The Beneficial Effect of 3-Month-Induction Therapy with Corticosteroids and Mycophenolate Mofetil Followed by Maintenance Therapy with Yearly Rituximab Infusions as Sole Maintenance Therapy in Cryptogenic Chronic Hypersensitivity Pneumonitis

Background: The available data on cryptogenic chronic hypersensitivity pneumonitis (ccHP) indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the role of a new autoimmune regimen in treatment of its severe and progressive disease. Patients and Methods: A total of 9 patients were included in the study. They had criteria for ccHP viz. 1) clinical features of cryptogenic progressive restrictive lung disease, 2) high-resolution computed tomographic pulmonary abnormalities, and 3) bronchoalveolar lavage lymphocytosis (>30%). The regimen consisted of an initial induction phase of 3-month Solumedrol 1 g IV daily for 3 days followed by 1 month of Prednisone (P) 60 mg/day to tapered down to discontinuation by 3rd month. They also had received Mycophenolate mofetil (MMF) 1 g twice daily for 3 months. This stage was followed by a maintenance phase of yearly Rituximab infusions (1 g followed by 1 g 2 weeks later). Results: compared to their previous 6 months deterioration;all patients showed significant improvement in their forced vital volume, diffusion capacity for carbon monoxide, 6-minutes-walk after the induction phase (at 3 months) which improved further at 15 months with Rituximab therapy. Conclusion: After 3-month induction therapy with P and MMF;yearly R treatment is a safe, practical and effective long-term therapy for ccHP.

Rare imaging findings of hypersensitivity pneumonitis:A case report

BACKGROUND Hypersensitivity pneumonitis(HP)is an immune-mediated syndrome caused by allergen inhalation.High-resolution computed tomography(HRCT)of HP may show diffuse ground-glass opacity,centrilobular ground-glass nodules,areas of air-trapping,thin-walled cysts,or fibrotic changes.CASE SUMMARY A 47-year-old male patient went to the hospital complaining of cough and gradual aggravation of shortness of breath.HRCT of the lung showed that multiple nodules and ground-glass high-density shadows were present in both lungs.In addition,circular high-density shadows of various sizes were widely distributed in both lungs with relatively normal lung markings inside them.But other tests did not have a positive finding that can clarify the cause.Therefore,the patient underwent a lung biopsy.The pathological results showed that the lesions tended to be HP.After 4 mo of follow-up,the lesions in the patient's lungs were absorbed spontaneously,and the symptoms of cough and shortness of breath have disappeared.The review results suggested that the patient's disease was self-healing,which was consistent with the characteristics of HP.CONCLUSION For some patients with HP,abnormal HRCT findings,such as the lesions in the lungs,can be absorbed on their own,which is an important clue in the diagnosis of the disease.Early diagnosis by lung biopsy is necessary when antigen exposure is unknown.

Interaction between Primary Care Physicians and Specialists for Diagnosis and Management of Hypersensitivity Pneumonitis

Objective: Hypersensitivity pneumonitis (HP) may be a complex syndrome rather than a single, uniform disease entity. The problems associated with HP treatment include a lack of awareness of primary care procedures and scarcity of recent information regarding HP. The main objective of this study was to investigate the problems in the interaction between primary care physicians and chest specialists. Data source: All available clinical records of cases at the Fukujuji Chest Hospital, Tokyo, between 1994 and 2005, supervised by specialists of a university hospital. Study selection: All cases suspected of HP during the period. Results: Nine cases were excluded because of insufficient records or because they did not satisfy the clinical criteria. Twenty-eight enrolled patients (14 men and 14 women;mean age, 53.0 years) were initially treated for respiratory infections by primary care physicians. The final HP types were summer-type (n = 18), bird fancier’s lung (n = 2), ventilation-related (n = 3), or undetectable antigen (n = 5). On the basis of the interval between the onset of initial symptoms and the time of referral to our hospital, the cases can be categorized into 3 groups, which may represent acute, subacute, and chronic HP. Conclusion: All patients initially received treatment on the basis of a different diagnosis at primary evaluation. We concluded that interaction between primary care physicians and chest specialists is essential for solving problems associated with the early diagnosis and adequate treatment of HP.

Investigation of the cell composition and gene expression in the delayed-type hypersensitivity tuberculin skin test

Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].

