With the increasing utilization of cancer therapy, the incidence of lung injury associated with these treatments continues to rise. The recognition of pulmonary toxicity related to cancer therapy has become increasingly critical, for which interstitial lung disease (ILD) is a common cause of mortality. Cancer therapy-related ILD (CT-ILD) can result from a variety of treatments including chemotherapy, targeted therapy, immune checkpoint inhibitors, antibody-drug conjugates, and radiotherapy. CT-ILD may progress rapidly and even be life-threatening; therefore, prompt diagnosis and timely treatment are crucial for effective management. This review aims to provide valuable information on the risk factors associated with CT-ILD; elucidate its underlying mechanisms; discuss its clinical features, imaging, and histological manifestations; and emphasize the clinical-related views of its diagnosis. In addition, this review provides an overview of grading, typing, and staging treatment strategies used for the management of CT-ILD.
Humans ; Lung Diseases, Interstitial/diagnosis* ; Neoplasms/therapy* ; Risk Factors ; Immune Checkpoint Inhibitors/adverse effects* ; Antineoplastic Agents/therapeutic use*

This study explored the mechanism of Xiangsha Liujunzi Decoction(XSLJZD) in the treatment of functional dyspepsia(FD) based on inositol-requiring enzyme 1(IRE1)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway-mediated autophagy in interstitial cells of Cajal(ICC). Forty-eight SPF-grade male SD suckling rats were randomly divided into a blank group and a modeling group, and the integrated modeling method(iodoacetamide gavage + disturbance of hunger and satiety + swimming exhaustion) was used to replicate the FD rat model. After the model replications were successfully completed, the rats were divided into a model group, high-dose, medium-dose, and low-dose groups of XSLJZD(12, 6, and 3 g·kg~(-1)·d~(-1)), and a positive drug group(mosapride of 1.35 mg·kg~(-1)·d~(-1)), and the intervention lasted for 14 days. The gastric emptying rate and intestinal propulsion rate of rats in each group were measured. The histopathological changes in the gastric sinus tissue of rats in each group were observed by hematoxylin-eosin(HE) staining. The ultrastructure of ICC was observed by transmission electron microscopy. The immunofluorescence double staining technique was used to detect the protein expression of phospho-IRE1(p-IRE1), TNF receptor associated factors 2(TRAF2), phospho-ASK1(p-ASK1), phospho-JNK(p-JNK), p62, and Beclin1 in ICC of gastric sinus tissue of rats in each group. Western blot was used to detect the related protein expression of gastric sinus tissue of rats in each group. Compared with those in the blank group, the rats in the model group showed decreased body weight, gastric emptying rate, and intestinal propulsion rate, and transmission electron microscopy revealed damage to the endoplasmic reticulum structure and increased autophagosomes in ICC. Immunofluorescence staining revealed that the ICC of gastric sinus tissue showed a significant elevation of p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins and a significant reduction of p62 protein. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. Compared with the model group, the body weight of rats in the high-dose and medium-dose groups of XSLJZD was increased, and the gastric emptying rate and intestinal propulsion rate were increased. Transmission electron microscopy observed amelioration of structural damage to the endoplasmic reticulum of ICC and reduction of autophagosomes, and the p-IRE1, TRAF2, p-ASK1, p-JNK, and Beclin1 proteins in the ICC of gastric sinus tissue were significantly decreased. The p62 protein was significantly increased. Western blot revealed that the expression levels of relevant proteins in gastric sinus tissue were consistent with those of proteins in ICC. XSLJZD can effectively treat FD, and its specific mechanism may be related to the inhibition of the expression of molecules related to the endoplasmic reticulum stress IRE1/ASK1/JNK pathway in ICC and the improvement of autophagy to promote gastric motility in ICC.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Autophagy/drug effects* ; Rats ; Rats, Sprague-Dawley ; Interstitial Cells of Cajal/metabolism* ; Dyspepsia/physiopathology* ; Protein Serine-Threonine Kinases/genetics* ; MAP Kinase Kinase Kinase 5/genetics* ; MAP Kinase Signaling System/drug effects* ; Humans ; Endoribonucleases/genetics* ; Multienzyme Complexes

