Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Background Silicosis, caused by inhalation of silica (SiO₂) dust, remains the most prevalent occupational pneumoconiosis in China. While galectin-3 (Gal-3) is known to play pro-inflammatory and pro-fibrotic roles in various diseases, its specific mechanism in the pathogenesis of silicosis has not been fully clarified. Objective To investigate the role and underlying mechanisms of Gal-3 in silicosis using clinical samples of silicosis and a silicosis mouse model. Methods Lung nodule biopsy samples were collected from patients with stage III pneumoconiosis. Concurrently a silicosis mouse model was constructed via non-exposed tracheal intubation with instillation of a SiO₂ suspension. The expression levels of Gal-3 mRNA and protein in the lung tissues of the silicosis model mice were then detected using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. Single-cell transcriptomic sequencing (scRNA-seq) was performed on both human and murine lung samples to analyze the expression of the Gal-3-encoding gene Lgals3 across different cell types. In vitro, RAW264.7 macrophages were treated with varying concentrations of SiO₂ suspension for 24 h and 48 h; the expression levels of Gal-3 mRNA and protein were measured by RT-qPCR and Western blot. The Gal-3 inhibitor TD139 was used to intervene in the SiO₂-induced in vitro macrophage model, and Western blot was used to detect the intracellular expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). Finally, mouse embryonic lung fibroblasts NIH/3T3 and Mlg2908 were treated with varying concentrations of recombinant mouse Gal-3 protein (rmGal-3) for 48 h, and Western blot was used to detect the expression of fibrosis markers [(Collagen I, Collagen III, Fibronectin, and α smooth muscle actin (α-SMA)] and proteins associated with the TGF-β1/Smads signaling pathway. Results RT-qPCR and IHC staining showed that both the gene and protein expression levels of Gal-3 were significantly elevated at all consecutive time points in the silicosis mouse model (P < 0.05). scRNA-seq revealed that Lgals3 was aberrantly highly expressed in lung tissues from pneumoconiosis patients and silicosis mouse models, with the highest expression observed in macrophages. After treatment of macrophages with different concentrations of SiO₂ for 24 h and 48 h, the mRNA and protein expression levels of Gal-3 were significantly upregulated compared with the control group (P < 0.05). Following TD139 intervention, the protein expression levels of IL-1β, TNF-α, and TGF-β1 in dust-exposed macrophages were markedly downregulated (P < 0.0001). After 48 h of stimulation with rmGal-3, the protein expression levels of Collagen I, Fibronectin, and α-SMA in mouse embryonic lung fibroblasts (NIH/3T3 and Mlg2908) were significantly increased in all treatment groups compared with the control group (P < 0.01). Moreover, Gal-3 treatment markedly upregulated TGF-β1 protein expression in Mlg2908 cells and enhanced the phosphorylation levels of Smad2 and Smad3 (P < 0.0001). Conclusion Gal-3 is abnormally expressed in silicotic lung tissues, which primarily originates from macrophages, and inhibition of Gal-3 suppresses SiO₂-induced inflammatory and pro-fibrotic responses. In addition, Gal-3 promotes fibroblast differentiation and extracellular matrix production by activating the TGF-β1/Smads signaling pathway.

Based on the theory of "one qi circulation" founded by HUANG Yuanyu， the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward， which leads to the turbidity assemble in large intestine， forming the carcinoma toxin， and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi， Huangya Decoction （黄芽汤） as the basic formula， the circulation of qi ascending and descending as the base， adjusting ascending and descending together with Xiaqi Decoction （下气汤）， and differentiating the syndrome on yin-yang excess-deficiency； for spleen-kidney yang deficiency syndrome， treated with Tianhun Decoction （天魂汤） to supplement liver， kidney and assist yang； for liver-kidney yin deficiency syndrome， treated wtih Dipo Decoction （地魄汤） to supplement lung， kidney， and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53)， P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Middle Aged ; Female ; Lung Neoplasms/pathology* ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Chemotherapy, Adjuvant ; Patient Reported Outcome Measures ; Quality of Life ; Aged ; Postoperative Period ; Prospective Studies

