The Expression and Clinical Significance of Fas and FasL in Lung Cancer

Objective: To investigate the expression and clinical significance of Fas andFasL in lung cancer. Methods: SP immunohistochemical technique was used to detect the expression ofFas and FasL in 46 cases of lung cancer and 30 cases of adjacent non-neoplastic tissue. Results:Down-regulation, of Fas and up-regulation of FasL were found in lung carcinoma. The levels of Fasexpression in squamous cell carcinoma, adenocarcinoma and SCLC were significantly lower than that ofadjacent normal tissues (P<0. 01) , while the expression levels of FasL were the opposite (P< 0.05). Fas expression was associated with high histological grade and no metastasis (P<0. 05). FasLexpression was related to histological grade, late clinical stage and metastasis (P<0. 05). BothFas and FasL expression was not related to the histological type of lung cancer (P>0. 05). Thelevel of Fas expression was negatively related to that of FasL (P<0. 05). Conclusion:Down-regulation of Fas and up-regulation of FasL may work in coordination with the occurrence,development and metastasis of lung cancer. Fas or FasL can be used as one of markers in earlydiagnosis of lung cancer. Therefore, the combined assay may be helpful in predicting the grade ofmalignancy and the prognosis of patients with lung cancer.

A meta-analysis of soluble suppression of tumorigenicity 2 （sST2） and clinical outcomes in pulmonary hypertension

Suppression of Tumorigenicity 2 （ST2） is a member of the interleukin （IL）-1 receptor family The ST2 receptor exists in two isoforms - ST2 ligand （ST2L） and soluble ST2 （sST2）.ST2L is a membrane receptor and sST2 is a trun- cated receptor which is soluble in the blood, allowing it to be detected in serum. IL-33 is a member of the IL-1 family of ligand and is the fimctional ligand of ST2L receptor. It binds to the ST2L, thereby mediating its immune function.

Assays for predicting and monitoring responses to lung cancer immunotherapy

Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer （NSCLC）. Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry （IHC） with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-I/PD-L1 pathway.

Advances in immunotherapy for treatment of lung cancer

Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-- with its capacity for memory, exquisite specificity and central and universal role in human biology--immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

Helicobacter pyloriseroprevalence in patients with lung cancer

AIM:To assess Helicobacter pylori(Hpylon)seroprevalence in a cohort of Greek patients with lung cancer. METHODS:Seventy-two lung cancer patients(55 males and 17 females,aged 58.2±11.7 years)and 68,age and gender-matched,control subjects were enrolled.All subjects underwent an enzyme-linked immunosorbent assay IgG serologic test for Hpylori diagnosis. RESULTS:A correlation between age and HpyloriIgG level was detected for both lung cancer patients(r=0.42, P=0.004)and controls(r=0.44,P=0.004).Seropositivity for Hpyloridid not differ significantly between patients with lung cancer and controls(61.1% vs 55.9%,P>0.05). Concerning the mean serum concentration of IgG antibodies against Hpylori,no significant difference between the two groups was detected(32.6±19.1 vs 27.4±18.3 U/mL, P>0.05). CONCLUSION:No significant association between Hpylori infection and lung cancer was found.

Immunomodulatory effect of pachymaran on cyclosporine A(CsA)-induced lung injury in mice

Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A(CsA)-induced lung injury in mice.Methods(i) Fifty male BALB/c mice were randomly divided into five groups(10 mice in each group): normal control(NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide(LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline(PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin(HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin(IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay(ELISA), and those of surfactant protein D(SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry(IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase(MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction(q RT-PCR).(ii) Another 60 BALB/c mice were divided into six groups(10 mice in each group) : NC group,model control(MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinicpolycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection.Detection methods were identical to those described in(i) above.Results(i) CsA(30 mg/kg) increased the lung index of mice(P < 0.001), and decreased the spleen index(P < 0.01), thymus index(P < 0.05), and the serum level of IL-2(P < 0.05). CsA(45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2(P < 0.01) in mice, and increased the serum level of IL-1β(P < 0.05) and the protein level of lung SP-D(P <0.001). CsA(60 mg/kg) increased the lung index of mice(P < 0.01), the serum level of IL-1β(P < 0.05), the protein level of lung SP-D(P < 0.01), and the mRNA levels of lung MPO and SP-D( P < 0.05), and decreased the thymus index of mice(P < 0.01). HE staining showed that 30, 45, and60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice.(ii) After pachymaran intervention in MC mice, the spleen and thymus indexes(P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased(P < 0.05).Moreover, 50 mg/kg pachymaran increased the thymus index(P < 0.05) and decreased the lung index(P < 0.01) in MC group. Pachymaran(50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β(P < 0.001), and the mRNA levels of MPO and SPD in lung tissues(P < 0.05) of mice. Pachymaran(100 mg/kg) increased the protein level of lung IL-2(P < 0.01), decreased the protein level of lung SP-D(P < 0.01), and the mRNA level of IL-1β(P < 0.001) in the lung tissues of mice. Pachymaran(200 mg/kg) increased the serum level of IL-2(P < 0.01) and lung IL-6 of mice(P < 0.05). Pachymaran(50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice(P < 0.05).Conclusion While the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.

Changes of the gastric endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma: An immunohistochemical quantitative study

AIM: The regional distributions and relative frequencies of some gastric endocrine cells of C57BL/6 mice were studied by immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon and human pancreatic polypeptide (HPP) after subcutaneous implantation of murine lung carcinoma (3LL) cells. METHODS: The experimental animals were divided into two groups, one is non-implanted sham and the other is 3LL-implanted group. Samples were collected from the two regions of stomach (fundus and pylorus) at 28 d after implantation of 3LL cells (1x105 cell/mouse). RESULTS: In this study, all the seven types of immunoreactive (IR) cells were identified except for HPP. Most of these IR cells in the gastric portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found occasionally. The regional distributions of gastric endocrine cells in the 3LL-implanted group were similar to those of non-implanted sham. However, significant decreases of some types of IR cells were detected in 3LL-implanted group compared to those of non-implanted sham. In addition, the IR cells showing degranulation were numerously detected in 3LL-implanted group. CGA-, serotonin- and somatostatin-IR cells in the fundus and pylorus regions, and gastrin-IR cells in the pylorus regions of 3LL-implanted groups significantly decreased compared to those of non-implanted sham. However, no changes on frequencies of CCK-8- and glucagon-IR cells were demonstrated between 3LL-implanted and non-implanted groups. CONCLUSION: Endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. Implantation of tumor cell mass (3LL) induced severe quantitative changes of gastric endocrine cell density, and the abnormality in density of gastric endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

Discussion on Etiology and Pathogenesis of Corona Virus Disease 2019 from“Cold-dampness and Insidious Dryness”

Based on the characteristics of the epidemic situation and the authors’understanding of the related ancient books and documents,this paper explores the etiology and pathogenesis of Corona Virus Disease 2019(COVID-19)from 5 aspects:abnormal climate in"warm winter",unique geographical location,pathogenesis evolution of cold and dampness mixed with insidious dryness,transmission and change of"triple energizer"of toxic pathogens,and game between healthy Qi and toxic pathogens.Combined with the special treatment of traditional Chinese medicine(TCM),the purpose is to make a modest contribution to curbing the epidemic situation with TCM.

Effects of Tai Chi Chuan training on cellular immunity in post-surgical non-small cell lung cancer survivors:A randomized pilot trial

