Preliminary studies on the effect of excretory secretory (ES) Ascaris lumbricoides antigens on colorectal cell line viability.

Helminth parasites are a group of complex metazoans from various taxonomic families. Excretory secretory (ES) by-products, secreted by living parasites from the surface, appeared to modulate the host immunological response towards helminth infection. This study aims to investigate the effect of ES antigen from helminth parasite on colorectal cell viability. Worm were cultured in phosphate-buffered saline (PBS x1) at 37°C for 24 hours after being rinsed in sterile PBS. Using a mortar and pestle, the worm was crushed vigorously using PBS. The obtained excretory secretory (ES) antigens were extracted and filtered using a 0.22 µM filter and stored at -20°C for further assay. For LCMS, 100 µl of the extract was analysed using Agilent ZORBAX Eclipse Plus C18 Rapid Resolution HT. The extraction of ES antigen (10 µg/ml and 20 µg/ml) was used for cell viability studies using CRC cell line HCT 116. Cell viability and MTT assay were conducted as per the protocol mentioned in the MTT kit. The liquid chromatography and mass spectrometry (LCMS) data indicated that the ES antigen contained metabolic compounds, namely fatty acid, amino alcohol, indoles, sterols, glycosides, and sphingoids. For the Ascaris lumbricoides LCMS analyses, around 405 metabolic peaks were detected. Out of which, 58 were detected via the database were identified, while several compounds detected have anticancer properties. The MTT assay indicated that after 24 hours and 48 hours of exposure, all treated cells showed a decrease in cell viability compared to the control group. The preliminary studies demonstrated that the ES antigen from Ascaris lumbricoides has some ability to decrease the cell viability of the HCT116 CRC cell line. Further studies are needed to examine the cell cycle arrest and apoptosis effect of the ES antigen towards the CRC cell line.

[Aqueous extract of Chuan Xiong Rhizoma enhances inhibitory effect of temozolomide against brain metastasis of melanoma in mice].

OBJECTIVE: To investigate the effect of the aqueous extract of Chuan Xiong Rhizoma (CR) on brain metastasis of melanoma B16F10 cells in mice. METHODS: C57BL/6J mouse models of brain metastasis of melanoma were established by ultrasound-guided intraventricular injection of Luc-labeled B16F10 cells, and brain tumor growth was monitored by in vivo imaging. The mouse models were then randomized for daily gavage of saline or aqueous extract of CR (equivalent crude drug concentration of 1 mg/g). Behavioral tests were used to evaluate the neuroprotective effects of CR in the tumor-bearing mice, and the changes in proteins associated with blood-brain barrier integrity, neuronal cell proliferation and apoptosis, and microglial cell apoptosis and activation were observed using immunofluorescence assay. The efficacy of CR combined with temozolomide (25 mg/kg) against brain metastases of B16F10 cells was observed by in vivo imaging. RESULTS: CR-treated mouse models did not show obvious progression of brain metastases and had a reduced rate of body weight loss and lowered protein expressions of ZO-1, claudin-5, occludin, P-gp, TNF-α, AQP4 and PDGFRß. In the behavioral tests, the CR-treated mice showed prolonged stay on the wooden stick with a shortened time of sticky stick removal. Immunofluorescence assay showed increased proliferation and decreased apoptosis of neuronal cells and microglia in CR-treated mice. CR treatment significantly increased the levels of CD86, CD206, IL-4 and IL-10 and decreased the levels of CD163 and IL-1ß in the microenvironment of brain metastases. The mice receiving combined treatments with CR and temozolomide showed significantly lower intensity of fluorescent signals in the brain than those treated with temozolomide alone. CONCLUSION: CR does not promote brain metastasis of melanoma while inducing opening of the blood-brain barrier, and its combined use with TMZ results in enhanced inhibition against brain metastasis of melanoma B16F10 cells in mice.

[Retrospective clinicopathological analysis of pulmonary light chain deposition disease secondary to Sjögren's syndrome].

