Prevalence of and associated factors for sarcopenia in patients with liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is associated with poor outcomes in patients with cirrhosis. However, the prevalence of and associated factors for developing sarcopenia in this population remain to be determined. OBJECTIVES: This study aimed to summarize the prevalence, characteristics, and associated factors of sarcopenia in patients with cirrhosis. METHODS: Electronic searches were performed from inception to June 9, 2022 to identify the eligible studies. We meta-analyzed the prevalence of sarcopenia in overall patients with cirrhosis and subgroups. Both crude and adjusted odds ratios (ORs) were pooled using the random effects model. RESULTS: A total of 55 studies involving 13,158 patients from 17 countries were included. The overall prevalence of sarcopenia was 40.1 % (95 % CI 35.4%-44.9 %) in patients with cirrhosis. The pooled prevalence was higher in males, Child-Pugh class C cirrhosis, decompensated stage, ascites, subjective global assessment class C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index) at a higher cutoff. In multivariate analysis, older age (adjusted OR 1.04, 95 % CI 1.00-1.07), male (adjusted OR 4.75, 95 % CI 2.72-8.28), lower body mass index (BMI) (adjusted OR 0.78, 95 % CI 0.73-0.83), alcoholic liver disease (ALD) (adjusted OR 1.43, 95 % CI 1.19-1.72), but not ascites and hepatic encephalopathy, were significantly associated with an increased risk of sarcopenia in patients with cirrhosis. CONCLUSION: Sarcopenia is a prevalent complication, and older age, male patients, lower BMI, and patients with ALD are associated with an increased risk of sarcopenia in patients with cirrhosis.

Non-acid reflux and esophageal dysmotility is associated with early esophageal squamous cell carcinoma.

BACKGROUND: Studies have demonstrated that non-acid reflux (NAR) is associated with esophageal squamous cell carcinoma (ESCC). Esophageal dysmotility is associated with NAR but few studies have focused on the esophageal motility of ESCC patients. We explored the relationship between ESCC, NAR and esophageal dysmotility with the aid of multichannel intraluminal impedance and pH (MII-pH) and high-resolution manometry (HRM). METHODS: From Jan 2021 to Oct 2022, 20 patients with superficial ESCC were enrolled as the ESCC group, while 20 age and gender matched individuals without gastroesophageal reflux disease (GERD) symptoms and 20 age and gender matched patients with GERD symptoms were recruited as the control groups. Patients received 24 h MII-pH and HRM procedure before endoscopic submucosal dissection (ESD), and the data were then collected to identify the type of reflux and esophageal dysmotility. RESULTS: Prevalence of esophageal dysmotility was significantly different among the three groups, 75.0% in the ESCC group, 35.0% in the non-GERD group and 70.0% in the GERD group (P = 0.029). NAR episodes at 15 cm above the lower esophageal sphincter (LES) in the ESCC group were significantly higher than that in the non-GERD group (6.5 (3.5-9.3) vs 1.0 (0.8-4.0), P = 0.001) and were similar with that in the GERD group (6.5 (3.5-9.3) vs 5.5 (3.0-10.5), P > 0.05). NAR episodes at 5 cm above LES was significantly higher in the ESCC group than that in the non-GERD group (38.0 (27.0-60.0) vs 18.0 (11.8-25.8), P = 0.001) and was significantly higher than that in the GERD group (38.0 (27.0-60.0) vs 20.0 (9.8-30.5)), P = 0.010). Prevalence of pathologic non-acid reflux was significantly different among the three groups, 30.0% in the ESCC group, 0.0% in the non-GERD group and 10.0% in the GERD group (P < 0.001). CONCLUSION: Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200061456.

Loss of FGFR3 Accelerates Bone Marrow Suppression-Induced Hematopoietic Stem and Progenitor Cell Expansion by Activating FGFR1-ELK1-Cyclin D1 Signaling.

Patients with chemotherapy or radiation therapy often generate anemia and low immunity due to the therapy-induced bone marrow (BM) suppression. To enhance hematopoietic regeneration during the therapy-induced BM suppression urgently need to be solved. Fibroblast growth factors (FGFs) play important regulatory roles in hematopoietic stem and progenitor cell (HSPC) expansion in vitro and in vivo by the FGF receptor (FGFR1-4)-mediated signaling pathway. FGFR3 is an important member of the FGFR family, and its regulatory function in hematopoiesis is largely unknown. Using knockout (KO) mice of FGFR3, we found that loss of FGFR3 does not affect HSPC functions or lineage differentiation during steady-state hematopoiesis, but FGFR3 deletion accelerates HSPC expansion and hematopoiesis recovery via a cell-autonomous manner under 5-fluorouracil-induced BM suppression. Our results showed that FGFR3 inactivation accelerates BM suppression-induced HSPC expansion by upregulating FGFR1 and its downstream transcriptional factor, ELK, which regulates the expression of the cyclin D1 gene at the level of transcription. Further studies confirmed that loss of FGFR3 in hematopoietic cells inhibits in vivo leukemogenesis under BM suppression. Our data found a novel hematopoietic regulatory mechanism by which FGFR3 deletion promotes HSPC expansion under BM suppression and also provided a promising approach to enhance antileukemia and hematopoietic regeneration by inhibiting FGFR3 functions in HSPCs combined with leukemic chemotherapy.

Loss of FGFR3 Delays Acute Myeloid Leukemogenesis by Programming Weakly Pathogenic CD117-Positive Leukemia Stem-Like Cells.

Chemotherapeutic patients with leukemia often relapse and produce drug resistance due to the existence of leukemia stem cells (LSCs). Fibroblast growth factor receptor 3 (FGFR3) signaling mediates the drug resistance of LSCs in chronic myeloid leukemia (CML). However, the function of FGFR3 in acute myeloid leukemia (AML) is less understood. Here, we identified that the loss of FGFR3 reprograms MLL-AF9 (MA)-driven murine AML cells into weakly pathogenic CD117-positive leukemia stem-like cells by activating the FGFR1-ERG signaling pathway. FGFR3 deletion significantly inhibits AML cells engraftment in vivo and extends the survival time of leukemic mice. FGFR3 deletion sharply decreased the expression of chemokines and the prolonged survival time in mice receiving FGFR3-deficient MA cells could be neutralized by overexpression of CCL3. Here we firstly found that FGFR3 had a novel regulatory mechanism for the stemness of LSCs in AML, and provided a promising anti-leukemia approach by interrupting FGFR3.

Construction and characterization of immunoliposomes targeting fibroblast growth factor receptor 3.

Fibroblast growth factor receptor 3 (FGFR3) plays an important regulatory role in tumor cell proliferation and drug resistance. FGFR3 is often constitutively active in many tumors. To deliver drugs into tumor cells by targeting FGFR3 will be a promising and potential strategy for cancer therapy. In this study, a novel fusion protein, ScFv-Cys containing a single chain variable fragment (ScFv) and an additional C-terminal cysteine residue, was generated at a rate of 10 mg/L of bacterial culture and purified at 95% by Ni-NTA chromatography. Subsequently, the recombinant ScFv-Cys was coupled with malPEG2000-DSPE and incorporated into liposomes to generate the immunoliposomes. The results indicated that immunoliposomes can specifically deliver the fluorescent molecules, Dio into bladder cancer cells highly expressing FGFR3. In conclusion, we successfully generated FGFR3-specific immunoliposomes, and proved its targeting effect and delivering ability.