprague－Dawley rats were randomly divided into blank group （NC group with 10 rats）， hepatic encephalopathy group （HE group with 15 rats）， MHE group with 15 rats， and MHE+rhubarb decoction treatment group （MHEY group with 15 rats）. Intraperitoneal injection of carbon tetrachloride （CCl4） and thioacetamide （TAA） was performed to establish a rat model of MHE or HE， and the rats were sacrificed after 2 weeks of administration. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， total bilirubin （TBil）， and total bile acid （TBA） and the concentration of blood ammonia were measured； the colonic contents were collected to measure pH value； liver and brain tissue samples were collected， and HE staining was used to observe the histopathological changes of the liver； the bile was collected， and liquid chromatography－mass spectrometry was used to perform BA－targeted metabolomics analysis. Continuous data were expressed as mean±standard deviation； a one－way analysis of variance was used for comparison between multiple groups， and the least significant difference t－test was used for further comparison between two groups. ResultsCompared with the NC group， the HE group and the MHE group had a significant increase in searching platform latency （after modelling and after administration） and a significant reduction in the number of platform crossings （all P<0.05）； compared with the MHE group， the MHEY group had a significant reduction in searching platform latency （after administration） and a significant increase in the number of platform crossings， and the HE group had a significant increase in searching platform latency and a significant reduction in the number of platform crossings （all P<0.05）. Compared with the NC group， the HE group and the MHE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）； compared with the MHE group， the MHEY group had significant reductions in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）， and the HE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）. The MHE group had significantly lower TBA， primary BA， and secondary BA than the NC group （all P<0.05）； compared with the MHE group， the HE group had significantly lower TBA and primary BA （all P<0.05）， and the MHEY group had significantly higher TBA and primary BA （all P<0.05）. Compared with the NC group， the MHE group had significant reductions in GCDCA， GUDCA， GHDCA， TCDCA， TUDCA， GLCA， and TLCA （all P<0.05） and significant increases in γ－MCA， THCA， 7－KDCA， AlloLCA， and α－MCA （all P<0.05）， and compared with the MHE group， the MHEY group had significant increases in THDCA， TMCA， TCDCA， TUDCA， and TLCA （all P<0.05）. ConclusionRD retention enema can improve liver injury and cognitive function in a rat model of MHE induced by CCl4 and TAA by regulating the enterohepatic circulation of BA， possibly by increasing the synthesis of taurine－binding BA.

Analysis of the status and risk factors of in stent restenosis in patients with acute myocardial infarction and diabetes mellitus one year after percutaneous coronary intervention / 中国医师杂志

Objective:To analyze the status of in stent restenosis (ISR) in patients with acute myocardial infarction (AMI) and diabetes mellitus (DM) one year after percutaneous coronary intervention (PCI), and explore the risk factors.Methods:From December 2019 to December 2020, 158 patients with AMI and DM who were treated by PCI in Qionghai Hospital of Traditional Chinese Medicine and the First Affiliated Hospital of Hainan Medical College were selected. They were followed up for one year after surgery to calculate the incidence of ISR. The patients were divided into ISR group and non ISR group according to whether ISR occurred. The difference of clinical data between the two groups was compared. Logistic regression was used to analyze the risk factors for the occurrence of ISR in AMI patients with DM 1 year after PCI.Results:55 patients were followed up for 1 year, and the incidence of ISR was 34.81% (55/158). There were significant difference between ISR group and non ISR group in hypertension history, old myocardial infarction history, smoking, exercise ratio, preoperative low density lipoprotein cholesterol (LDL-C), total bilirubin (TBIL), blood uric acid (UA), plasma fibrinogen (FIB), glycosylated hemoglobin (HbA 1c) levels, coronary artery lesion number, stenosis degree, stent length, stent diameter (all P<0.05). Multivariate logistic regression analysis showed that hypertension history, smoking, LDL-C, FIB, HbA 1c and stent length were independent risk factors for ISR in AMI patients with DM after PCI, and exercise and appropriate increase of stent diameter were protective factors (all P<0.05). Conclusions:The incidence of ISR in AMI patients with DM at 1 year after PCI is relatively high, and its occurrence is related to many factors. In order to reduce the risk of ISR after PCI, we should encourage smoking cessation, exercise, strengthen the monitoring of biochemical indicators, and appropriately increase the diameter of stent during PCI.