Objective: To analyze of the clinical, imaging, and pathological features of pulmonary light chain deposition disease(PLCDD) secondary to Sjögren's syndrome(SS), and to improve the understanding of the disease. Methods: We retrospectively analyzed the clinical data of 23 PLCDD cases diagnosed by pathology in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2009 to 2023, a total of 11 cases of PLCDD secondary to SS(SS-PLCDD) were selected, the median age was 51 years old(range:36~74),10 female and 1 male, the clinical, imaging, and pathological features were summarized. Results: All 11 cases showed bilateral multiple pulmonary nodules on HRCT with 10 cases accompanied by cysts, 6 cases with vessels in the cystic wall or crossing the cysts. Microscopically, all 11 cases showed amorphous eosinophilic material with negative Congo red staining deposited in the lung, vascular involvement was common, with variable lymphocyte, plasma cell infiltration and multinucleated giant cell reaction, cysts formation was observed in 6 cases,1 case combined with pulmonary lymphoma. No extrapulmonary involvement in all 11 cases. Ten patients were treated with glucocorticoid and (or) immunosuppressants, 1 patient changed to bortezomib-dexamethasone chemotherapy after 1 year, with a mean follow-up of 50 months, 5 cases were stable on clinical and (or) HRCT findings, 2 cases showed remission on HRCT, 2 cases progressed on HRCT. Conclusions: SS-PLCDD affects predominantly middle-aged females with lesions confined to the lung; HRCT showed bilateral multiple nodules and thin-walled cysts. Pulmonary pathology presented as non-amyloid material with negative Congo red staining and interstitial changes associated with SS. The overall prognosis was good, but caution is advised regarding the underlying lymphoma.

Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

[Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF)].

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

[A case of bilateral corneal ulcer after left eye cataract extraction surgery].

The patient is a 73-year-old female who developed bilateral corneal ulcers one month after cataract surgery in her left eye. The diagnosis is bilateral conjunctival pemphigoid. She underwent a left-eye amniotic membrane transplant and a right-eye lamellar corneal transplant, and was treated with oral immunosuppressants. The patient's condition is stable.

[AZD9291 suppresses proliferation and migration of nasopharyngeal carcinoma cells by inhibiting the PI3K-AKT-mTOR pathway].

OBJECTIVE: To investigate the effects of AZD9291 on the proliferation and migration of nasopharyngeal carcinoma cells. METHODS: Nasopharyngeal carcinoma HNE1 and CNE2Z cells were treated with AZD9291 at the doses of 0.5, 1, 2, 4, and 8 µmol/L and at the doses of 1, 2, 4, 8, and 16 µmol/L, respectively. Cell survival was measured using CCK8 assay, and proliferation inhibition of the cells after AZD9291 treatment was examined with colony-forming assay; the cell repair and migration abilities were determined using scratch assay and Transwell experiment. The expressions of EGFR-related signaling proteins and migration-related proteins were detected using Western blotting. RESULTS: The results of CCK8 assay and colonyforming assay showed that AZD9291 significantly inhibited the viability and proliferation of both HNE1 and CNE2Z cells (P < 0.01). AZD9291 treatment also attenuated the migration ability of HNE1 and CNE2Z cells (P < 0.01). Western blotting showed that, as the concentration of AZD9291 increased, the expression levels of the proteins involved in the PI3K-AKT-mTOR signaling pathway were lowered progressively (P < 0.01), resulting in inhibition of migration of HNE1 and CNE2Z cells (P < 0.01). CONCLUSION: AZD9291 suppresses proliferation and attenuates repair and migration capacities of nasopharyngeal carcinoma cells by inhibiting the EGFR/PI3K/AKT/mTOR signaling pathway, suggesting the potential value of AZD9291 in the treatment of nasopharyngeal carcinoma.

[Analysis of clinical features and the outcome of in-hospital mortality of myocardial infarction with non-obstructive coronary arteries].