Clinical characteristics of hypersensitivity pneumonitis:non-fibrotic and fibrotic subtypes

Background:The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis(HP)guidelines.The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis(NFHP)and fibrotic hypersensitivity pneumonitis(FHP)and explore factors associated with the presence of fibrosis.Methods:In this prospective cohort study,patients diagnosed with HP through a multidisciplinary discussion were enrolled.Collected data included demographic and clinical characteristics,laboratory findings,and radiologic and histopathological features.Logistic regression analyses were performed to explore factors related to the presence of fibrosis.Results:A total of 202 patients with HP were enrolled,including 87(43.1%)NFHP patients and 115(56.9%)FHP patients.Patients with FHP were older and more frequently presented with dyspnea,crackles,and digital clubbing than patients with NFHP.Serum levels of carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 153,gastrin-releasing peptide precursor,squamous cell carcinoma antigen,and antigen cytokeratin 21-1,and count of bronchoalveolar lavage(BAL)eosinophils were higher in the FHP group than in the NFHP group.BAL lymphocytosis was present in both groups,but less pronounced in the FHP group.Multivariable regression analyses revealed that older age,<20%of lymphocyte in BAL,and≥1.75%of eosinophil in BAL were risk factors for the development of FHP.Twelve patients developed adverse outcomes,with a median survival time of 12.5 months,all of whom had FHP.Conclusions:Older age,<20%of lymphocyte in BAL,and≥1.75%of eosinophil in BAL were risk factors associated with the development of FHP.Prognosis of patients with NFHP was better than that of patients with FHP.These results may provide insights into the mechanisms of fibrosis in HP.

Multiple regression analysis of risk factors related to radiation pneumonitis

BACKGROUND Radiation pneumonitis(RP)is a severe complication of thoracic radiotherapy that may lead to dyspnea and lung fibrosis,and negatively affects patients’quality of life.AIM To carry out multiple regression analysis on the influencing factors of radiation pneumonitis.METHODS Records of 234 patients receiving chest radiotherapy in Huzhou Central Hospital(Huzhou,Zhejiang Province,China)from January 2018 to February 2021,and the patients were divided into either a study group or a control group based on the presence of radiation pneumonitis or not.Among them,93 patients with radiation pneumonitis were included in the study group and 141 without radiation pneumonitis were included in the control group.General characteristics,and radiation and imaging examination data of the two groups were collected and compared.Due to the statistical significance observed,multiple regression analysis was performed on age,tumor type,chemotherapy history,forced vital capacity(FVC),forced expiratory volume in the first second(FEV1),carbon monoxide diffusion volume(DLCO),FEV1/FVC ratio,planned target area(PTV),mean lung dose(MLD),total number of radiation fields,percentage of lung tissue in total lung volume(vdose),probability of normal tissue complications(NTCP),and other factors.RESULTS The proportions of patients aged≥60 years and those with the diagnosis of lung cancer and a history of chemotherapy in the study group were higher than those in the control group(P<0.05);FEV1,DLCO,and FEV1/FVC ratio in the study group were lower than those in the control group(P<0.05),while PTV,MLD,total field number,vdose,and NTCP were higher than in the control group(P<0.05).Logistic regression analysis showed that age,lung cancer diagnosis,chemotherapy history,FEV1,FEV1/FVC ratio,PTV,MLD,total number of radiation fields,vdose,and NTCP were risk factors for radiation pneumonitis.CONCLUSION We have identified patient age,type of lung cancer,history of chemotherapy,lung function,and radiotherapy parameters as risk factors for radiation pneumonitis.Comprehensive evaluation and examination should be carried out before radiotherapy to effectively prevent radiation pneumonitis.

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment:A case report

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and has a high mortality.However,the treatment options for advanced HCC are limited to tyrosine kinase inhibitors,such as sorafenib and lenvatinib.Since previous regimens have an insufficient efficacy,the combination therapy of atezolizumab and bevacizumab(Ate/Bev)has been investigated,which showed an improvement in progression-free and overall survival.However,the adverse events of this combination therapy in advanced HCC have not been established.Herein,we report a novel case of an unresectable HCC and acute respiratory distress syndrome(ARDS)after a combination therapy of Ate/Bev.CASE SUMMARY An 82-year-old male visited our outpatient clinic for an incidentally detected liver mass.Liver magnetic resonance imaging and enhanced chest computed tomography(CT)were performed,which showed arterial hyperenhancement with washout in delayed phase suggesting HCC,and a well-defined metastatic solid nodule,respectively.F-18 fluorodeoxyglucose positron emission tomography(PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone,lumbar vertebrae,and femur.Because of the high burden of the intrahepatic tumor,transarterial radioembolization was initially performed;after 37 d,a combination therapy of Ate/Bev was administered.The patient visited the emergency department three days after Ate/Bev treatment complaining of dyspnea.He was diagnosed with severe pneumonitis based on CT.Despite administering oxygen via a high-flow nasal cannula,the P/F ratio was only 74;therefore,the patient was diagnosed with ARDS based on the overall examination results.Low tidal volume with high positive end-expiratory pressure,sedative agents combined with a neuromuscular blocker,and a systemic steroid were promptly applied to manage the ARDS.However,the patient did not recover from the hypoxia and expired 31 h after being admitted.CONCLUSION Clinicians should be aware of severe pneumonitis due to the immune-related adverse events of this combination therapy,and patients should be closely monitored after therapy.