Research on the regulation of food therapy prescription of Traditional Chinese medicine in treating children′s stagnation based on data mining / 中国实用护理杂志

Objective:Data mining technology was used to analyze the regulation of food therapy prescriptions in treating children′s stagnation.Methods:Collect the therapy prescriptions used for regulating children's stagnation in the Dictionary of Traditional Chinese Medicine Prescriptions, the Complete Record of Dietary Therapy Prescriptions of Traditional Chinese Medicine and the Dictionary of Chinese Medicinal Diet, extract the information of prescription name, composition, etc, and use SPSS 22.0 for frequency analysis, and use Weka for correlation analysis. Results:A total of 99 dietary prescriptions for children with hysteria were included, involving a total of 62 foods, with a total use frequency of 224 times, among which the food with high use frequency were chicken gizzard, japonica rice, hawthorn, etc. The four characteristics of food were mainly concentrated in the flat, the five tastes were mainly concentrated in the sweet, the return channel was mainly concentrated in the spleen and stomach channel, and the effect was mainly concentrated in the absorption of food and tonic deficiency. The main symptoms of the therapeutic prescription for children's accumulation of stagnation were internal accumulation of milk and food and combination of spleen deficiency. The commonly used food combination for children's accumulation of stagnation of milk and food was "fructus amomi - chicken gizzard". The commonly used food combination of children with spleen deficiency and accumulation of stagnation was "lentil bean-yam-japonica rice" and "millet-yam".Conclusions:Traditional Chinese medicine diet prescription for the treatment of children's accumulation of stagnation pay attention to harmony and regulation, sweet and slow tonifying, emphasizing the adjustment of the spleen and stomach, taking into account the regulation of lung, following the "eliminating and supplementing both, according to the cause of treatment" rule, advocate syndrome differentiation of food.

Causes of HLA-A2 reactive antibodies and analysis of their eplets / 中国输血杂志

【Objective】 To analyze differences of eplets between the patient who generated HLA allele-specific antibodies after platelet transfusion with donors. 【Methods】 The HLA genotypes of the patient and donors were detected by PCR-SBT, and the Luminex single antigen beads coating was used to screen HLA-Ⅰ antibodies in the patient’s serum. HLA Matchmaker was utilized to analyze different amino acids and eplets. 【Results】 The patient carried HLA-A*02∶03 allele, and HLA-A2 antibodies were found in his serum after platelet transfusion (A*02∶01, A*02∶06, and A*02∶07). Sequence alignment showed that the patient′s A*02∶03 has a difference in position 149, which resulted in a different eplet between A*02∶03 and A*02∶01, A*02∶06, A*02∶07 and then induced the production of antibodies. 【Conclusion】 HLA antibodies are specific for HLA epitopes that have structural differences due to amino acid differences between HLA alleles, suggesting that high-resolution typing of HLA-A, -B need to be conducted in patients and donors, and the acceptable mismatch of HLA should be determined based on epitopes rather than antigens, so as to reduce alloimmune response and improve platelet count after transfusion.

Mining intrinsic information of convalescent patients after suffering coronavirus disease 2019 in Wuhan.

OBJECTIVE: To summarize the potential characteristics of convalescent patients with coronavirus disease 2019 (COVID-19) in China based on emerging clinical tongue data and guide the treatment and recovery of COVID-19 patients from the perspective of Traditional Chinese Medicine tongue diagnosis. METHODS: In this study, we developed and validated radiomics-based and lab-based methods as a novel approach to provide individualized pretreatment evaluation by analyzing different features to mine the orderliness behind tongue data of convalescent patients. In addition, this study analyzed the tongue features of convalescent patients from clinical tongue qualitative values, including thick and thin, fur, peeling, fat and lean, tooth marks and cracked, and greasy and putrid fur. RESULTS: We included 2164 tongue images in total (34% from day 0, 35.4% from day 14 and 30.6% from day 28) from convalescent patients. The significance results are shown as follows. Firstly, as the recovery time prolongs, the L average values of tongue and coat decrease from 60.21 to 57.18 and from 60.06 to 57.03 respectively. Secondly, the decrease of abnormality rate of tongue coat, included greasy tongue fur, putrid fur, teeth-mark, thick-thin fur, are of significant statistical difference ( < 0.05). Thirdly, the average value of gray-level co-occurrence matrices increases from 0.173 to 0.194, the average value of entropy increases from 0.606 to 0.665, the average value of inverse difference normalized decrease from 0.981 to 0.979, and the average value of dissimilarity decrease from 0.1576 to 0.1828. The details of other radiomics features are describe in results section. CONCLUSIONS: Our experiment shows that patients in different recovery periods have a relationship with quantitative values of tongue images, including L color space of the tongue and coat radiomics features analysis. This relationship can help clinical doctors master the recovery and health of patients as soon as possible and improve their understanding of the potential mechanisms underlying the dynamic changes and mechanisms underlying COVID-19.

