Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Ghrelin is a newly discovered gastrointestinal peptide that is involved in regulating the body's growth,development and energy balance,and plays a key role in the occurrence and progression of malignant tumors,such as cell proliferation,migration,invasion,apoptosis,inflammatory response and vascular disease.Generate immune cell infiltration and so on.Ghrelin affects the progression of gastric cancer by activa-ting NF-κB/p65 and AMPK and other signaling pathways.Ghrelin not only assist in early screening of gastric cancer,but also function a new marker for predicting the prognosis and survival of gastric cancer patients.Ghrelin and its analogs have clinical application value in the treatment of gastric cancer-related syndromes such as cachexia or sarcopenia.

Objective:To explore the effects of nutrition management based on Patient-Generated Subjective Global Assessment (PG-SGA) on nutritional idicators,quality of life and other indicators in patients with pancreatic cancer undergoing chemotherapy, to provide guidance for the implementation of the intervention plan for pancreatic cancer patients undergoing chemotherapy.Methods:This was a randomized controlled study. From January 2021 to December 2022, 96 patients with pancreatic cancer who received chemotherapy in Shanghai Changzheng Hospital and Affiliated Cancer Hospital of Fudan University were selected using convenience sampling method and divided into the observation group and the control group according to the random number table, with 48 cases in each group. The control group was given routine nursing intervention, and the observation group was given PG-SGA-based nutrition management intervention. Patients in both groups continued the intervention until discharge. Nutritional indexes, quality of life, the score of cancer-related fatigue, sleep quality and mental state before and after intervention, intervention compliance and satisfaction after intervention, and complications during intervention of both groups were compared.Results:There were 48 patients in each group ultimately. In the control group, there were 28 males, 20 females, aged (63.33 ± 4.31) years old; in the observation group, there were 27 males, 21 females, aged (63.15 ± 4.25) years old. After intervention, the PG-SGA score, serum triacylglycerol level, and scores of Revised Piper ′s Fatigue Scale and Arsens Insomnia Scale, Self-rating Anxiety Scale and Self-rating Depression Scale in the observation group were (3.87 ± 1.16) points, (1.35 ± 0.52) mmol/L, (3.79 ± 0.67) points, and (5.31 ± 2.05), (44.55 ± 5.14), (45.15 ± 5.08) points respectively, lower than the control group ′s (5.77 ± 1.58) points, (2.04 ± 0.35) mmol/L, (4.82 ± 0.88) points, and (7.29 ± 2.14), (51.74 ± 5.18), (52.26 ± 5.11) points, the differences were statistically significant ( t values were 4.63-7.63, all P<0.05); the serum levels of retinol binding protein and transferrin were (18.13 ± 2.41) mg/L and (61.25 ± 5.34) ng/L, respectively, higher than the control group ′s (15.29 ± 2.33) mg/L and (48.31 ± 5.28) ng/L, with statistical significance ( t=5.87, 11.94, both P<0.05). The symptom domain score in the observation group after intervention was (56.17 ± 5.25) points, lower than (66.22 ± 5.57) points in the control group, while the cognitive, social, emotional, role, and physical scores were (76.35 ± 5.71 ), (77.55 ± 6.51 ), (75.87 ± 6.45), (77.38 ± 6.61), (75.75 ± 6.37) points, higher than (66.29 ± 5.39), (65.74 ± 6.34 ), (64.22 ± 6.18), (66.56 ± 6.26), (65.74 ± 6.11) points in the control group ( t values were 7.86 to 9.10, all P<0.05). Conclusions:Nutritional management based on PG-SGA could reduce the degree of cancer-induced fatigue, relieve negative emotions, improve the overall nutritional status, improve intervention compliance, reduce the occurrence of complications; improve sleep quality, quality of life, and patient ′s satisfaction.