Objective: To compare the clinical features and the outcome of in-hospital mortality between patients with myocardial infarction with non-obstructive coronary arteries(MINOCA)and myocardial infarction with obstructive coronary artery disease (MI-CAD). Methods: This is a retrospective study. The clinical data of acute myocardial infarction (AMI) patients admitted to Qilu Hospital of Shandong University from January 2017 to May 2021, who underwent coronary angiography, were collected. Patients were divided into MINOCA group and MI-CAD group according to the degree of coronary stenosis (<50% or ≥50%). Baseline clinical characteristics, electrocardiograph during hospitalization, myocardial bridge, length of stay in hospital, discharge medication and the outcome of in-hospital mortality were collected and compared between the two groups. Univariate and multivariate logistic regression analysis was used to screen the related factors of MINOCA and the factors predicting the nosocomial death outcome of patients with AMI. Results: A total of 3 048 AMI patients were enrolled, age was 62 (54, 69) years, 741 (24.3%) patients were women including 165 patients (5.4%) in the MINOCA group and 2 883 patients (94.6%) in the MI-CAD group. Compared with MI-CAD patients, MINOCA patients were younger, had a higher proportion of females and a higher incidence of NSTEMI, and had a lower history of smoking, diabetes, coronary heart disease and myocardial infarction. Baseline inflammatory markers such as neutrophil count, monocyte count, neutrophil count/lymphocyte count (NLR), and monocyte count/high-density lipoprotein count (MHR) were lower, creatinine, N-terminal pro-brain B-type Natriuretic peptides (NT-proBNP), creatine kinase-MB, hypersensitive troponin I, fibrinogen, baseline blood glucose levels were lower, high-density lipoprotein cholesterol was higher, and the incidence of myocardial bridge, arrhythmia, tachycardia and atrial fibrillation was higher (P<0.05). The application rates of calcium antagonists and non-vitamin K antagonists oral anticoagulants were higher in MINOCA group (P<0.05), and there was no statistical difference in hospitalization days and in-hospital death between the two groups (P>0.05). Multiple logistic regression analysis showed that young age, female, non-smoker, no history of coronary heart disease and low MHR were risk factors of MINOCA (P<0.05). MINCOA was not associated with higher in-hospital death (P>0.05). Patients with AMI and a history of coronary heart disease, chronic renal failure, higher baseline blood glucose, higher NLR, and higher D-dimer were risk factors of in-hospital death (P<0.05). Conclusions: Compared with MI-CAD patients, MINOCA patients are younger, more likely to be female and non-smokers and on history of coronary heart disease, and have lower baseline MHR. MINOCA is often associated with myocardial bridge and atrial fibrillation. The incidence of in-hospital death in MINCOA patients is similar as in MI-CAD patients.

Tumor microenvironment and its clinicopathological and prognostic associations in surgically resected cutaneous angiosarcoma.

PURPOSE: Cutaneous angiosarcoma (CAS) is a rare but typically aggressive malignant vascular neoplasm of the skin. Tumor microenvironment (TME) of CAS and its associations with baseline clinicopathological features and patient outcomes are very important, especially when considering the recent advances in understanding of the tumor biology. METHODS/PATIENTS: We retrospectively reviewed medical records of patients who underwent surgical resection for CAS at a tertiary Hospital. The pretreated specimens were evaluated by immunohistochemistry for programmed cell death protein 1 (PD-1) and its ligand (PD-L1), densities of tumor infiltrative lymphocytes (TILs) (CD3+, CD4+, CD8+, CD45RO+, FoxP3+), as well as c-MYC and Ki-67 expressions. Overall survival (OS) was estimated by Kaplan-Meier method and compared with Log-rank test. RESULTS: A total of 21 CAS patients were identified. Median age was 67 (ranges: 20-81) years, 14 (66.7%) were male, and over 50% had lesions of scalp. Histopathological examination showed a predominantly spindle cell type (57.1%). All patients underwent surgery, 16 (76.2%) were treated further. PD-L1 was positively stained (> 1%) in tumor cells (42.9%) and TILs (23.8%). PD-1 expression (> 1%) was identified in TILs of 11 (52.4%) cases. PD-1/PD-L1 expressions were significantly associated with the higher densities of CD3+, CD4+, CD8+, CD45RO+, and Foxp3+ TILs, but not with patient characteristics or c-MYC or Ki-67 expression. Median OS was 18.5 months (95% CI 6.0-35.9), although no prognostic significance was observed with respect to any clinicopathological features. CONCLUSION: We characterized TME and its clinical and prognostic association in CAS. PD-1/PD-L1 expressions were significantly associated with TILs subtypes but not with OS.