OBJECTIVES: To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor (MR) and the development of tubulointerstitial nephritis (TIN), and to evaluate the impact of MR on dyslipidemia, particularly secondary hyperlipemia, in patients with diabetic kidney disease. METHODS: We conducted a two-sample Mendelian randomization study using genome-wide association study (GWAS) summary data. Genetic variants associated with MR levels were selected as exposures, with TIN and lipid profiles [including low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol] as outcomes. A two-step Mendelian randomization approach was used to assess TIN as a mediator, employing inverse variance weighted regression as the primary analysis, supplemented by Mendelian randomization-Egger, weighted median, and sensitivity analyses. RESULTS: Cytoplasmic unactivated MR level exhibited a significant causal association with a decreased risk of TIN (OR = 0.8598, 95% CI [0.7775-0.9508], P < 0.001). Although no significant causal relationship was identified between MR level and secondary hyperlipemia, a potential association of cytoplasmic unactivated MR level with lower LDL-C levels was observed (OR = 0.9901, 95% CI [0.9821-0.9983], P = 0.018). Additionally, TIN exhibited causal links with secondary hyperlipemia (OR = 1.0016, 95% CI [1.0002-1.0029], P = 0.020) and elevated LDL-C (OR = 1.0111, 95% CI [1.0024-1.0199], P = 0.012), particularly LDL-C in European males (OR = 1.0230, 95% CI [1.0103-1.0358], P < 0.001). Inverse Mendelian randomization analysis revealed causal relationships between TIN and genetically predicted triglyceride (OR = 0.7027, 95% CI [0.6189-0.7978], P < 0.001), high-density lipoprotein cholesterol (OR = 1.1247, 95% CI [1.0019-1.2626], P = 0.046), and LDL-C (OR = 0.8423, 95% CI [0.7220-0.9827], P = 0.029). Notably, TIN mediated 16.7% of the causal association between MR and LDL-C levels. CONCLUSIONS MR plays a critical role in the development of TIN and lipid metabolism, highlighting the potential of MR-antagonists in reducing renal damage and lipid metabolism-associated complications.
Humans ; Mendelian Randomization Analysis ; Nephritis, Interstitial/metabolism* ; Receptors, Mineralocorticoid/genetics* ; Lipid Metabolism/genetics* ; Genome-Wide Association Study ; Male ; Female ; Polymorphism, Single Nucleotide ; Dyslipidemias/metabolism*

Lung cancer is the cancer with the highest incidence and mortality rate worldwide. In addition to the diversified treatment and prolonged lifespan in view of the development of medical technology, the side effect of medicine should not be ignored. Drug-induced interstitial lung disease (DI-ILD) is also commonly encountered during this process, and ILD triggered by the treatment of lung cancer characterized by the inflammation and scarring of lung tissue after the antitumor treatment in lung cancer leads to a poor prognosis and high mortality. The diagnosis and treatment of ILD caused by anti-lung cancer agents remains challenging in clinical settings and requires joint efforts from multidisciplinary team (MDT). This review systematically updates the epidemiology, molecular pathogenesis, genomics/genetics study, diagnosis and treatment of ILD related to anti-lung cancer agents. By the integration of the latest evidences, the paper offers clinical work references for early diagnosis of ILD related to anti-lung cancer agents to enhance the survival and quality of life of the lung cancer patients.
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Humans ; Lung Diseases, Interstitial/therapy* ; Lung Neoplasms/drug therapy* ; Antineoplastic Agents/therapeutic use*

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare autosomal dominant hereditary disorder characterized by hyperuricemia, gout, impaired urinary concentration, and progressive renal failure. It is primarily caused by mutations in uromodulin (UMOD) gene. This study reports a family with ADTKD in which whole-exome sequencing and Sanger sequencing identified a missense mutation in the UMOD gene, c.761A>C (p.H254P), present in both the proband and affected relatives. According to American College of Medical Genetics and Genomics (ACMG) guidelines, this variant is classified as likely pathogenic. The mutation results in an amino acid substitution that may impair UMOD protein folding and intracellular trafficking. UMOD gene mutations are associated with ADTKD, and genetic testing plays a vital role in the early diagnosis and treatment of this condition, highlighting its importance in the diagnosis of rare kidney diseases.
Adult ; Humans ; Male ; Exome Sequencing ; Mutation ; Mutation, Missense ; Nephritis, Interstitial/genetics* ; Pedigree ; Uromodulin/genetics*