Objective:To investigate the impact of neuroendocrine function on postoperative complications and nutritional status in gastric cancer patients.Methods:Clinical data of 102 gastric cancer patients who underwent radical gastrectomy at the Department of General Surgery, First Affiliated Hospital of Soochow University, from Aug 2021 to Jun 2022 were retrospectively analyzed.Results:Among the 102 gastric cancer patients, 18 (17.6%) suffered from postoperative complications. Univariate analysis indicated that age, BMI, preoperative plasma ghrelin concentration, and preoperative hemoglobin levels were associated with early postoperative complications following radical gastrectomy. Multivariate analysis revealed that age, BMI, and preoperative plasma ghrelin concentration ( P<0.05) were independent risk factors for postoperative complications in gastric cancer patients. Differential analysis of ghrelin concentration demonstrated correlations with hemoglobin levels, skeletal muscle index, albumin, and creatinine, and a positive correlation with the skeletal muscle index. Conclusions:Reduced preoperative neuroendocrine hormone ghrelin concentration is an independent risk factor for postoperative complications in gastric cancer patients. Ghrelin concentration is correlated with the skeletal muscle index in these patients.

BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Objective:To investigate difficult-to-treat sites in patients with psoriasis receiving biological therapy.Methods:Clinical data were retrospectively collected from 73 adult patients with psoriasis in the database of Psoriasis Center, National Clinical Research Center for Skin and Immune Diseases from June 2020 to September 2021, who had received sufficient and standardized treatment with biological agents for ≥ 24 weeks, and were still treated with biological agents at the time of enrolment into this study with the psoriasis area and severity index (PASI) score being 1 - 5 at the time of enrolment into the database of Psoriasis Center. Distribution of psoriatic lesions resistant to biological therapy were analyzed, and differences in refractory sites were compared between different biologics. Chi-square test or Fisher′s exact test was used to analyze differences in the anatomical distribution of residual skin lesions after treatment with different biologics, McNemar test to compare the anatomical distribution of skin lesions before and after biological therapy, and Kruskal-Wallis H test to analyze the association between PASI scores for residual skin lesions and dermatology life quality index (DLQI) scores. Results:After ≥ 24 weeks of sufficient and standardized biological therapy in the 73 patients, refractory skin lesions mostly involved the lower limbs (46 cases, 63.01%) , followed by the scalp (36 cases, 49.32%) and upper limbs (27 cases, 36.99%) ; proportions of patients with residual skin lesions on the face and neck, trunk, upper limbs, lower limbs, hands and feet significantly decreased after biological therapy compared with those before treatment (paired χ2 = 5.14, 7.69, 9.90, 4.17 and 6.13, P = 0.016, 0.003, 0.001, 0.031 and 0.008, respectively) , while there was no significant difference in the proportions of patients with skin lesions on the scalp and genital areas before and after treatment (both P > 0.05) . No significant difference in the anatomical distribution of residual skin lesions was observed between the 13 patients receiving treatment with tumor necrosis factor inhibitors (adalimumab, infliximab, or tumor necrosis factor receptor-antibody fusion protein) and 59 receiving treatment with interleukin-17 (IL-17) inhibitors (secukinumab or ixekizumab) (all P > 0.05) . There was no significant difference in the anatomical distribution of residual skin lesions in the 13 patients before and after the treatment with tumor necrosis factor inhibitors (all P > 0.05) ; in the 59 patients treated with IL-17 inhibitors, the proportions of patients with residual skin lesions on the trunk, upper limbs, hands and feet significantly decreased after treatment (paired χ2 = 4.90, 9.09 and 7.11, P = 0.021, 0.001 and 0.004, respectively) , while there was no significant difference in the distribution of skin lesions on the scalp, face and neck, lower limbs and genital area before and after treatment (all P > 0.05) . Among the 73 patients, the PASI scores for lesions on the upper and lower limbs and the total PASI scores were all associated with the DLQI scores ( H = 7.52, 12.61, 6.75, respectively, all P < 0.05) , and were significantly higher in the patients with DLQI scores of > 10 points than in those with DLQI scores of ≤ 5 points (all P < 0.05) . Conclusions:Biological therapy-resistant psoriatic lesions were mostly located on the scalp, and refractory skin lesions mostly involved the lower limbs, scalp and upper limbs. No significant difference in the anatomical distribution of residual skin lesions was observed between patients treated with tumor necrosis factor inhibitors and IL-17 inhibitors, but IL-17 inhibitors may result in lesion clearance at more anatomical sites compared with tumor necrosis factor inhibitors.