[Chuanxiong Rhizoma inhibits brain metastasis of lung cancer through multiple active ingredients acting on multiple targets, pathways and biological functions].

OBJECTIVE: To explore the molecular mechanism mediating the inhibitory effect of Chuanxiong Rhizoma against brain metastasis of lung cancer using network pharmacology methods and molecular docking. METHODS: The chemical components of Chuanxiong Rhizoma and their targets were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The relevant targets for brain metastasis of lung cancer were screened using the GeneCards database. Clusterpro-filerR package was used to perform GO and KEGG enrichment analysis. Cytoscape and STRING database were used to construct the "active ingredient-target-disease" network and protein-protein interaction (PPI) network of Chuanxiong Rhizoma. The core components of Chuanxiong Rhizoma and their targets in the treatment of lung cancer brain metastasis were screened based on the topological parameters, and the results were verified using molecular docking and in Chuanxiong extract- treated human lung cancer PC9 cells by detecting the core target with Western blotting. RESULTS: Forty-eight active ingredients of Chuanxiong Rhizoma including (Z)-ligustilide, butylphthalide, oleic acid, and myricetone were screened, which target 49 proteins including INS, BDNF, FOS, VEGFA, PTGS2, ESR1, MAPK14, and PTGS1. These proteins participated in 57 biological functions such as nuclear receptor activity, ligand activation, and transcription factor activity, involving 40 signaling pathways such as prolactin signaling pathway, breast cancer, and etrogen signaling. The results of molecular docking showed that myricetone, butylphthalide, 4-hydroxy-3 butylphthalide, (Z)-ligustilide, and ligustalide-E, among others, had strong affinities to 7 cores targets including BDNF, FOS, PTGS2, and MAPK14. In PC9 cells, treatment with Chuanxiong Rhizoma extract resulted in significant reductions in the phosphorylation levels of PI3K, Akt and VEGF (P < 0.01). CONCLUSION: Chuanxiong Rhizoma contains multiple active ingredients against brain metastasis lung cancer, and these ingredients act on multiple targets involving multiple signal pathways and biological functions.

EGFR tyrosine kinase inhibitor Almonertinib induces apoptosis and autophagy mediated by reactive oxygen species in non-small cell lung cancer cells.

Almonertinib, a new third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is highly selective to EGFR T790M-mutant non-small cell lung cancer (NSCLC). However, there is no available information on the form and molecular mechanism of Almonertinib-induced death in NSCLC cells. Herein, CCK-8 and colony formation assays, flow cytometry, electron microscopy, and western blots assay showed that Almonertinib inhibited NSCLC cells growth and proliferation by inducing apoptosis and autophagy which can be inhibited by a broad spectrum of caspase inhibitor Z-VAD-fmk or autophagy inhibitor chloroquine. Importantly, Almonertinib-induced autophagy was cytoprotective in NSCLC cells, and the blockade of autophagy improved cell apoptosis. In addition, Almonertinib increased reactive oxygen species (ROS) generation and clearance of ROS through pretreatment with N-acetyl-L-cysteine (NAC) inhibited the decrease of cell viability, apoptosis and increase of LC3-II induced by Almonertinib. The results of Western blot showed that both EGFR activity and downstream signaling pathways were inhibited by Almonertinib. Taken together, these findings indicated that Almonertinib induced apoptosis and autophagy by promoting ROS production in NSCLC cells.