Objective: To evaluate the diagnostic value and application of 24 h multichannel intraluminal impedance-pH (24 h MII-pH) monitoring in children with gastroesophageal reflux disease (GERD). Methods: This is a cross-sectional study. From January 2013 to December, 2020, 417 patients who received 24 h MII-pH monitoring in Department of Gastroenterology of Children's Hospital Capital Institute of Pediatrics were included. According to results, these children were divided into the GERD and non-GERD groups. Furthermore, the 132 children with GERD who had gastroscopy were divided into the reflux esophagitis (RE) and non-erosive reflux disease (NE) groups to investigate the differences in their refluxes. Non-parametric Mann-Whitney U test or indepentent sample t test was used for comparisons between the groups. Results: Among the 417 children, 232 were males and 185 females, aged (7.3±3.9) years. The course of disease was 0.5 (0.1, 2.0) years. The main clinical symptoms included acid reflux (128 cases), vomiting (173 cases), abdominal pain (101 cases), and cough (76 cases). The 24 h MII-pH monitoring were positive in 243 children (58.3%, 243/417), which was higher than that by 24 h esophageal pH monitoring (43.6%, 182/417). The 24 h MII-pH monitoring results demonstrated significant differences in the episodes of acid reflux, weakly acidic reflux, non-acidic reflux, liquid reflux and mixed reflux between GERD and non-GERD groups (10 (4, 19) vs. 4 (1, 9) times/24 h, 14 (6, 32) vs. 7 (3, 13) times/24 h, 0 (0, 0) vs. 0 (0, 0) times/24 h, 19 (10, 34) vs. 8 (3, 14) times/24 h, and 6 (2, 12) vs. 3 (1, 5) times/24 h, Z=-6.96, -7.25, -5.62, -8.75, and -6.48, all P<0.05, respectively). Besides, the results also showed significant differences in Boix-Ochoa score, episodes of long reflux, course of long reflux, and episodes of weakly acidic reflux between the RE and NE groups (51.2 (21.4, 153.2) vs. 20.7 (12.1, 34.7), 5 (2, 10) vs. 1 (0, 4) times/24 h, 19 (7, 87) vs. 8 (3, 22) min, and 5 (2, 15) vs. 15 (6, 33) times/24 h, Z=-3.44, -3.41, -2.65, and -2.27, all P<0.05, respectively). Conclusion: 24 h MII-pH monitoring not only improves the detection rate of GERD in children, but also provides a possibility to early etiological diagnosis.
Female ; Male ; Humans ; Child ; Cross-Sectional Studies ; Electric Impedance ; Gastroesophageal Reflux/diagnosis* ; Esophageal pH Monitoring ; Hydrogen-Ion Concentration

Objective:To explore the clinical characteristics of adult-onset non-radiographic axial spondyloarthritis (nr-axSpA) in different genders.Methods:A total of 662 patients with adult-onset nr-axSpA (age at disease onset ≥16 years) who visited the Rheumatology Department of the First Affiliated Hospital of Shantou University Medical College from 1999 to 2020 were included in the study. Comparisons of baseline demographic and clinical characteristics between different genders were performed.Results:Overall, the male-to-female ratio was 1.17∶1, and the prevalence of human leukocyte antigen-B27 (HLA-B27) positivity was 71.8%(475/662). The median baseline disease duration and age at diagnosis was 1.6 (0.5, 4.0) years and 25.0 (21.0, 33.0) years respectively. The males had a significantly earlier age at disease onset and diagnosis [21.0 (18.0, 28.0) vs 25.0 (21.0, 30.0), Z=5.63, P<0.001; 24.0 (19.0, 32.0) vs 27.0 (23.0, 34.5), Z=4.90, P<0.001, respectively] than females. HLA-B27 positivity was more frequent in males than in females [78.4% (280/357) vs 63.9%(195/305), χ2=17.06, P<0.001]. The prevalence of inflammatory back pain (IBP), morning stiffness, nocturnal pain, enthesitis, hip and groin pain were higher in males, whereas females showed a higher prevalence of small joint involvement of the hands. At baseline, males had higher median ankylosing spondylitis disease activity score (ASDAS)-C-reaction protein (CRP) [3.0(2.3, 3.8) vs 2.4(2.0, 3.0), Z=5.59, P<0.001] and a greater prevalence of high disease activity ASDAS-CRP>2.1 [81.9%(185/227) vs 67.9%(133/195), χ2=11.08, P=0.001] than females. The proportions of male patients with elevated CRP levels and erythrocyte sedimentation rate (ESR) were also higher than those of female patients [49.0%(175/357) vs 27.9%(85/305), χ2=30.85, P<0.001; 49.3%(176/357) vs 33.4%(102/305), χ2=16.98, P<0.001, respectively]. Conclusion:The adult-onset nr-axSpA in China is characterized by a comparable sex ratio. Males have an earlier age at disease onset and are higher HLA-B27 positivity with higher prevalence of IBP, enthesitis, hip and groin pain, as well as high disease activity.