Effect of acetyl-L-carnitine on hypersensitivity in acute recurrent caerulein-induced pancreatitis and microglial activation along the brain’s pain circuitry

BACKGROUND Acute pancreatitis(AP)and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis.The validated caerulein-(CAE)induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study.AIM To determine efficacy of acetyl-L-carnitine(ALC)to reduce pain-related behaviors and brain microglial activation along the pain circuitry in CAE-pancreatitis.METHODS Pancreatitis was induced with 6 hly intraperitoneal(i.p.)injections of CAE(50μg/kg),3 d a week for 6 wk in male C57BL/6J mice.Starting in week 4,mice received either vehicle or ALC until experiment’s end.Mechanical hypersensitivity was assessed with von Frey filaments.Heat hypersensitivity was determined with the hotplate test.Anxiety-like behavior was tested in week 6 using elevated plus maze and open field tests.Microglial activation in brain was quantified histologically by immunostaining for ionized calcium-binding adaptor molecule 1(Iba1).RESULTS Mice with CAE-induced pancreatitis had significantly reduced mechanical withdrawal thresholds and heat response latencies,indicating ongoing pain.Treatment with ALC attenuated inflammation-induced hypersensitivity,but hypersensitivity due to abdominal wall injury caused by repeated intraperitoneal injections persisted.Animals with pancreatitis displayed spontaneous anxiety-like behavior in the elevated plus maze compared to controls.Treatment with ALC resulted in increased numbers of rearing activity events,but time spent in“safety”was not changed.After all the abdominal injections,pancreata were translucent if excised at experiment’s end and opaque if excised on the subsequent day,indicative of spontaneous healing.Post mortem histopathological analysis performed on pancreas sections stained with Sirius Red and Fast Green identified wide-spread fibrosis and acinar cell atrophy in sections from mice with CAE-induced pancreatitis that was not rescued by treatment with ALC.Microglial Iba1 immunostaining was significantly increased in hippocampus,thalamus(intralaminar nuclei),hypothalamus,and amygdala of mice with CAE-induced pancreatitis compared to naïve controls but unchanged in the primary somatosensory cortex compared to naïves.CONCLUSION CAE-induced pancreatitis caused increased pain-related behaviors,pancreatic fibrosis,and brain microglial changes.ALC alleviated CAE-induced mechanical and heat hypersensitivity but not abdominal wall injury-induced hypersensitivity caused by the repeated injections.

浅谈医学术语pneumonia与pneumonitis

根据国际权威工具书查证,作者认为,pneumonia主要用作肺实质病变的疾病名称,而pneumonitis是肺炎疾病潜在问题的一个征象,不特指一种疾病,只是"肺炎"的一个通俗名称,即肺组织炎症的一般性术语。

Occupational fibrotic hypersensitivity pneumonia in a halogen dishes manufacturer:A case report

BACKGROUND Fibrotic hypersensitivity pneumonitis(FHP)is an allergic and diffuse pneumonia caused by repeated inhalation of antigenic substances,and sometimes developed in people working in specific environments.While novel antigens and exposures continued to be described,physicians should maintain a high suspicion of potential exposures.A detailed assessment of the patient's occupational exposures as well as living environment is necessary and complete allergen avoidance is the first and most important step in the management of FHP once the allergens are determined.CASE SUMMARY A 35-year-old female was admitted to the hospital with a cough and breathing difficulties for more than one year.She was a nonsmoker and a manufacturer of halogen dishes,which are characteristic Chinese foods,for 15 years without any protection.High resolution computed tomography of the chest demonstrated an interstitial pneumonia pattern.Pulmonary function examination showed restricted ventilation dysfunction and a significant reduction in dispersion ability.Cell differentiation in bronchoalveolar lavage fluid demonstrated lymphocytosis(70.4%)with an increased lymphocyte CD4/CD8 ratio(0.94).Transbronchial lung biopsy combined with lung puncture pathology showed diffuse uniform alveolar interval thickening,chronic inflammatory cell infiltration,a proliferation of tissue in the bronchial wall fiber and alveolar epithelial follicle degeneration,resulting in fibrosis.CONCLUSION Exposure to spices used for the production of halogen dishes may cause FHP.