Comparison of long non-coding RNAs in adipose and muscle tissues between seven indigenous Chinese and the Yorkshire pig breeds.

lncRNAs play crucial roles in fat metabolism in animals. Previously, we have compared the mRNA transcriptome profiles between seven fat-type Chinese pig breeds and one lean-type Western breed (Yorkshire, YY). The associations between differentially expressed (DE) genes and phenotypical traits were investigated. In the present study, to further explore the underlying regulatory mechanisms, lncRNAs were sequenced and compared between YY and Chinese indigenous breeds. The results showed 9114 and 7538 DE lncRNAs between at least one Chinese breed and the YY breed in the adipose and muscle tissue respectively. KEGG enrichment analysis revealed that the target genes of these DE lncRNAs mainly influenced the glucolipid metabolism, which is an important process affecting meat quality. Correlation analyses between the DE lncRNA and DE mRNA genes related to meat quality and growth traits were performed. The results showed that LTCONS_00073280 was associated with intramuscular fat content. Four lncRNAs (LTCONS_00101781, LTCONS_00037879, LTCONS_00088260 and LTCONS-00128343) might mediate backfat thickness. Overall, this study provides candidate lncRNAs that potentially affect meat quality, which might be useful for molecular breeding of pig breeds in future.

[Development and functional validation of a nano-delivery system of miR-16/polypeptide targeting ovarian cancer cells].

OBJECTIVE: To develop a nano-delivery system for targeted delivery of miR-16/polypeptide for enhancing cisplatin sensitivity of ovarian cancer. OBJECTIVE: R9-SS-R9 and cRGD-R9-SS-R9 peptides were synthesized and self-assembled with miR-16 molecules to form a nano-delivery system. The stability, particle size, potential and morphology of the nanoparticles were determined by agarose gel electrophoresis, particle size potentiometer and transmission electron microscopy. CCK-8 assay was used to assess the toxicity of the polypeptides in ovarian cancer cells. Stem loop qRT-PCR and living cell imaging were used to verify the uptake efficiency and intracellular distribution of the nanoparticles. Flow cytometry and Western blotting were performed to verify the effect of the nanoparticles for enhancing cisplatin sensitivity of ovarian cancer cells and explore the possible mechanism. OBJECTIVE: R9-SS-R9/miR-16 and cRGD-R9-SS-R9/miR-16 nanoparticles were successfully prepared. The nanoparticles, with a particle size below 150 nm, a dispersity index less than 0.1 and a potential of about 40 mV, showed a good serum stability. The polypeptide material had no obvious cytotoxicity. The miR-16/polypeptide nanoparticles could be efficiently absorbed by human ovarian cancer cells and were distributed in the cytoplasm. The nanoparticles significantly increased the intracellular expression level of miR-16 (P < 0.001) and decreased the expression of Bcl-2 and Chk-1 proteins in ovarian cancer cells, thus enabling miR-16 to promote apoptosis and enhance cisplatin sensitivity of the cells. OBJECTIVE: We successfully prepared a miR-16/polypeptide nano-delivery system for targeted delivery of miR-16 to ovarian cancer cells for enhancing cisplatin sensitivity of the cancer cells.

[Hypersensitivity pneumonia diagnosed by excisional lung biopsy: a clinicopathological features of 47 cases].

Objective: To analyze the clinicopathological and immunohistochemical characteristics of the hypersensitivity pneumonia (HP) cases that were diagnosed by excisional lung biopsy, to improve the diagnosis accuracy of HP. Methods: The data of 47 HP cases diagnosed by excisional lung biopsy during the last 20 years were collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2000 to June 2020. The clinicopathological features and the immunohistochemical profiles of CD3, CD4, CD8 and CD20 were analyzed using light microscopy and immunohistochemical stains. Results: The age of the patients ranged from 15 to 68 years, while the ratio of male to female was 22∶25. The main symptoms were shortness of breath and cough, and 32 cases had a history of allergen exposure. Most of the patients had restrictive impaired ventilatory function, and impaired diffusion function. The proportion of lymphocytes in bronchoalveolar lavage fluid (BALF) increased in 85.3%(29/34) of the patients, and the CD4+/CD8+ T cell ratio was not higher than 0.8 in 31.3%(10/32) of the patients. Microscopically, 59.6%(28/47) of the cases showed nonnecrotizing granuloma/giant cells in the stroma, and 40.4% (19/47) of the cases had only giant cells. Ninety-three-point six percent of the cases(44/47) had peribronchiolar metaplasia, while 70.2%(33/47) had focal cell-rich inflammation. Forty-four cases (93.6%, 44/47) had fibrosis, which was manifested as usual interstitial pneumonia-like fibrosis (47.7%, 21 cases), nonspecific interstitial pneumonia-like fibrosis (29.5%, 13 cases), purely peribronchiolar fibrosis (6.8%, 3 cases) and mixed fibrosis (15.9%, 7 cases). Immunohistochemistry showed that CD4+ T cells were fewer than CD8+ T cells in 24 cases (55.8%, 24/43) of HP. Thirty-two HP patients had follow-up data. Among them, 7 patients had improved symptoms, 12 patients were stable, and 13 patients had worsening symptoms. Conclusions: The most common type of HP diagnosed by excisional lung biopsy is chronic HP. The clinical characteristics are long course of disease, restricted ventilation disorder and impaired diffusion function with the increase of lymphocyte proportion in BALF. Nearly 1/3 of the patients have no known history of allergen contact. The degree of fibrosis in HP patients diagnosed by excisional lung biopsy is severe, and the histologic types of fibrosis varies, but the UIP-like and/or NSIP-like fibrosis is most common. The CD4+/CD8+ T cell ratio in lung tissues is less than 1 in more than half of the cases. Pulmonary fibrosis continued to increase in some of the patients with chronic HP, even after treatment.