OBJECTIVES: To investigate the therapeutic efficacy and mechanism of pentosan polysulfate (PPS) for cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) in mice. METHODS: Female C57BL/6 mice (6-8 weeks old) were randomized into control group, PPS treatment (25 mg/kg via gavage for 3 weeks) group, CYP treatment (3 separate intraperitoneal injections at 50 mg/kg in week 4), and CYP+PPS treatment group. Gut microbiota alterations of the mice were analyzed using 16S rDNA sequencing and non-targeted metabolomics. Fecal microbiota transplantation (FMT) was performed in CYP-treated recipient mice and those treated with both CYP and PPS. In the in vitro experiment, LPS-stimulated human bladder epithelial cells (SV-HUC-1) were used to assess the effects of deoxycholic acid (DCA) and TGR5 signaling inhibitor SBI-115 on barrier functions of bladder epithelial cells. RESULTS: PPS treatment significantly improved the mechanical pain thresholds, restored the urodynamic parameters, and attenuated bladder inflammation and barrier dysfunction in CYP-treated mice. Mechanistically, PPS enriched the abundance of Eubacterium xylanophilum and increased DCA levels in the intestines of CYP-treated mice. FMT experiments confirmed microbiota-dependent therapeutic effects of PPS, shown by reduced bladder pathology in the recipient mice treated with both CYP and PPS. In SV-HUC-1 cells, DCA obviously alleviated LPS-induced inflammation and barrier disruption, and treatment with SBI-115 abolished these protective effects of DCA. CONCLUSIONS PPS ameliorates IC/BPS in mice by remodeling gut microbiota to enhance DCA production and activate TGR5 signaling, suggesting a novel microbiota-bile acid-TGR5 axis that mediates the therapeutic effect of PPS and a therapeutic strategy for IC/BPS by targeting gut-bladder crosstalk.
Animals ; Cystitis, Interstitial/drug therapy* ; Gastrointestinal Microbiome/drug effects* ; Pentosan Sulfuric Polyester/therapeutic use* ; Cyclophosphamide/adverse effects* ; Mice, Inbred C57BL ; Female ; Mice ; Bile Acids and Salts/metabolism* ; Urinary Bladder ; Fecal Microbiota Transplantation ; Humans

Both carcinoembryonic antigen and CA19-9 are considered as predictive markers of intestinal cancer recurrence and metastasis.In addition,CA19-9 elevation is considered as a predictive marker of connective tissue disease-related interstitial lung disease.The incidence of oxaliplatin and capecitabine-associated interstitial lung disease is low,and there is no report about CA19-9 as a predictive marker of oxaliplatin and capecitabine-associated interstitial lung disease.This paper reports a case of interstitial lung disease with CA19-9 elevation caused by oxaliplatin and capecitabine adjuvant therapy for ileocecal carcinoma.The change trend of serum carcinoembryonic antigen in this patient was consistent with tumor recurrence and metastasis,and that of serum CA19-9 was consistent with the severity of interstitial lung disease.Therefore,CA19-9 elevation after intestinal cancer surgery does not necessarily indicate the tumor recurrence and metastasis,and attention should be paid to the possibility of oxaliplatin and capecitabine-associated interstitial lung disease.
Humans ; CA-19-9 Antigen/blood* ; Capecitabine ; Cecal Neoplasms/drug therapy* ; Chemotherapy, Adjuvant ; Deoxycytidine/administration & dosage* ; Fluorouracil/administration & dosage* ; Lung Diseases, Interstitial/blood* ; Organoplatinum Compounds/administration & dosage* ; Oxaliplatin

INTRODUCTION: Exposure to chemical agents in salon products, such as ammonia and formaldehyde, poses significant respiratory health risks for hairdressers. This study aimed to assess the prevalence of Diffuse Parenchymal Lung Disease Patterns (DPLD) observed in chest X-rays of hairdressers in the National Capital Region and to document their reported respiratory symptoms. METHODS: An analytical, cross-sectional study was conducted involving 100 hairdressers who underwent plain chest X ray examinations to identify any of the 12 recognized DPLD patterns. Participants also accomplished a self administered questionnaire detailing their demographic information, working conditions, health histories and current respiratory symptoms. RESULTS: Thirty nine percent of participants showed DPLD patterns on chest X-rays, primarily fine reticular opacities (69.23%) and coarse reticular opacities (25.64%). Positive associations (RR>1) were linked to over five years of work, lack of PPE, daily exposure to hair iron steam, respiratory symptoms, and salon vapor exposure of exceeding five hours daily. Symptoms reported included shortness of breath (27%) and throat irritation (15%). Logistic regression confirmed a significant link between DPLD and positive respiratory symptoms. CONCLUSION This study highlights the risk of structural lung abnormalities and respiratory symptoms among hairdressers, emphasizing the need for improved workplace safety, consistent PPE use and routine medical screenings to reduce occupational health risks.
Human ; Lung diseases, interstitial