Bie Jia Jian pill enhances the amelioration of bone mesenchymal stem cells on hepatocellular carcinoma progression.

BACKGROUND: The therapeutic efficiency of Traditional Chinese Medicine (TCM) in suppressing the recurrence and metastasis of hepatocellular carcinoma (HCC) has been well proved. OBJECTIVE: The aim of this study is to investigate the role of Bie Jia Jian pill (BJJP) combined with bone mesenchymal stem cells (BMSCs) in HCC progression. METHODS: Flow cytometry was used to identify BMSCs isolated from BALB/c mice. The expressions of biomarkers and apoptosis rate of cancer stem cells (CSCs) enriched from Huh7 cells were also measured. The osteogenic differentiation and adipogenic differentiation ability of isolated BMSCs was determined by oil red O staining and Alizarin Red Staining. CSCs were used to establish the orthotopic HCC model. Histological changes in the liver tissues were examined by hematoxylin-eosin (H&E) staining and Van Gieson (VG) staining. The cell apoptotic rate in the cancer tissues was detected by TUNEL staining. The cell proliferation antigen Ki67 in the cancer tissues were detected by immunofluorescence assay and PCR, respectively. The levels of CSCs cellular surface markers (CD24, CD133 and EpCAM) and Wnt/ß-catenin signal pathway related proteins were detected by PCR and western blot. RESULTS: Treatment of BJJP or BMSCs both improved the morphology induced by HCC and suppressed the differentiation ability of CSCs, as evidenced by down-regulated expressions of CD24, CD133, EpCAM and Ki67. The protective effect of BJJP or BMSCs in cancer tissues can be enhanced by the combination of BJJP and BMSCs. In addition to that, BJJP or BMSCs alone was found to increase the expression of miR-140 and promote cell apoptosis in CSCs, while down-regulation of miR-140 partially reversed the protective effect of BMSCs or BJJP + BMSCs on cancer tissues. BJJP + BMSCs treatment together also can down-regulate the expressions of Wnt3a and ß-catenin. CONCLUSIONS: These results proved the inhibitory role of BJJP + BMSCs in HCC development through regulating miR-140 and Wnt/ß-catenin signal pathway.

Clinical risk factors for fracture risk prediction in patients with type 2 diabetes using adjusted FRAX / 中华内分泌外科杂志

Objective:To study the clinical risk factors for osteoporotic fracture (OF) risk prediction in patients with type 2 diabetes mellitus (T2DM) using adjusted fracture risk assessment tool (FRAX) .Methods:A cross-sectional study of 429 patients with T2DM who were hospitalized in the Department of Endocrinology and Geriatrics of the Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University from Sep. 2019 to Sep. 2020 was conducted. Participants were divided into OF low-risk group and OF high-risk group. Participant characteristics (age, gender, height, weight, waist, blood pressure, history of drug treatment, serum glucose, glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) , high-density lipoprotein cholesterol (HDL-C) , triglyceride, serum uric acid, alkaline phosphatase, and thyroid stimulating hormone levels, urine protein/creatinine ratio, urea, creatinine and TPOAB) and dual energy x-ray absorptiometry results were obtained and analyzed. Logistic regression model was used to investigate the relationship between the OF risk of T2DM assessed by adjusted FRAX and clinical risk factors.Results:Patients in the OF high-risk group accounted for 9.09% of the subjects. After adjustment for other variables, the duration of diabetes was still positively associated with significantly elevated risk of OF assessed by adjusted FRAX ( OR 7.660, 95% CI 1.661-35.334, P=0.009) , whereas the blood uric acid was negatively associated with significantly elevated risk of OF assessed by adjusted FRAX ( OR 0.345, 95 % CI 0.128-0.928, P=0.035) .Likewise, LDL-C levels decreased the odds of the risk of OF assessed by adjusted FRAX ( OR 0.316, 95 % CI 0.114-0.881, P=0.028) . There was no significant relationship between alkaline phosphatase ( OR 1.902, 95 % CI 0.904-4.004, P=0.090) as well as total cholesterol ( OR 0.297, 95% CI 0.056~1.560, P=0.151) levels and the elevated risk of OF assessed by adjusted FRAX. Conclusion:Diabetes duration could be a risk factor for OF risk prediction in patients with T2DM using adjusted FRAX, and serum uric acid and LDL-C could be protective factors for OF risk prediction in patients with T2DM using adjusted FRAX.