Acupuncture for menopausal symptoms in Chinese women: a systematic review.

Menopause-related symptoms are common problems of middle-aged women that can seriously affect their quality of life. Menopausal hormone therapy (MHT) for climacteric symptoms is the first choice recommended by the International Menopause Society and likewise by other societies and institutions covering this field. However, non-hormonal therapies can be an alternative effective option, especially for women who are not suitable for MHT. Acupuncture is one of the most important methods. With deepening experience of the use of traditional Chinese acupuncture and moxibustion in the improvement of menopause symptoms, more clinical evidence has been obtained to support the effectiveness and safety of this treatment concept that is very often used in China. This review summarizes the evidence for effective treatment of climacteric complaints by acupuncture in recent years, shares the clinical experience of the authors of this review, all of whom head or work in units with daily large numbers of outpatients, and includes, in particular, results from studies performed in the Department of Acupuncture--Moxibustion of Tsinghua University Chuiyangliu Hospital, Beijing, China. In addition, there is a summary about the safety of acupuncture treatment in traditional Chinese medicine.

Twofold improved tumor-to-brain contrast using a novel T1 relaxation-enhanced steady-state (T1RESS) MRI technique.

A technique that provides more accurate cancer detection would be of great value. Toward this end, we developed T1 relaxation-enhanced steady-state (T1RESS), a novel magnetic resonance imaging (MRI) pulse sequence that enables the flexible modulation of T1 weighting and provides the unique feature that intravascular signals can be toggled on and off in contrast-enhanced scans. T1RESS makes it possible to effectively use an MRI technique with improved signal-to-noise ratio efficiency for cancer imaging. In a proof-of-concept study, "dark blood" unbalanced T1RESS provided a twofold improvement in tumor-to-brain contrast compared with standard techniques, whereas balanced T1RESS greatly enhanced vascular detail. In conclusion, T1RESS represents a new MRI technique with substantial potential value for cancer imaging, along with a broad range of other clinical applications.

[The application of next-generation sequencing in the diagnosis of Pneumocystis pneumonia in non-HIV infected patients].