ObjectiveTo investigate the mechanism of Chaihu Qinggantang （CHQGT） in the treatment of granulomatous lobular mastitis （GLM） in the rat model. MethodSixty female rats were divided into a normal group， a model group， a prednisolone group （0.001 8 g·kg^-1）， and three CHQGT low-dose， medium-dose， and high-dose groups （4.5， 8.9， 17.8 g·kg^-1）. The tissue homogenates mixed with GLM lesion tissue and Fritner's reagent were used for modeling. After modeling， the treatment groups were given corresponding treatment factors， and the normal group and the model group were given the equal volume of normal saline. The changes in mammary gland of rats were observed after 14 d. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in breast samples. The mRNA expressions of NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， Caspase-1， and interleukin-1β （IL-1β） were detected by real-time quantitative fluorescence polymerase chain reaction （Real-time PCR）. The protein expressions of NLRP3， Caspase-1， IL-1β， and IL-18 were detected by Western bolt. ResultAs compared with the normal group， the breasts of rats in the model group were obviously swelling， and mammary gland inflammation index was significantly increased （P<0.01）. Pathological changes included the formation of granuloma centered on the lobule of mammary gland with a large number of inflammatory cells such as lymphocytes and plasma cells. The mRNA expressions of NLRP3， Caspase-1， and IL-1β， and the protein expressions of NLRP3， Caspase-1， IL-1β， and IL18 in the model group were significantly increased （P<0.01）. Compared with the model group， the treatment groups improved breast swelling， and the CHQGT medium and high-dose groups and the prednisolone group reduced inflammation index to some extent after treatment （P<0.05， P<0.01）. The inflammation degree of mammary gland was significantly improved， and inflammatory cells such as macrophages， lymphocytes， and plasma cells were reduced to varying degrees in pathological aspects. The mRNA expressions of NLRP3， Caspase-1， and IL-1β， and the protein expressions of NLRP3， Caspase-1， IL-1β， and IL-18 in the CHQGT high-dose group and the prednisolone group were significantly down-regulated （P<0.05， P<0.01）. ConclusionCHQGT inhibits inflammation and treats GLM in rats. The mechanism is possibly related to the inhibition of NLRP3/IL-1β signaling pathway， which provides a new target for the prevention and treatment of GLM by Qingxiao method.

Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-κB/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1β（IL-1β） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（P<0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（P<0.05，P<0.01）. The uterine organ ratio were decreased significantly（P<0.01），while the ovarian organ ratio were significantly increased（P<0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（P<0.01）.The relative expression levels of inflammation-related protein IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein signaling pathway were significantly increased（P<0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（P<0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（P<0.05，P<0.01）. The uterine organ ratio were increased（P<0.05），while the ovarian organ ratio were decreased（P<0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（P<0.01）. The expression levels of IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein in the high dose group were significantly decreased（P<0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-κB/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．