Pathogenic bacteria distribution and antimicrobial resistance in children aged 0 to 14 years with urinary tract infections in a single center in Shanghai / 中华传染病杂志

Objective:To investigate the distribution and antimicrobial resistance patterns of common pathogens in children with urinary tract infections in a single center in Shanghai, and to provide basis for the selection of empirical antibiotics in the clinical practice.Methods:The clinical data, urine culture and drug sensitivity tests results of children with urinary tract infections between 0 to 14 years admitted to the Children′s Hospital of Fudan University from January 2016 to December 2019 were retrospectively analyzed. According to the time of onset and the complicated factors, the patients were divided into different groups. The distributions and antimicrobial resistance patterns of common pathogens were compared among the groups. The chi-square test was used for statistical analysis.Results:Among the 1 832 children, 1 042 cases had positive urine culture, with the culture positive rate of 56.9%. The top five pathogens detected were Escherichia coli (375 strains, 36.0%), Enterococcus faecium (164 strains, 15.7%), Klebsiella pneumoniae (133 strains, 12.8%), Enterococcus faecalis (95 strains, 9.1%) and Pseudomonas aeruginosa (44 strains, 4.2%). The annual detection rates of gram-negative bacteria (65.3% to 72.9%) were always higher than those of gram-positive bacteria (22.6% to 30.1%). The distributions of pathogens among the years were not significantly different ( χ2 =27.79, P=0.146). In patients with complicated urinary tract infections, the detection rates of Pseudomonas aeruginosa (5.8%(40/688) vs 1.1%(4/354)) and fungi (6.5%(45/688) vs 1.7%(6/354)) were significantly higher than those in patients with simple urinary tract infections ( χ2=12.68 and 11.79, respectively, both P<0.050). Both of Escherichia coli and Klebsiella pneumoniae had the highest resistance rates to ampicillin, which were 87.2%(301/345) and 87.1%(115/132), respectively. The resistance rates of Escherichia coli to amikacin, nitrofurantoin, fosfomycin, cefmetazole, piperacillin/tazobactam, ertapenem, imipenem and meropenem were 1.4%(5/345), 6.1%(21/345), 6.1%(21/345), 8.3%(11/132), 11.6%(40/345), 6.4%(22/345), 4.6%(16/345) and 4.6%(16/345), respectively. The resistance rates of Klebsiella pneumoniae to these drugs were 6.1%(8/132), 37.9%(50/132), 15.2%(20/132), 23.2%(13/56), 26.5%(35/132), 23.5%(31/132), 17.4%(23/132) and 16.7%(22/132), respectively, which were all higher than those of Escherichia coli, and the differences were all statistically significant ( χ2=6.02, 76.17, 9.99, 7.94, 16.04, 28.29, 20.79 and 18.84, respectively, all P<0.050). The resistance rates of Pseudomonas aeruginosa to cefoperazone/sulbactam, piperacillin/tazobactam and ceftazidime were 6.8%(3/44), 4.5%(2/44) and 2.3%(1/44), respectively, while those to carbapenems, amikacin and ciprofloxacin were all 0(0/44). The resistance rate of Enterococcus faecium to ampicillin was 96.8%(153/158), while that of Enterococcus faecalis was 9.1%(8/88). There was no Enterococcus strain resistant to vancomycin, teicoplanin or linezolid. When dynamically comparing the trends of the antimicrobial resistance from 2016 to 2019, the resistance rates of Escherichia coli and Klebsiella pneumoniae to β-lactams (including carbapenems) antimicrobial agents had shown a downward trend. Conclusions:Gram-negative bacteria are still the main pathogens of urinary tract infections in children, with a downward trend of drug resistance rates to β-lactams (including carbapenems) antimicrobial agents.