Dynamic changes in the radiologic manifestation of a recurrent checkpoint inhibitor related pneumonitis in a non-small cell lung cancer patient:A case report

BACKGROUND As immune checkpoint inhibitors(ICIs)have become widely used in lung cancer treatment,immune-related adverse events(irAEs)warrant sufficient attention.Checkpoint inhibitor-related pneumonitis(CIP)is one of the most concerning adverse events as it is uncommon but life threatening.CASE SUMMARY The patient whose case is reported here experienced three episodes of CIP in a span of 4 mon.Interestingly,the three episodes of CIP involved different regions of the lung separately.Taking these pneumonitis areas together makes nearly a whole lung area.CONCLUSION This case showed that recurrent CIPs may occur repeatedly until the whole lung is involved,suggesting that the follow-up period of CIP should be long enough,and the rechallenge of ICI should be done with due caution.

Experimental treatment of radiation pneumonitis with human umbilical cord mesenchymal stem cells

Objective:To evaluate of the curative effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on rat acute radiation pneumonitis.Methods:Fourty rats were randomly divided into control group,radiation group,stem cell prevention group,stem cell treatment group and prednisone treatment group.All rats except those in the control group were radiated with X ray to establish the acute radiation pneumonitis damage model.The hUC-MSCs cultured in vitro was administrated to the rats of the prevention group via tail vein(1×10~6 cells/kg BW)24 h before the radiation,while the same administration was performed in the rats of the treatment group 24 h after the radiation.After 24 h post the radiation,the rats in tbe radiation group were given 0.4 mL physiological saline,and those in the prednisone group were given 1 mg/kg prednisone.All rats were,observed and executed 72 h after the radiation to defect lung histological changes.Results:After the administration of hUC-MSCs,the survival status of the rats in the prevention group and treatment group was obviously better than that in the control group.As shown by the histological staining,the morphology,proliferation activity aad bronchial state of lung tissues were better in the prevention group and treatment group than in the control group.Conclusion:The hUC-MSCs have definite therapeutic effects on acute radiation pneumonitis in rats.

Radiation pneumonitis after stereotactic radiation therapy for lung cancer

Stereotactic body radiation therapy(SBRT)has a locacontrol rate of 95%at 2 years for non-small cell lungcancer(NSCLC)and should improve the prognosis oinoperable patients,elderly patients,and patients withsignificant comorbidities who have early-stage NSCLCThe safety of SBRT is being confirmed in internationalmulti-institutional PhaseⅡtrials for peripheral lungcancer in both inoperable and operable patients,bureports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer.Radiation pneumonitis(RP)is oneof the most common toxicities of SBRT.Although mospost-treatment RP is Grade 1 or 2 and either asymptomatic or manageable,a few cases are severe,symptomatic,and there is a risk for mortality.The reportedrates of symptomatic RP after SBRT range from 9%to28%.Being able to predict the risk of RP after SBRT isextremely useful in treatment planning.A dose-effecrelationship has been demonstrated,but suggesteddose-volume factors like mean lung dose,lung V20and/or lung V2.5 differed among the reports.We foundthat patients who present with an interstitial pneumo-nitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumo-nitis after SBRT.At our institution,lung cancer patients with these risk factors have not received SBRT since 2006,and our rate of severe RP after SBRT has de-creased significantly since then.

Clinical characteristics and outcomes of hypersensitivity pneumonitis: a population-based study in China