Objective: To evaluate the clinical value of next-generation sequencing in the diagnosis of Pneumocystis pneumonia in non-HIV infected patients. Methods: A retrospective study was conducted on the diagnosis and treatment of Pneumocystis pneumonia in 5 non-HIV patients in the Fourth Medical Center of the General Hospital of the PLA from September 1, 2017 to September 1, 2018. Next-generation sequencing of BALF were compared with the traditional laboratory microbiological test, and the advantages of the next-generation sequencing in the diagnosis of Pneumocystis pneumonia in non-HIV infected patients were analyzed. Results: There were 3 males and 2 females, with a mean age (48±6) years. Three patients had membranous nephropathy, a patient had tuberculous meningitis, and a patient had esophageal cancer after radiotherapy and chemotherapy. All patients had glucocorticoid medication history before. The clinical manifestations were fever, cough and dyspnea. The chest CT mainly showed bilateral lung ground glass shadows. All the results of 1, 3-ß-D-glucan test were more than 1 000 ng/L. Bronchoalveolar lavage was performed in the 5 cases, and Pneumocystis cysts were found in 1 BALF by Gomori's methenamine silver nitrate staining, and the DNAs of Pneumocystis and human herpesvirus were detected in 5 BALFs by next-generation sequencing. All patients were treated with sulfamethoxazole/trimethoprim (orally, 1.44 g, q8 h) for 23 to 72 days (median 33 days), and with ganciclovir(Ⅳ, 250 mg q12 h) for 6 to 22 days (median 15 days). The chest CT manifestations and symptoms were improved after treatment, without death. Conclusions: The next-generation sequencing of BALF is more specific and sensitive in the diagnosis of Pneumocystis pneumoniae in non-HIV patients. It is faster, more comprehensive and more accurate than the traditional laboratory test, and could be widely used as a PCP diagnosis technique.

[Different viral doses of cytomegalovirus infection in the left and right colons].

Objective: To compare the differences in the detection rates of cytomegalovirus (CMV) infection between the left and right colons for guiding endoscopic biopsy-sites. Methods: The cases of colonic CMV infection confirmed by histology at the Peking Union Medical College Hospital from July 2015 to July 2018 were collected and analyzed. Splenic curvature was used as the dividing point between the left and right colons. The CMV inclusions were identified histologically, and the CMV infected cells were detected using immunohistochemistry (EnVision method). The numbers of infected cells in the left and right colons were compared by histological and immunohistochemical results. A total of 731 patients were identified. Ten of the 731 patients had histological specimens of both left and right colons and were confirmed with CMV EnVision immunohistochemical study. There were 25 biopsy or resection specimens. Seven patients were male and 3 were female, and their ages ranged from 29 to 66 years, with a median age of 55 years. All of the 10 patients were also diagnosed with ulcerative colitis. Results: The number of the cells infected with CMV in the left colon was 115 (1-41), while that in the right colon was 76 (0-51). In 8/10 cases, the number of CMV infected cells in the left colon was more than that in the right colon. Conclusions: The study on the biopsies and resection specimens suggests that CMV infection is mostly present in the left colon. The left colon thus might be an important endoscopic biopsy-site for the cases with suspicion of CMV infection.

[Specifications for diagnosis and treatment of non-neonatal tetanus].

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate is still 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.

Associations of serum magnesium levels and calcium-magnesium ratios with mortality in patients with coronary artery disease.

AIMS: Low magnesium (Mg) and high calcium (Ca) levels are linked to increased cardiovascular disease (CVD) risk in the general population. This prospective study assessed whether there are any independent associations of serum Mg levels and Ca-Mg ratios with mortality in patients with coronary artery disease (CAD). METHODS: This prospective cohort study included 3380 CAD patients. Cox regression models were used to estimate associations of serum Mg and Ca-Mg ratio with risk of mortality. RESULTS: A total of 562 deaths (331 due to CVD) were recorded during a 7.59-year (median) follow-up. Spline plots displayed U-shaped associations between serum Mg levels and Ca-Mg ratios and risk of mortality. When compared with a moderate group, adjusted hazard ratios (95% confidence intervals) for low Mg levels and high Ca-Mg ratios were 1.59 (1.30-1.95) and 1.31 (1.06-1.61) for all-cause mortality, and 1.71 (1.32-2.22) and 1.44 (1.09-1.89) for CVD mortality, respectively. There was also a tendency to increase risk of mortality in patients with high serum Mg levels and low Ca-Mg ratios. Associations of low serum Mg and high Ca-Mg ratio with risk of mortality did not change when stratified by gender, body mass index, CAD type, estimated glomerular filtration rate, use of diuretics, or history of diabetes or hypertension. CONCLUSION: This study demonstrated that a moderate Ca-Mg ratio (range: 3.91-4.70) had the lowest mortality risk, and that low serum Mg and high Ca-Mg ratio were independent risk factors of mortality in CAD patients. Nevertheless, the optimal dose-response of Mg and Ca for mitigating CAD risk still requires further investigation.