The effects of Shexiang Baoxin pills combined with intracoronary injection of nicorandil on myocardial blood perfusion and short-term prognosis for STEMI patients after PPCI / 药学实践杂志

Objective To observe the effects of Shexiang Baoxin pill combined with intracoronary injection of nicorandil on myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Methods 151 patients with acute myocardial infarction after PPCI were enrolled in this study. Those patients were admitted to our hospital during January 2017 to January 2018. According to the numerical randomization method, 51 patients were selected as routine treatment group (group A), 50 patients with intracoronary injection of nicorandil (group B) and 50 patients received intracoronary injection of nicorandil plus oral Shexiang Baoxin pills (group C). Intra-operative corrected TIMI frame count (cTFC), postoperative TIMI grade 3 blood flow ratio, 2-hour ECG ST segment fallback >50% index, the incidence of major adverse cardiovascular events (MACE) during hospitalization and the incidence of angina and MACE within 3 months after surgery were evaluated. Results cTFC, 2 hours postoperative ECG ST segment fall >50% index in group B and C were better than group A (P<0.05). The results from group C were better than group B. Group C exhibited better results than group B and C in post-operative angina pectoris 3 months after surgery (P<0.05). Conclusion Shexiang Baoxin pills combined with intra-coronary injection of nicorandil can improve myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction

A single-center retrospective analysis of surgical strategy and clinical outcome of pulmonary nodules using pulmonary subsegments as anatomical unit / 中国胸心血管外科临床杂志

@#Objective    To analyze the results and rationality of the lesion-focused strategy with subsegment as the pulmonary anatomical unit for pulmonary nodules with a diameter of ≤2 cm which require surgery. Methods    Clinical data of 246 patients with pulmonary nodules who underwent surgery in the Department of Thoracic Surgery of The First Affiliated Hospital of Nanjing Medical University from January 2017 to October 2018 were retrospectively analyzed, including 76 males and 170 females, with an average age of 53.30±11.82 years. The patients were divided into four groups, a single segmentectomy group, a segmentectomy combined with adjacent subsegmentectomy group, a single subsegmentectomy group and a combined subsegmentectomy group, according to the different surgical approaches, to compare preoperative, intraoperative, and postoperative related data. Results    There was no perioperative death. Among the four groups, there was no statistical difference in gender (P=0.163), age (P=0.691), diameter of the nodule (P=0.743), longitudinal position of the nodule (depth ratio, P=0.831), postoperative pulmonary leakage (P=0.752), intraoperative blood loss (P=0.135), pathological type (P=0.951) or TNM stage (P=0.995); there were statistical differences in transverse position of the nodule (P<0.001) and number of subsegments involved (P<0.001). The results of multivariate logistic regression analysis showed that compared with combined subsegmentectomy, the odds ratio (OR) of the lung nodule in segmentectomy combined with adjacent subsegmentectomy as intersegment nodules was 5.759 (95%CI 1.162 to 28.539, P=0.032). Conclusion     The surgical strategy of lesion  focused and subsegment as anatomical unit is safe and feasible for surgical treatment of pulmonary nodules with diameter ≤2 cm. The transverse position of the nodules is an important factor affecting the choice of surgical method for the middle and lateral nodules with a diameter of ≤2 cm, and the longitudinal location of the nodule is not an influencing factor. For nodules in inner zone, the diameter also is one of the factors influencing the choice of surgical method.

Research Status of Tumor-associated Fibroblasts Regulating Immune Cells / 中国肺癌杂志

Cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells are the most essential components of the tumor microenvironment (TME). They communicate with each other in tumor microenvironment and play a critical role in tumorigenesis and development. CAFs are very heterogeneous and different subtypes of CAFs display different functions. At the same time, it can contribute to the regulation of the function of tumor-infiltrating immune cells and eventually result in the carcinogenesis, tumor progression, invasion, metastasis and other biological behaviors of tumors by producting various growth factors and cytokines etc. Based on the current research results at home and abroad, this paper reviews the recent research progress on the regulation of CAFs on infiltrating immune cells in tumor microenvironment.
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Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus displayed remarkable efficacy against authentic B.1.351 virus. Each of these 3 mAbs in combination with one neutralizing Ab recognizing non-competing epitope exhibited synergistic effect against authentic SARS-CoV-2 virus. Surprisingly, structural analysis revealed that 58G6 and 13G9, encoded by the IGHV1-58 and the IGKV3-20 germline genes, both recognized the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly bound to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrated prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. These 2 ultrapotent neutralizing Abs can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.

Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells.

BACKGROUND AND OBJECTIVES: Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. METHODS AND RESULTS: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/ß-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of ß-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability. Downregualted expressions of Wnt/ß-catenin signal pathway related proteins, Wnt3a and ß-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and ß-catenin as well as the cell viability and apoptosis of CSCs. Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. CONCLUSIONS: Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/ß-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 (

Human epidermal growth factor receptor 2-positive metastatic breast cancer with novel epidermal growth factor receptor -ZNF880 fusion and epidermal growth factor receptor E114K mutations effectively treated with pyrotinib: A case report.

INTRODUCTION: In about 15% to 20% of breast cancer cases, human epidermal growth factor receptor 2 (HER2) over-expression or gene-amplification is associated with poor prognosis. Thanks to the development of target therapies, HER2 positive patients can be managed using HER2-targeting drugs. There are several kinds ofHER2 inhibitors, such as trastuzumab, lapatinib, and pyrotinib. Pyrotinib which exert different functions, of note, the latest generation of the drug, is an irreversible small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) (HER1) and/or HER2 and/or HER4. Both lapatinib and pyrotinib potentially target EGFR and/or HER2, but in some instances, induces different responses of patients with EGFR and/or HER2 mutations. This is attributed to the different mutations in EGFR and HER2 genes, which may form distinct types of HER2 dimers, with different binding capacities to drugs. PATIENT CONCERNS: Five years ago, a patient underwent a radical mastectomy in an external hospital. Results of the resection histopathology revealed an invasive ductal carcinoma, pT3N0M0, stage IIB, HER2 positive. The lady patient received 6 cycles of adjuvant chemotherapy and was subjected to adjuvant trastuzumab therapy for 1 year. After a regular 1-year follow-up and in March 2018, she complained of chest pain and visited our hospital. We diagnosed her with metastatic breast cancer, positive for HER2. DIAGNOSIS: positron emission tomography/computed tomography showed multiple metastases in the lung and sternum, while the breast lesions did not progress, the curative effect of which we evaluated as a progressive disease. Then, lapatinib integrated with chemotherapy was administered to the patient. After 5 cycles of the treatment, the patient experienced lower back pain. Through CT examination, it was revealed that she had multiple metastases in the lung and sternum, in addition to new metastases in the lumbar spine and right lobe of the liver. Moreover, magnetic resonance imaging revealed multiple metastases in the brain, and the disease further progressed. The results of circulating tumor DNA assays showed that other than HER2 amplification, novel EGFR-ZNF880 fusion and EGFR E114K mutations developed. INTERVENTIONS: The patient was administered with a combination of pyrotinib with chemotherapy. OUTCOMES: After 2 months of pyrotinib treatment, the metastases of the lung, sternum, lumbar spine, and right lobe of the liver disappeared. Also, the size of the brain metastases reduced while bone metastases were relieved. The curative effect was evaluated as a partial response. Following the results of circulating tumor DNA assays, HER2 amplification, EGFR-ZNF880 fusion, and EGFR E114K mutations disappeared. However, since a small lesion was present in the brain, the patient was subjected to radiotherapy in the head. Notably, after 9 months treatment with pyrotinib, enhanced CT indicated that tumors in the breast, liver, both lungs, brain, and bone were under control. The patient continually received oral pyrotinib, however, a new brain lesion appeared 6 months later. Overall, we managed to regulate the efficacy of pyrotinib for up to 15 months. CONCLUSION: This case report demonstrates that EGFR-ZNF880 fusion and EGFR E114K mutations may contribute or lead to the formation of a special HER2 dimer, which is rapidly resistant to lapatinib but sensitive to pyrotinib. Of note, this is the first report that such a new fusion has been found.

Identification of Cross-Reactive CD8+ T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants

Despite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369 (KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369 mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369 epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.