Objective To analyze the changes in morphology of intervertebral foramina in patients with cervical spondylotic radiculopathy (CSR) treated with fixedpoint lateral flexion and rotation manipulation based on three-dimensional (3D) reconstruction technology, so as to provide references for the effectiveness of manipulation treatment. MethodsForty patients with CSR were treated with fixed point lateral flexion and rotation manipulation once every other day for a total of 7 times and 2 weeks as a course of treatment. CT data of the patients before and after treatment were analyzed by using multifunctional CT, Mimics 21.0, Geomagic and SolidWorks 2017. The area of the intervertebral foramen, anterior and posterior diameter of the intervertebral foramen, upper and lower diameter of the intervertebral foramen were measured before and after treatment, as well as the infrared thermal imaging temperature differences of the bilateral neck and shoulder, front and back of the upper limb, and the VAS scores of the patients were observed before treatment, 7 d after treatment, 14 d after treatment and 1 month follow-up. Results Foraminal area, anterior and posterior diameters, upper and lower diameters of 40 patients were improved after treatment, and the temperature differences of infrared thermal imaging of patients before and after treatment were statistically significant. The VAS score of the patients decreased progressively. Conclusions Fixed point lateral flexion manipulation can significantly improve the shape of the intervertebral foramen in patients with CSR, so as to achieve the treatment purpose of relieving nerve compression.

Objective : To investigate the role of endoplasmic reticulum stress in hepatic insulin resistance induced by intermittent hypoxia in rats． Methods : Twenty-four SD rats were randomly divided into control group ( NC group) and intermittent hypoxia group ( CIH group) ．The NC group was placed in a normoxia environment for 12 weeks，and the CIH group was given intermittent hypoxia for 8 weeks，and then returned to normoxia until the 12th week．In both groups，fasting blood glucose (FBG) ，fasting insulin (FINS) ，and liver inositol-requiring enzyme- 1 α(IRE1 α) ，X-box binding protein 1s(XBP1s) ，forkhead box transcription factor O1 (FoxO1) ，activating transcription factor-6(ATF6) ，cAMP-response element binding protein( CREB) ，CREB-regulated transcription coacti- vator-2( CRTC2) ，double-stranded RNA-dependent protein kinase-like ER kinase ( PERK) ，eukaryotic initiation factor 2 α(eIF2 α) ，protein kinase B ( AKT) ，phosphoenolpyruvate carboxykinase ( PEPCK) ，glucose-6-phosphat- ase( G6Pase) mRNA were measured at baseline，week 8，and week 12 . Results : There was no significant differ- ence in each observation index between the two groups at baseline ; at 8 weeks，the levels of FBG，FINS and the mRNA levels of IRE1α , XBP1s，ATF6，PERK，eIF2 α , PEPCK and G6Pase in the CIH group were higher than those in the NC group (P＜0. 05) ，while the mRNA levels of CREB，CRTC2 and AKT were lower than those in the NC group (P＜0. 05) ; at 12 weeks，there was no significant difference in each observation index between the two groups．Pearson correlation analysis showed(8th week of intermittent hypoxia group) : homeostasis model as- sessment-insulin resistance(HOMA-IR) was positively correlated with FoxO1，CREB，CRTC2 and PERK，eIF2 α mRNA levels (r = 0. 172，0. 595，0. 183，0. 702，0. 608 ; P＜0. 05) while it was negatively correlated with IRE1α , XBP1s，ATF6，AKT mRNA levels (r = －0. 422 ，－0. 327 ，－0. 309 ，－0. 399 ; P＜0. 05) ． Conclusion Intermittent hypoxia can lead to insulin resistance，and endoplasmic reticulum stress may mediate this effect.