Background： Although emerging evidence points to benefits from Tai Chi Chuan （TCC） in improving immune system function, its effects on cellular immune responses remain under-studied. The objective of this study was to evaluate the effects of TCC training on cellular immunity in non-small cell lung cancer patients. Methods： A 2-group randomized trial design in which post-surgical, non-small cell lung cancer survivors were randomly assigned to a TCC training group （n = 16） or a control group （n = 16）. The participants in the TCC group completed a 16-week intervention. The main immune response outcome measures assayed included the ratio of T-helper cells/T-suppressor cells （CD4＋：CD8＋ ratio） and complement regulatory proteins status （CRPs; CD55 and CD59）. Using repeated measures ANOVA, the data were analyzed for the participants who completed the study （n = 27）. Results： At 16 weeks, the TCC participants showed a significantly lower increment in the expression of CD55 （p 〈 0.05） as compared to the control group. No significant between-group differences were found in the CD4＋：CD8＋ ratio or CD59 expression. There were also no significant correlations among the changes in CRPs or T lymphocyte subpopulations, either. Conclusion： A 16-week TCC intervention caused no alterations in CD4＋：CD8＋ ratio, but significantly attenuated CD55 expression among post- surgical non-small cell lung cancer survivors.

The expression of Elf-1 and Ki-67 and their correlations in non-small-cell lung cancer

Objective: Elf-1 is a member of the proto-oncogenes Ets-related transcription factor family and over-expressed in many human tumors, Ki-67 is an important nuclear antigen associated with cell proliferation. This study investigated the expression of Elf-1 and Ki-67 in non-small-cell lung cancer(NSCLC) and studied their correlation with the clinicopathological features. Methods: Tissue microarray from 64 cases lung cancer tissue and 10 cases normal lung tissue was constructed, immunohistochemical method was used to evaluate the protein expressions of Elf-1 and Ki-67, correlations of the expression of Elf-1 and Ki-67 to clinicopathological features of NSCLC were analyzed. Results: Expression of Elf-1 and Ki-67 in NSCLC tissues were significantly higher than in normal lung tissues(P < 0.05), the positive rate of Elf-1 and Ki-67 was 73.44% and 64.06% in NSCLC group, Overexpression of Elf-1 in NSCLC was significantly related to histopathological grading, different clinical staging and the intensity of ELF-1 expression was significantly higher in the group with lymph node metastasis than that without(P < 0.05). Overexpression of Ki-67 was also closely related to tumor differentiation, clinical stages and lymph node metastasis(P < 0.05). In addition positive correlation was found between the expressive intensity of Elf-1 and Ki-67(τ = 0.295, P = 0.018). Conclusion: The high expression and positive correlation of Elf-1 and Ki-67 in NSCLC suggest that they probably play a role in onset and progression of lung cancer, united detecting their expression could be used as an valuable molecular biological index for predicting the malignant behavior and early diagnosis of NSCLC.

Changes of the intestinal endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma (3LL): An immunohistochemical quantitative study

AIM: To study the distributions and frequencies of intestinal endocrine cells in the C57BL/6 mouse with immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin,somatostatin, glucagons, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP) after abdominal subcutaneous implantation of murine lung carcinoma (3LL).METHODS: The experimental animals were divided into two groups, one is non-implanted Sham and the other is 3LL-implanted group. Samples were collected from six regions of intestinal tract at 28th d after implantation of 3LL cells (1×105 cell/mouse).RESULTS: In this study, five types of immunoreactive (IR) cells were identified except for gastrin and hPP. The regional distributions of the intestinal endocrine cells in the 3LL-implanted group were similar to those of the non-implanted Sham. However, significant decreases of IR cells were detected in 3LL-implanted group compared to those of non-implanted Sham. CGA- and serotonin-IR cells significantly decreased in 3LL-implanted groups compared to that of non-implanted Sham. Somatostatin-IR cells in the jejunum and ileum and CCK-8-IR cells in the jejunum of 3LL-implanted groups significantly decreased compared to that of non-implanted Sham. In addition,glucagon-IR cells were restricted to the ileum and colon of non-implanted Sham.CONCLUSION: Implantation of tumor cell mass (3LL)induced severe quantifiable changes of intestinal endocrine cell density and the abnormality in density of intestinal endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

IMMUNORESPONSES OF HUMANIZED SCID MICE TO HUMAN LUNG CANCER CELLS

HuPBLSCID mice were used to explore how they would response to human tumor cells of 80llMLC.Living 80llMLC cells appeared to be fetal to the the mice due to the production of human TNF- The hupBL-SCID mice did not generate any noticeable amount of specific human immunoglobulin either by single immunization with living 801/MLC cells or by repeated immunization with irradiated 80llMLC cells. Our preliminary experiments with huPBL-SCID mice showed that such chimeras would be a very useful models for tumor immunological researches.