OBJECTIVE: To detect the serum level of chemokine CXC motif chemokine 10 (CXCL-10) and Krebs von den lungen-6 (KL-6) in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD), and to analyze their correlation with RA-ILD, as well as the significance in RA-ILD. METHODS: A total of 169 RA patients were enrolled in the study. According to imaging findings of with and without ILD in high-resolution computed tomography scans of chest, the subjects were divided into RA-ILD group and RA-non-ILD group. According to the inclusion and exclusion criteria, 80 patients in each of the two groups were finally selected. Two groups were matched according to the 1 ∶ 1 ratio using propensity score matching (PSM). The serum CXCL-10 and KL-6 levels were detected by enzyme-linked immunosorbent assay. The clinical features, laboratory data and medications between the two groups were compared after PSM and the correlation between serum levels and clinical parameters were analyzed. Binary Logistic regression was used to analyze the risk factors of ILD in the RA patients, and the predictive value of CXCL-10 and KL-6 in RA-ILD was evaluated. RESULTS: In this study, 49 patients with RA-ILD and 49 patients with RA-non-ILD were selected by PSM. The levels of CXCL-10 and KL-6 in the RA-ILD group [64.36 (34.01, 110.18) ng/L, 360.70 (236.35, 715.05) U/mL] were significantly higher than those in the RA-non-ILD group [29.80 (16.89, 40.55) ng/L, 210.69 (159.98, 255.50) U/mL] (all P < 0.001). The results of correlation analysis showed that the level of serum CXCL-10 was positively correlated with the Warrick score on chest CT (r=0.378, P=0.007) and negatively correlated with the percentage of forced vital capacity to the predicted value (FVC%, r=-0.338, P=0.018). And the level of KL-6 was positively correlated with rheumatoid factor (RF, r=0.296, P=0.039) and negatively correlated with FVC% (r=-0.436, P=0.002) and the percentage of diffusion capacity for carbon monoxide to the predicted value (DLCO%, r=-0.426, P=0.002). Both univariate and multivariate Logistic regression analysis showed that CXCL-10 and KL-6 were positively correlated with ILD, the values of OR were 1.035 and 1.023 in CXCL-10 and those were 1.004 and 1.005 in KL-6 respectively (P < 0.05). The ROC curves were plotted with CXCL-10 and KL-6. The area under the curve (AUC) was 0.770 and 0.752 respectively. The AUC of combined detection increased to 0.800. CONCLUSION Serum levels of CXCL-10 and KL-6 are significantly elevated in patients with RA-ILD and correlated with the severity of ILD. The combined estimate of them helps to improve the effectiveness of diagnosis.
Humans ; Lung Diseases, Interstitial/etiology* ; Arthritis, Rheumatoid/complications* ; Chemokine CXCL10/blood* ; Mucin-1/blood* ; Female ; Male ; Tomography, X-Ray Computed ; Risk Factors ; Middle Aged

OBJECTIVE: To investigate the clinical and immunological characteristics of anti-synthetase syndrome (ASS) patients overlap with rheumatoid arthritis (RA). METHODS: A retrospective analysis was conducted on ASS patients with arthritis who were treated at Peking University People' s Hospital. Data collected included demographic information, clinical manifestations, laboratory features, lymphocyte subsets in peripheral blood, and treatments. The patients with ASS were divided into two groups based on the presence or absence of RA for comparative analysis. RESULTS: A total of 104 ASS patients with arthritis were included, among whom 23.1% (24/104) were diagnosed with RA. The ASS with RA group had a significantly higher incidence of rapidly progressive interstitial lung disease (RP-ILD) (41.7% vs. 17.6%, P=0.032), number of tender joints [10 (7, 14) vs. 4 (0, 8), P < 0.001], number of swollen joints [4 (2, 8) vs. 2 (0, 4), P=0.012], and rate of bone erosion (47.8% vs. 2.5%, P < 0.001) compared with the non-RA group. Levels of platelets [(289.57±68.74)×10³/μL vs. (247.94±77.04)×10³/μL, P=0.022], erythrocyte sedimentation rate (ESR) [43 (19, 59) mm/h vs. 18 (10, 44) mm/h, P=0.019], and C-reactive protein (CRP) [19.20 (4.80, 55.36) mg/L vs. 5.68 (1.10, 14.96) mg/L, P=0.006] were found significantly higher in the ASS with RA group than those in non-RA group. Analysis of immune cells in peripheral blood mononuclear cell (PBMC) showed that significantly decreased proportions of CLA⁺ Treg cells [(11.12±4.10)% vs. (17.22±8.49)%, P=0.003], B cells [8.56% (4.80%, 11.90%) vs. 14.55% (8.75%, 20.29%), P=0.025], and natural killer (NK) cells [7.56% (4.65%, 13.20%) vs. 13.25% (7.46%, 19.25%), P=0.045] in the overlap group compared with non-RA group. Proportion of Naïve Th cells [(52.66±17.66)% vs. (40.76±14.96)%, P=0.033)] was significantly increased in overlap group compared with non-RA group. Overlap group had lower rate of complete clinical response than non-RA group (16.7% vs. 43.8%, P=0.031). CONCLUSION Among ASS patients with arthritis, those with RA have more severe lung and joint involvement and a lower treatment response rate, highlighting the need for early recognition and aggressive intervention.
Humans ; Arthritis, Rheumatoid/immunology* ; Retrospective Studies ; Lung Diseases, Interstitial/immunology* ; Male ; Myositis/blood* ; Female ; Middle Aged ; Autoantibodies/blood*