Backgrounds:Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) that develops in response to the inhalation of various antigens. The clinical pathologies are very complex and undetermined. The clinical features and outcomes of HP have not been fully elucidated. The aim of this study was to analyze the incidence, clinical features, and outcomes of HP patients and construct a simple clinical model for diagnosing chronic HP (CHP). Methods: The cohort study included 101 patients with HP admitted to the Nanjing Drum Tower Hospital from January 2009 to December 2017. The patients were categorized into acute HP (AHP, n = 72) and CHP (n = 29) groups according to the updated international criteria. The clinical, imaging, treatment, and follow-up data were retrospectively reviewed. All patients were followed up until December 31,2017. Statistical analysis was performed, and a clinical scoring system for CHP was constructed by SPSS 20.0 software. Results: The incidence of HP was 2.4% in ILD inpatients in our center. Patients in the CHP group were older =-2.212, P = 0.029), had more smokers (x^2 = 8.428, P = 0.004), and longer duration of symptoms (t =-4.852, P < 0.001) than those in the AHP group. Weight loss, crackles, digital clubbing, and cyanosis were more common in the CHP group than those in the AHP group (x^2 = 5.862, P < 0.001;x^2 = 8.997, P = 0.003;x^2 = 11-939, P = 0.001;and x^2 = 4.025, P = 0.045, respectively). On chest high-resolution computed tomography (HRCT), reticular patterns, traction bronchiectasis, and accompanying honeycombing were more common in CHP cases than those in AHP cases (x^2 = 101.000, P < 0.001;x^2 = 32.048, P < 0.001;a n d /2 = 36.568,P < 0.001, respectively). The clinical scoring system for CHP was established based on the clinical variables (age [A], duration of symptoms [D], smoking history [S], unidentified exposure [U], and chest HRCT [C];ADSUC)(area under the curve 0.935, 95% confidence interval: 0.883-0.987, P < 0.001). Eleven patients (15.3%) in the AHP group developed CHP, and unidentified exposure was an independent risk factor for the progression of disease (P = 0.038). The survival of patients with CHP, smoking history, unidentified antigens and fibrosis on Chest HRCT were significantly worse (P = 0.011, P = 0.001, F = 0.005, and P = 0.011, respectively) by Kaplan-Meier analysis. Cox multivariate regression analysis revealed that unidentified exposure and total lung volume (TLC pred%) were independent prognostic predictors for HP patients (P = 0.017 and P = 0.017, respectively). Conclusions: The clinical features and outcomes of the CHP patients differ from those of the AHP patients. ADSUC is a simple and feasible clinical model for CHP. Unidentified exposure is an independent risk factor for the progression of AHP to CHP. Unidentified exposure and a low baseline TLC pred% are independent predictors for survival in HP patients.

Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C

Interstitial pneumonitis(IP) is an uncommon pulmonary complication associated with interferon(IFN) therapy for chronic hepatitis C virus(HCV) infection.Pneumonitis can occur at any stage of HCV treatment,ranging from 2 to 48 wk,usually in the first 12 wk.Its most common symptoms are dyspnoea,dry cough,fever,fatigue,arthralgia or myalgia,and anorexia,which are reversible in most cases after cessation of IFN therapy with a mean subsequent recovery time of 7.5 wk.Bronchoalveolar lavage in combination with chest high resolution computed tomography has a high diagnostic value.Prompt discontinuation of medication is the cornerstone,and corticosteroid therapy may not be essential for patients with mild-moderate pulmonary functional impairment.The severity of pulmonary injury is associated with the rapid development of IP.We suggest that methylprednisolone pulse therapy followed by low dose prednisolone for a short term is necessary to minimize the risk of fatal pulmonary damage if signs of significant pulmonary toxicity occur in earlier stage.Clinicians should be aware of the potential pulmonary complication related to the drug,so that an early and opportune diagnosis can be made.

Potential rat model of anxiety-like gastric hypersensitivity induced by sequential stress

AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.

Fructo-oligosaccharide intensifies visceral hypersensitivity and intestinal inflammation in a stress-induced irritable bowel syndrome mouse model

AIM To determine whether fructo-oligosaccharide(FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids(SCFA) in an irritable bowel syndrome(IBS) mouse model.METHODS Mice were randomly assigned to daily oral gavage of saline solution with or without FOS(8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress(WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field(HPF), respectively.RESULTS Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid(2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid(0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid(0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA(3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin(IL)-23 mR NA(4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mR NA(2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum(12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon(6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS.CONCLUSION FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.

The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients

Immune checkpoint inhibitors(ICIs)are new and promising therapeutic agents for non-small cell lung cancer(NSCLC).However,along with demonstrating remarkable efficacy,ICIs can also trigger immune-related adverse events.Checkpoint inhibitor pneumonitis(CIP)has been reported to have a morbidity rate of 3%to 5%and a mortality rate of 10%to 17%.Moreover,the incidence of CIP in NSCLC is higher than that in other tumor types,reaching 7%to 13%.With the increased use of ICIs in NSCLC,CIP has drawn extensive attention from oncologists and cancer researchers.Identifying high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse events.In this review,the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease,prior thoracic irradiation,and combinations with other drugs.Our review also explored potential mechanisms closely related toCIP,including increasedT cell activity against associated antigens in tumor and normal tissues,preexisting autoantibodies,and inflammatory cytokines.