Relationship Between Programmed Death-ligand 1 and Clinicopathological Characteristics in Non-small Cell Lung Cancer Patients

Objective To evaluate the correlation between programmed death-ligand 1 （PD-L1） expression in primary lung cancer cells, tumor associated macrophages （TAM） and patients＇ clinicopathological characteristics. Methods From 2008 to 2010, 208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital, Fudan University. Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM.

新型冠状病毒肺炎中医病理研究

鉴于新型冠状病毒肺炎"病位在肺,属于疫病",其中医名可为"肺疫"。新冠肺疫的病因,外因之主因是感染病毒(异气),内因是患者身体系统,同时合并兼夹感受"六淫"邪气(常气)。只有疫毒本身是普遍的,寒暑燥湿风火不具有普遍性,是因时、因地、因人而变的。常见病机是邪毒犯肺,挟热下利,肺失宣降,水停生湿。总体治则是扶正祛邪、平衡阴阳、标本兼治、三因制宜。此外,本文还提出病毒有无寒热属性的问题,供医学界共同探讨。

A case of interstitial pneumonitis in a patient with ulcerative colitis treated with azathioprine

The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever, cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection, azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.

Choroidal Tuberculoma in an Immunocompetent Young Patient

TUBERCULOSIS （TB） remains one of the leading causes of preventable morbidity and mortality from infectious disease worldwide.1 It is a chronic progressive granulomatous infection caused by Mycobacterium tuberculosis （M. tuberculosis）.

Expression of Angiotensin Ⅱ and Aldosterone in Radiation-induced Lung Injury

Objective Radiation-induced lung injury （RILl） is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILl was studied. Methods Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-[31, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Results Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Conclusions Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

Expression of IL-4 in a rat model of chronic pulmonary infection with biofilm formation induced by Pseudomonas aeruginosa

The expression of IL-4 in a rat model of chronic pulmonary infection biofilm formation induced by Pseudomonas aeruginosa was investigated, in which SPF Wister rats were infected via trachea with 0.1 ml P. aeruginosa strain PAO579 （ 10^9 CFU/ml） in alginate beads or the planktonic form of this bacterial strain （109 CFU/ml）, and on 3, 7 and 14 d after infection, the bacteriological and pathological changes were observed as well as the expression of the cytokine IL-4 was determined. It was demonstrated that the count of CFU per lung tissue in case of bacteria in alginate beads was significantly higher than that of bacteria in planktonic form, with more severe gross pathologic changes and inflammatory reactions in the alginate bead group in comparison with that of the planktonic forms （ P = 0. 002, P = 0. 004 and P = 0. 002, respectively）. In addition, the expression of IL-4 in the alginate bead group was also higher than that in the planktonic form （P = 0.02, P = 0.02 and P = 0.022, respectively）. A positive correlation between the level of IL-4 expression and the gross lung pathology in alginate bead group existed as demonstrated by simple regression analysis （r = 0.78, P 〈 0.02）. It is concluded that the chronic pulmonary infection with biofilm formation induced by P. aeruginosa tends to have the priority to the Th2 immune response.

Lack of Response in Severe Pneumocystis Pneumonia to Combined Caspofungin and Clindamycin Treatment: a Case Report

PNEUMOCYSTIS pneumonia (PCP) is among the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS).Although trimethoprim-sulfamethoxazole (TMP-SMX) is the first line therapy for that condition given its efficacy,approximately one third of patients experienced dose-limiting toxicity.1 For cases of severe to moderate PCP,if TMP-SMX treatment fails or is contraindicated,primaquine combined with clindamycin or intravenous pentamidine is recommended as second line therapy.2 However,both primaquine and pentamidine are associated with severe adverse reactions and often unavailable at hospitals in China.3 As a result,other treatment options have been explored.