OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

Objective: To investigate the clinicopathological characteristics of occupational lung diseases, to reduce the missed diagnoses and misdiagnoses of the diseases and to help standardize the diagnosis and treatment of these patients. Methods: A total of 4 813 lung biopsy specimens (including 1 935 consultation cases) collected at the Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China from January 1st, 2017 to December 31th, 2019 were retrospectively analyzed. Among them, 126 cases of occupational lung diseases were confirmed with clinical-radiological-pathological diagnosis. Special staining, PCR and scanning electron microscopy were also used to rule out the major differential diagnoses. Results: The 126 patients with occupational lung diseases included 102 males and 24 females. All of them had a history of exposure to occupational risk factor(s). Morphologically, 68.3% (86/126) of the cases mainly showed pulmonary fibrotic nodules, dust plaque formation or carbon end deposition in pulmonary parenchyma. 16.7% (21/126) of the cases mainly showed welding smoke particle deposition in the alveolar cavity and lung interstitium while 15.1% (19/126) of the cases showed granulomas with fibrous tissue hyperplasia, alveolar protein deposition or giant cell interstitial pneumonia. The qualitative and semi-quantitative analyses of residual dust components in the lung under scanning electron microscope were helpful for the diagnosis of welder's pneumoconiosis and hard metal lung disease. Conclusions: The morphological characteristics of lung biopsy tissue are important reference basis for the clinicopathological diagnosis and differential diagnosis of occupational lung diseases. Recognizing the characteristic morphology and proper use of auxiliary examination are the key to an accurate diagnosis of occupational lung diseases on biopsy specimens.
Male ; Female ; Humans ; Retrospective Studies ; Pneumoconiosis/pathology* ; Lung/pathology* ; Dust ; Pneumonia, Viral/pathology* ; Biopsy

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.
Adenocarcinoma of Lung/drug therapy* ; Adrenocorticotropic Hormone/therapeutic use* ; Aged ; B7-H1 Antigen/therapeutic use* ; Humans ; Hydrocortisone/therapeutic use* ; Hyponatremia/drug therapy* ; Hypopituitarism/drug therapy* ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Male ; Methylprednisolone/therapeutic use* ; Middle Aged ; Nausea/drug therapy* ; Pituitary Gland/pathology* ; Pneumonia ; Prednisone/therapeutic use* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Prolactin/therapeutic use*

Objective: To analyze the clinical characteristics and prognosis of 6 children with idiopathic interstitial pneumonia (IIP). Methods: This retrospective study analyzed the clinical manifestations, examinations, treatment and prognosis of 6 children with IIP who were hospitalized in Children's Hospital of Nanjing Medical University from January 2015 to March 2020. Results: Of the 6 children, 2 were males and 4 were females, aged 4.8 to10.6 years. All children had a subacute onset, and presented with cough, shortness of breath and cyanosis. The lung high-resolution CT (HRCT) showed diffuse patchiness in bilateral lung fields in all the children and reticular pattern in 2 cases. Pulmonary function test found moderate to severe mixed defect in 5 children. Lung biopsy was performed in 4 children. All of the 6 children were treated with systemic glucocorticoids, of whom 2 cases had additional inhaled glucocorticoids. Four children were finally diagnosed as cryptogenic organizing pneumonia (COP), whose lung HRCT return to normal in 1-11 months. Two children were finally diagnosed as nonspecific interstitial pneumonia (NSIP), and had long-term residual fibrosis on lung HRCT. The 6 children were followed up for 1 year to 6 years and 5 months after discontinuation of systemic glucocorticoids, and all had no recurrence. Conclusions: The clinical characteristics of IIP in children are subacute onset presented with cough, shortness of breath, cyanosis and diffuse patchiness in bilateral lungs on HRCT. The common subtypes of IIP in children are COP and NSIP. Systemic glucocorticoid is effective for IIP in children and there is a good prognosis overall.
Child ; Cough/etiology* ; Cryptogenic Organizing Pneumonia ; Cyanosis/pathology* ; Dyspnea/pathology* ; Female ; Glucocorticoids/therapeutic use* ; Humans ; Idiopathic Interstitial Pneumonias/pathology* ; Lung/pathology* ; Male ; Retrospective Studies

Adult ; Body Temperature/drug effects* ; COVID-19/pathology* ; Drug Therapy, Combination ; Drugs, Chinese Herbal/therapeutic use* ; Ephedra sinica/chemistry* ; Female ; Fever/pathology* ; Glycyrrhiza/chemistry* ; Humans ; Indoles/administration & dosage* ; Male ; Medicine, Chinese Traditional/methods* ; Middle Aged ; Phytotherapy/methods* ; Pneumonia, Viral/pathology* ; Radiography, Thoracic ; SARS-CoV-2/drug effects*

Betacoronavirus ; China ; Coronavirus Infections ; Humans ; Pandemics ; Pathology ; organization & administration ; Pneumonia, Viral

Adaptation, Physiological ; Adenosine Monophosphate ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Administration, Intranasal ; Alanine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Betacoronavirus ; genetics ; physiology ; Chlorocebus aethiops ; Coronavirus Infections ; drug therapy ; virology ; Disease Models, Animal ; Female ; Host Specificity ; genetics ; Lung ; pathology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation, Missense ; Nasal Mucosa ; virology ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; RNA, Viral ; administration & dosage ; genetics ; Turbinates ; virology ; Vero Cells ; Viral Load ; Virus Replication

Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load

The coronavirus disease 2019 (COVID-19) is a new infectious disease, which has a strong virus transmission power and complex transmission routes. This disease is prone to outbreak of cluster infection. It is difficult for medical workers to provide a better perioperative treatment for surgery patient with COVID-19 while avoiding hospital spread effectively. The perioperative management for such patients needs to fully consider the possible lung injury factors caused by anesthesia and surgery. It also needs to choose the suitable timing of the operation, carry out preoperative infection screening and evaluation, and implement lung protection strategies during and after the operation to avoid aggravating the lung injury. Meanwhile, it is necessary to pay more attention to infection prevention and control in order to avoid nosocomial infection.
Betacoronavirus ; Coronavirus Infections ; therapy ; Cross Infection ; prevention & control ; Humans ; Lung ; pathology ; virology ; Pandemics ; Perioperative Care ; Pneumonia, Viral ; therapy

Betacoronavirus ; Clinical Protocols ; Coronavirus Infections ; diagnosis ; epidemiology ; pathology ; therapy ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; diagnosis ; epidemiology ; pathology ; therapy