Hydrocarbon pneumonitis following fuel siphonage: A case report and literature review

BACKGROUND: People sometimes siphon fuel to fill their tanks. However, this is a potentially dangerous procedure and may cause hydrocarbon pneumonitis. We present the case of a patient with severe hydrocarbon pneumonitis after siphoning fuel. The patient underwent artifi cial ventilation and was admitted to hospital for 97 days. METHODS: We review the relevant literature for a better understanding of clinical features and management strategies for hydrocarbon pneumonitis following fuel siphonage.RESULTS: We reviewed 15 articles, which included 3 original articles and 12 case reports that reported the clinical features of fuel siphonage. In addition, we added our presented case for data analysis. A total of 40 cases were included in this review. The literature review found that hydrocarbon pneumonitis caused by fuel siphonage occurs worldwide and that most patients(80%) became symptomatic within 1 day of aspiration. Cough(70%), chest pain(62.5%), dyspnoea(55%), and fever(52.5%) presented in more than half of all patients. The right middle lobe(80%) was the predominantly involved lung fi eld; more than one-third of patients(36.7%) showed the involvement of two lobes.CONCLUSION: Patient history, computed tomographic scans of the chest, and bronchoalveolar lavage are the commonly used diagnostic tools. Supportive care remains the foundation of treatment, whereas antibiotics, steroids, and bronchoalveolar lavage are practical therapies. Patients' clinical improvement precedes the resolution of lesions on chest X-ray. Most complications arise from pulmonary lesions. The prognosis of patients suffering from hydrocarbon pneumonitis following fuel siphonage might be improved by accurate diagnosis and appropriate care.

Effects of electroacupuncture on c-Fos expression in the spinal cord and brain of rats with chronic visceral hypersensitivity

BACKGROUND： Visceral hypersensitivity is the main cause of irritable bowel syndrome, c-Fos is a marker of visceral hypersensitivity in the central nervous system. Electroacupuncture can relieve chronic visceral hypersensitivity in rats, but the mechanism is still unknown. OBJECTIVE： To identify c-Fos expression in the spinal cord and cerebral cortex of rats with chronic visceral hypersensitivity, and to test the effects of electroacupuncture on pain sensitivity in rats with chronic visceral hypersensitivity. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the Animal E：~perimental Center, Shanghai University of Traditional Chinese Medicine, from January to April, 2007. MATERIALS： A total of 24 neonatal, male, Sprague Dawley rats, aged five days old, were equally and randomly assigned into a normal group, a model group, and an electroacupuncture group. Rabbit anti-rat c-Fos antibody and Evision secondary antibody kits （Sigma, USA）, diaminobenzidine kit （Dako, Denmark）, and an LD202H electroacupuncture apparatus （Huawei, Beijing, China） were used in this study. METHODS： Neonatal rats from the model and electroacupuncture groups were used to establish rat models of chronic visceral hypersensitivity by the saccule stimulation method. After model establishment, 0.25 mm diameter electric needles were inserted into Tianshu （ST 25） and Shangjuxu （ST37） at a depth of approximately 0.5 cm, with an square wave （alternating current frequency at 100/20 Hz, amplitude ranged 0.2-0.6 ms, intensity at 1 mA） once for 20 minutes, once a day, for seven days. Rats in the normal and model groups were not treated. MAIN OUTCOME MEASURES： Following 7 days of treatment, c-Fos expression in the spinal cord and cerebral cortex was detected by immunohistochemistry. After the first electroacupuncture treatment, abdominal withdrawal reflex scores were investigated to evaluate the pain threshold for chronic visceral hypersensitivity in rats. RESULTS： Visceral hypersensitivity increased c-Fos staining （P 〈 0.05）, and electroacupuncture significantly decreased the number of these cells to near normal levels （P 〉 0.05）. Abdominal withdrawal reflex scores were significantly lower in the electroacupuncture and normal groups than in the model group （P 〈 0.05） and were similar between the electroacupuncture and normal groups （P 〉 0.05）. CONCLUSION： Electroacupuncture decreases c-Fos expression in the spinal cord and cerebral cortex and increases pain threshold in a chronic visceral hypersensitivity model in rats.