A key linear epitope for a potent neutralizing antibody to SARS-CoV-2 S-RBD

The spread of SARS-CoV-2 confers a serious threat to the public health without effective intervention strategies1-3. Its variant carrying mutated Spike (S) protein D614G (SD614G) has become the most prevalent form in the current global pandemic4,5. We have identified a large panel of potential neutralizing antibodies (NAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 S6. Here, we focused on the top 20 potential NAbs for the mechanism study. Of them, the top 4 NAbs could individually neutralize both authentic SARS-CoV-2 and SD614G pseudovirus efficiently. Our epitope mapping revealed that 16/20 potent NAbs overlapped the same steric epitope. Excitingly, we found that one of these potent NAbs (58G6) exclusively bound to a linear epitope on S-RBD (termed as 58G6e), and the interaction of 58G6e and the recombinant ACE2 could be blocked by 58G6. We confirmed that 58G6e represented a key site of vulnerability on S-RBD and it could positively react with COVID-19 convalescent patients plasma. We are the first, as far as we know, to provide direct evidences of a linear epitope that can be recognized by a potent NAb against SARS-CoV-2 S-RBD. This study paves the way for the applications of these NAbs and the potential safe and effective vaccine design.

A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

Neutralizing antibodies (Abs) have been considered as promising therapeutics for the prevention and treatment of pathogens. After the outbreak of COVID-19, potent neutralizing Abs to SARS-CoV-2 were promptly developed, and a few of those neutralizing Abs are being tested in clinical studies. However, there were few methodologies detailly reported on how to rapidly and efficiently generate neutralizing Abs of interest. Here, we present a strategically optimized method for precisive screening of neutralizing monoclonal antibodies (mAbs), which enabled us to identify SARS-CoV-2 receptor-binding domain (RBD) specific Abs within 4 days, followed by another 2 days for neutralization activity evaluation. By applying the screening system, we obtained 198 Abs against the RBD of SARS-CoV-2. Excitingly, we found that approximately 50% (96/198) of them were candidate neutralizing Abs in a preliminary screening of SARS-CoV-2 pseudovirus and 20 of these 96 neutralizing Abs were confirmed with high potency. Furthermore, 2 mAbs with the highest neutralizing potency were identified to block authentic SARS-CoV-2 with the half-maximal inhibitory concentration (IC50) at concentrations of 9.88 ng/ml and 11.13 ng/ml. In this report, we demonstrated that the optimized neutralizing Abs screening system is useful for the rapid and efficient discovery of potent neutralizing Abs against SARS-CoV-2. Our study provides a methodology for the generation of preventive and therapeutic antibody drugs for emerging infectious diseases.

Impact of interstitial lung disease on postoperative morbidity and 60 day mortality after pulmonary resection for lung cancer / 中华胸心血管外科杂志

Objective:To evaluate the effect of interstitial lung disease(ILD) on postoperative morbidity and mortality in pulmonary resection for lung cancer patients.Methods:We retrospectively analyzed 971 patients undergoing pulmonary operation from January 2010 to January 2018 in our hospital. Clinical data including age, sex, history of chronic obstructive pulmonary disease(COPD), smoking history, smoking index, American Society of Anesthesiologists(ASA) classification, forced expiratory volume in 1 s(FEV1) % predict, surgical procedure, video assisted thoracoscopic surgery(VATS) or not, intraoperative blood transfusion, anesthesia time, operation time/one-lung ventilation time, blood loss, histology, postoperative morbidity, 60-days mortality, onset of acute exacerbation of interstitial lung disease(AE-ILD), drainage, extubation time, and postoperative stay were collected and analyzed.Results:There were 80(8.2%) and 891(91.8%) patients in ILD and non-ILD group, respectively. AE-ILD occurred in 5 patients, with a 60-day mortality of 80%. A multivariate regression analysis identified that the sex( P=0.023), ILD( P=0.001), COPD( P=0.027) were independent risk factors for postoperative morbidity. ILD( P=0.023) and postoperative morbidity( P=0.001) were independent risk factors for 60-day mortality in multivariate analysis. Conclusion:Patients with ILD had a higher incidence of postoperative morbidity and 60-day mortality. Based on the obvious postoperative morbidity and mortality, special attention and management should be taken in ILD patients.

Approach to the patient with lymphocytic hypophysitis during postpartum who presented with pituitary crisis / 中华内分泌代谢杂志

Lymphocytic hypophysitis(LYH) is a rare autoimmune inflammatory disorder of the pituitary gland, usually affecting young women in late pregnancy or postpartum period. To enhance the knowledge of LYH, herein we reported a case of LYH in a female during postpartum who presented with pituitary crisis.